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Sample records for sustained inflammatory response

  1. Sustainable responsibilities?

    DEFF Research Database (Denmark)

    Lystbæk, Christian Tang

    2015-01-01

    This working paper analyzes the conceptions of corporate responsibility for sustainable development in EU policies on CSR. The notion of corporate responsibility has until recently been limited to economical and legal responsibilities. Based on this narrow conception of corporate responsibility.......e. a combination of destruction and construction, this chapter will deconstruct conceptions of responsibility for sustainable development in these EU documents on CSR. A deconstructive conceptual analysis involves destructing dominant interpretations of a text and allowing for constructions of alternative...... such as sustainability actually means, but on what the concept says and does not say. A deconstructive analysis of EU policies on CSR, then, pinpoints that such policies are sites of conceptual struggles. This kind of analysis is suitable for studying conceptions of corporate responsibility for sustainable development...

  2. Common Variants of TLR1 Associate with Organ Dysfunction and Sustained Pro-Inflammatory Responses during Sepsis

    Science.gov (United States)

    Pino-Yanes, Maria; Corrales, Almudena; Casula, Milena; Blanco, Jesús; Muriel, Arturo; Espinosa, Elena; García-Bello, Miguel; Torres, Antoni; Ferrer, Miguel; Zavala, Elizabeth

    2010-01-01

    Background Toll-like receptors (TLRs) are critical components for host pathogen recognition and variants in genes participating in this response influence susceptibility to infections. Recently, TLR1 gene polymorphisms have been found correlated with whole blood hyper-inflammatory responses to pathogen-associated molecules and associated with sepsis-associated multiorgan dysfunction and acute lung injury (ALI). We examined the association of common variants of TLR1 gene with sepsis-derived complications in an independent study and with serum levels for four inflammatory biomarkers among septic patients. Methodology/Principal Findings Seven tagging single nucleotide polymorphisms of the TLR1 gene were genotyped in samples from a prospective multicenter case-only study of patients with severe sepsis admitted into a network of intensive care units followed for disease severity. Interleukin (IL)-1β, IL-6, IL-10, and C-reactive protein (CRP) serum levels were measured at study entry, at 48 h and at 7th day. Alleles -7202G and 248Ser, and the 248Ser-602Ile haplotype were associated with circulatory dysfunction among severe septic patients (0.001≤p≤0.022), and with reduced IL-10 (0.012≤p≤0.047) and elevated CRP (0.011≤p≤0.036) serum levels during the first week of sepsis development. Additionally, the -7202GG genotype was found to be associated with hospital mortality (p = 0.017) and ALI (p = 0.050) in a combined analysis with European Americans, suggesting common risk effects among studies. Conclusions/Significance These results partially replicate and extend previous findings, supporting that variants of TLR1 gene are determinants of severe complications during sepsis. PMID:21048935

  3. Inflammatory response in equine joints

    OpenAIRE

    Ley, Cecilia

    2010-01-01

    Proinflammatory cytokines mediate inflammatory responses as well as regulate tissue metabolism. Thus, they may provide a link between inflammation and other pathologic findings seen in equine joint disease. The aims of this thesis were to gain a deeper understanding of the development of chondral pathology in equine osteoarthritis (OA) by obtaining increased knowledge of inflammatory processes in the joint, and to investigate proinflammatory cytokines as markers of joint pathology. Measuremen...

  4. Transcompartmental Inflammatory Responses in Humans

    DEFF Research Database (Denmark)

    Plovsing, Ronni R; Berg, Ronan M G; Evans, Kevin A

    2014-01-01

    OBJECTIVES: Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following lipopolysacchar......OBJECTIVES: Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following......-α, interleukin-6, and albumin (all p humans is followed by a transcompartmental proinflammatory response, the degree and differential...

  5. Inflammatory Response in Islet Transplantation

    Directory of Open Access Journals (Sweden)

    Mazhar A. Kanak

    2014-01-01

    Full Text Available Islet cell transplantation is a promising beta cell replacement therapy for patients with brittle type 1 diabetes as well as refractory chronic pancreatitis. Despite the vast advancements made in this field, challenges still remain in achieving high frequency and long-term successful transplant outcomes. Here we review recent advances in understanding the role of inflammation in islet transplantation and development of strategies to prevent damage to islets from inflammation. The inflammatory response associated with islets has been recognized as the primary cause of early damage to islets and graft loss after transplantation. Details on cell signaling pathways in islets triggered by cytokines and harmful inflammatory events during pancreas procurement, pancreas preservation, islet isolation, and islet infusion are presented. Robust control of pre- and peritransplant islet inflammation could improve posttransplant islet survival and in turn enhance the benefits of islet cell transplantation for patients who are insulin dependent. We discuss several potent anti-inflammatory strategies that show promise for improving islet engraftment. Further understanding of molecular mechanisms involved in the inflammatory response will provide the basis for developing potent therapeutic strategies for enhancing the quality and success of islet transplantation.

  6. Editorial. Sustainability: A social responsability

    OpenAIRE

    Palmero Iglesias, Luis

    2017-01-01

    Editorial nº2_1 Palmero Iglesias, L. (2017). Editorial. Sustainability: A social responsability. VITRUVIO - International Journal of Architectural Technology and Sustainability. (1):vii-viii. doi:10.4995/vitruvio-ijats.2017.7650. vii viii 1 2

  7. Responsible marketing for sustainable tourism

    Directory of Open Access Journals (Sweden)

    Jegdić Vaso

    2014-01-01

    Full Text Available The biggest challenge associated with the concept of sustainable tourism is its operationalisation and perception as a process to be applied through development plans, projects and ongoing activities of tour operators. The traditional approach to marketing, focused on a limited idea of maximising profit businesses, was not able to respond to a number of social and environmental requirements imposed by the concept of sustainable development. This paper discusses the ways in which marketing could play a more important role in the sustainable development of tourism. This refers to the determination of consumer needs and preferences, the formation of certain products and pricing, product information and advertising to consumers of their benefits in a sustainable manner, as well as adequate distribution channels used by businesses to deliver products to consumers. Environmental and social marketing are now being confirmed as important elements of a much broader marketing perspective. In order to develop tourism with sustainable outcomes, responsible marketing can be crucial. The concept of marketing mix for sustainable tourism was used as a starting point to explore the specific role of responsible marketing in tourism.

  8. Corporate Social Responsibility for Sustainability

    Directory of Open Access Journals (Sweden)

    Wojciech Przychodzeń

    2014-06-01

    Full Text Available Purpose: The purpose of this paper is to is to provide insights on implementing corporate social responsibility for sustainability (CSRS concept and show how it differs from basic corporate social responsibility (CSR. Methodology: The paper discusses major issues with references to existing literature and real business cases from S&P500 consumer discretionary sector. Findings: The main fi nding of this paper is that CSRS could provide the company with a competitive advantage as a growing number of consumers become more sustainable conscious. It could also help to overcome the increasing consumers’ skepticism towards corporate social responsibility practices. Finally, it can also be seen as a step forward in defi ning what types of corporate activities are associated with desirable social and environmental gains. Research limitations: Our sample was restricted to the U.S. fi rms from the consumer discretionary sector. Therefore, conclusions should not be generalized to other markets. Our study is based on the analysis of environmental and social responsibility statements and assumes that they accurately represent corporate commitment in majority of the cases. Practical implications: CSRS offers corporations the opportunity to use their unique skills, culture, values, resources, and management capabilities to lead social progress by making sustainability part of its internal corporate logic. Originality: The paper raises the importance of the different conditions necessary for making sustainable development concept an important part of corporate strategy.

  9. Systemic inflammatory response following acute myocardial infarction

    National Research Council Canada - National Science Library

    Lu FANG Xiao-Lei Moorea Anthony M Dart Le-Min WANG

    2015-01-01

    Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns, activating complement and toll-like receptor/interleukin-1 signaling, and triggering an intense inflammatory response...

  10. Inflammatory Acute Response. Biochemical and Cellular Considerations

    National Research Council Canada - National Science Library

    Milagros Lisset León Regal; Ania Alvarado Borges; José Omar de Armas García; Luciano Miranda Alvarado; Javier Antonio Varens Cedeño; José Ángel Cuesta del Sol

    2015-01-01

    .... The present work aimed at argumenting on the mechanisms that explain the vascular changes, and the establishment of the signs of the acute inflammatory response with an in-depth molecular level...

  11. Systemic Inflammatory Response and Adhesion Molecules

    Directory of Open Access Journals (Sweden)

    L. V. Molchanova

    2005-01-01

    Full Text Available The lecture presents the materials of foreign studies on the mechanisms responsible for the formation of a systemic inflammatory response syndrome (SIRS. The hypotheses accounting for the occurrence of SIRS in emergencies are described. Adhesion molecules (AM and endothelial dysfunction are apparent to be involved in the inflammatory process, no matter what the causes of SIRS are. The current classification of AM and adhesion cascades with altered blood flow is presented. There are two lines in the studies of AM. One line is to measure the concentration of AM in the plasma of patients with emergencies of various etiology. The other is to study the impact of antiadhesion therapy on the alleviation of the severity of terminal state and its outcome. The studies provide evidence for that an adhesive process is a peculiar prelude to a systemic inflammatory response.

  12. Pronounced inflammatory response to endotoxaemia during nighttime

    DEFF Research Database (Denmark)

    Alamili, Mahdi; Bendtzen, Klaus; Lykkesfeldt, Jens

    2014-01-01

    -night difference in the acute phase response to endotoxaemia exists in healthy volunteers with a more pronounced inflammatory response during the night time. This circadian difference in the response to endotoxaemia may play an important role in the clinical setting and should be investigated further.......BACKGROUND: Circadian variation in bodily functions has been shown to impact health in acute and chronic medical conditions. Little is known about the relationship between circadian rhythm and sepsis in humans. We aimed to investigate circadian variations in the host response in a human...... endotoxaemia model. DESIGN AND METHODS: A cross-over study, where 12 healthy young men received E. coli endotoxin (lipopolysaccharide, LPS) 0.3 ng/kg at 12 noon and, on another day, at 12 midnight. Blood samples were analysed for pro- and anti-inflammatory cytokines: tumour-necrosis factor (TNF)-alpha, soluble...

  13. Sustained release of a p38 inhibitor from non-inflammatory microspheres inhibits cardiac dysfunction

    Science.gov (United States)

    Sy, Jay C.; Seshadri, Gokulakrishnan; Yang, Stephen C.; Brown, Milton; Oh, Teresa; Dikalov, Sergey; Murthy, Niren; Davis, Michael E.

    2008-11-01

    Cardiac dysfunction following acute myocardial infarction is a major cause of death in the world and there is a compelling need for new therapeutic strategies. In this report we demonstrate that a direct cardiac injection of drug-loaded microparticles, formulated from the polymer poly(cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK), improves cardiac function following myocardial infarction. Drug-delivery vehicles have great potential to improve the treatment of cardiac dysfunction by sustaining high concentrations of therapeutics within the damaged myocardium. PCADK is unique among currently used polymers in drug delivery in that its hydrolysis generates neutral degradation products. We show here that PCADK causes minimal tissue inflammatory response, thus enabling PCADK for the treatment of inflammatory diseases, such as cardiac dysfunction. PCADK holds great promise for treating myocardial infarction and other inflammatory diseases given its neutral, biocompatible degradation products and its ability to deliver a wide range of therapeutics.

  14. Natural Products: Insights into Leishmaniasis Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Igor A. Rodrigues

    2015-01-01

    Full Text Available Leishmaniasis is a vector-borne disease that affects several populations worldwide, against which there are no vaccines available and the chemotherapy is highly toxic. Depending on the species causing the infection, the disease is characterized by commitment of tissues, including the skin, mucous membranes, and internal organs. Despite the relevance of host inflammatory mediators on parasite burden control, Leishmania and host immune cells interaction may generate an exacerbated proinflammatory response that plays an important role in the development of leishmaniasis clinical manifestations. Plant-derived natural products have been recognized as bioactive agents with several properties, including anti-protozoal and anti-inflammatory activities. The present review focuses on the antileishmanial activity of plant-derived natural products that are able to modulate the inflammatory response in vitro and in vivo. The capability of crude extracts and some isolated substances in promoting an anti-inflammatory response during Leishmania infection may be used as part of an effective strategy to fight the disease.

  15. Partiality of Responsibility: Ethics in Sustainability Consulting

    NARCIS (Netherlands)

    Earhart, R.S.

    2011-01-01

    Sustainability, Socially Responsible Investment (SRI) and Corporate Social Responsibility (CSR) are both highly normative fields of professional practice, framed by various narratives: capitalist versus environmentalist, waste versus respect for the planet, consumerism versus responsibility;

  16. Interplay between Inflammatory Responses and Lymphatic Vessels.

    Science.gov (United States)

    Shin, Kihyuk; Lee, Seung-Hyo

    2014-08-01

    Lymphatic vessels are routes for leukocyte migration and fluid drainage. In addition to their passive roles in migration of leukocytes, increasing evidence indicates their active roles in immune regulation. Tissue inflammation rapidly induces lymphatic endothelial cell proliferation and chemokine production, thereby resulting in lymphangiogenesis. Furthermore, lymphatic endothelial cells induce T cell tolerance through various mechanisms. In this review, we focus on the current knowledge on how inflammatory cytokines affect lymphangiogenesis and the roles of lymphatic vessels in modulating immune responses.

  17. Inflammatory monocytes hinder antiviral B cell responses.

    Science.gov (United States)

    Sammicheli, Stefano; Kuka, Mirela; Di Lucia, Pietro; de Oya, Nereida Jimenez; De Giovanni, Marco; Fioravanti, Jessica; Cristofani, Claudia; Maganuco, Carmela G; Fallet, Benedict; Ganzer, Lucia; Sironi, Laura; Mainetti, Marta; Ostuni, Renato; Larimore, Kevin; Greenberg, Philip D; de la Torre, Juan Carlos; Guidotti, Luca G; Iannacone, Matteo

    2016-10-21

    Antibodies are critical for protection against viral infections. However, several viruses, such as lymphocytic choriomeningitis virus (LCMV), avoid the induction of early protective antibody responses by poorly understood mechanisms. Here we analyzed the spatiotemporal dynamics of B cell activation to show that, upon subcutaneous infection, LCMV-specific B cells readily relocate to the interfollicular and T cell areas of the draining lymph node where they extensively interact with CD11b(+)Ly6C(hi) inflammatory monocytes. These myeloid cells were recruited to lymph nodes draining LCMV infection sites in a type I interferon-, CCR2-dependent fashion and they suppressed antiviral B cell responses by virtue of their ability to produce nitric oxide. Depletion of inflammatory monocytes, inhibition of their lymph node recruitment or impairment of their nitric oxide-producing ability enhanced LCMV-specific B cell survival and led to robust neutralizing antibody production. In conclusion, our results identify inflammatory monocytes as critical gatekeepers that prevent antiviral B cell responses and suggest that certain viruses take advantage of these cells to prolong their persistence within the host.

  18. Neuroimmune regulation of inflammatory responses in inflammatory bowel disease

    NARCIS (Netherlands)

    Rijnierse, Anneke

    2006-01-01

    The term inflammatory bowel disease (IBD) is used to describe chronic inflammatory conditions of the gastro-intestinal tract. Patients suffer from abdominal pain, diarrhea, rectal bleeding and a substantial personal burden. The etiology of IBD is gradually being unraveled but remains a complex

  19. Auditory sustained field responses to periodic noise

    Directory of Open Access Journals (Sweden)

    Keceli Sumru

    2012-01-01

    Full Text Available Abstract Background Auditory sustained responses have been recently suggested to reflect neural processing of speech sounds in the auditory cortex. As periodic fluctuations below the pitch range are important for speech perception, it is necessary to investigate how low frequency periodic sounds are processed in the human auditory cortex. Auditory sustained responses have been shown to be sensitive to temporal regularity but the relationship between the amplitudes of auditory evoked sustained responses and the repetitive rates of auditory inputs remains elusive. As the temporal and spectral features of sounds enhance different components of sustained responses, previous studies with click trains and vowel stimuli presented diverging results. In order to investigate the effect of repetition rate on cortical responses, we analyzed the auditory sustained fields evoked by periodic and aperiodic noises using magnetoencephalography. Results Sustained fields were elicited by white noise and repeating frozen noise stimuli with repetition rates of 5-, 10-, 50-, 200- and 500 Hz. The sustained field amplitudes were significantly larger for all the periodic stimuli than for white noise. Although the sustained field amplitudes showed a rising and falling pattern within the repetition rate range, the response amplitudes to 5 Hz repetition rate were significantly larger than to 500 Hz. Conclusions The enhanced sustained field responses to periodic noises show that cortical sensitivity to periodic sounds is maintained for a wide range of repetition rates. Persistence of periodicity sensitivity below the pitch range suggests that in addition to processing the fundamental frequency of voice, sustained field generators can also resolve low frequency temporal modulations in speech envelope.

  20. Scorpion Venom and the Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Vera L. Petricevich

    2010-01-01

    Full Text Available Scorpion venoms consist of a complex of several toxins that exhibit a wide range of biological properties and actions, as well as chemical compositions, toxicity, and pharmacokinetic and pharmacodynamic characteristics. These venoms are associated with high morbility and mortality, especially among children. Victims of envenoming by a scorpion suffer a variety of pathologies, involving mainly both sympathetic and parasympathetic stimulation as well as central manifestations such as irritability, hyperthermia, vomiting, profuse salivation, tremor, and convulsion. The clinical signs and symptoms observed in humans and experimental animals are related with an excessive systemic host inflammatory response to stings and stings, respectively. Although the pathophysiology of envenomation is complex and not yet fully understood, venom and immune responses are known to trigger the release of inflammatory mediators that are largely mediated by cytokines. In models of severe systemic inflammation produced by injection of high doses of venom or venoms products, the increase in production of proinflammatory cytokines significantly contributes to immunological imbalance, multiple organ dysfunction and death. The cytokines initiate a cascade of events that lead to illness behaviors such as fever, anorexia, and also physiological events in the host such as activation of vasodilatation, hypotension, and increased of vessel permeability.

  1. Sex differences in the myocardial inflammatory response to acute injury

    National Research Council Canada - National Science Library

    Kher, Ajay; Wang, Meijing; Tsai, Ben M; Pitcher, Jeffrey M; Greenbaum, Evan S; Nagy, Ryan D; Patel, Ketan M; Wairiuko, G Mathenge; Markel, Troy A; Meldrum, Daniel R

    2005-01-01

    .... These insults lead to an inflammatory cascade, which plays an important role in this process. Gender has been shown to influence the inflammatory response, as well as outcomes after acute injury...

  2. Papanicolaou smears and cervical inflammatory cytokine responses

    Directory of Open Access Journals (Sweden)

    Shapiro Samual

    2007-04-01

    Full Text Available Abstract In a case-control study among 2064 South African women to investigate the risk of clinically invasive cancer of the cervix, we found a marked reduction in the risk of cervical cancer among women who gave a history of ever having undergone even a single Pap smear, and a statistically significant decline in the HPV positivity rate correlated with the lifetime number of Pap smears received. HPV infections and their associated low-grade lesions commonly regress, indicating that most often there is an effective host immune response against HPV infection. We hypothesized that act of performing a Pap smear is associated with inflammatory responses at the site of trauma, the cervix, and that this inflammatory signalling may be an immunological factor initiating these productive anti-HPV responses. In the present study, a randomized controlled trial, we enrolled 80 healthy young women to investigate the impact of performing a Pap smear on cervical inflammation. Forty one women, in the intervention group, received a Pap smear at enrollment and cervicovaginal lavages (CVLs were collected at baseline and 2 weeks later. Thirty nine women received no intervention at enrollment (control group but CVLs were collected at enrolment and 2 weeks later. We assessed various markers of inflammation including IL-12 p70, TNF-α, IL-8, IL-6, IL-10, and IL-1β in CVL specimens. While CVL levels of IL-8, IL-1β and IL-6 remained unchanged following a Pap smear, markers of cell mediated immunity (IL-12 p70 and TNF-α and T cell regulation (IL-10 were significantly elevated.

  3. Responsible and sustainable business in the context of sustainable development

    Directory of Open Access Journals (Sweden)

    Gheorghe Săvoiu

    2013-11-01

    Full Text Available Businesses in the contemporary world, detached from the classic entrepreneurial paradigm in keeping with which a business appears, grows and matures, are undergoing a process of adjustment to the new concept of sustainability, focusing on reconciling global, regional, national and local economic development and the quality of the environment. The practical organization of a responsible and sustainable business, the results of which are ever new products and services, which creates new jobs, and contributes, by aggregating systematically, to assessing new macroeconomic results, from GDP or NDP to import and export, and especially to sustainable economic development, requires the presence of both the three classical factors, i.e., capital, labour and location (land, and the other three essential new factors, which are called technology, information and the specific skills of the business owner, or simply of the entrepreneur.

  4. Ticagrelor induced systemic inflammatory response syndrome.

    Science.gov (United States)

    Krisai, Philipp; Haschke, Manuel; Buser, Peter T; Mueller, Christian

    2017-01-06

    Ticagrelor is a reversible and direct-acting oral antagonist of the adenosine diphosphate receptor P2Y12. Possible adenosine-mediated effects of ticagrelor on inflammation are complex and incompletely understood. To our knowledge, ticagrelor-induced systemic inflammatory response syndrome (SIRS) has not yet been described. We report the case of an 84 years old patient presenting with SIRS subsequent to initiation of ticagrelor after implantation of two drug eluting stents. A broad diagnostic work-up for alternative causes and therapeutic measures were unrevealing. Discontinuation of the agent was followed by rapid improvement in clinical and laboratory signs of SIRS. After exclusion of other causes, ticagrelor needs to be considered as a possible causative agent for SIRS. Due to the widespread use of ticagrelor, clinicians should be aware of this possible adverse drug reaction.

  5. Plasma inflammatory biomarkers response to aerobic versus ...

    African Journals Online (AJOL)

    kelsen etal. proved that life-long endurance exercise was associated with a lower level of the inflammatory mark- ers CRP and IL-6 in elderly subjects27. While, Sugawara etal. concluded that the levels of elevated inflammatory cytokines decreased significantly after intervention with an anti-inflammatory nutrition combined ...

  6. Corporate Social Responsibility and Sustainability in Scandinavia

    DEFF Research Database (Denmark)

    Strand, Robert; Freeman, R. Edward; Hockerts, Kai

    2015-01-01

    Scandinavia is routinely cited as a global leader in corporate social responsibility (CSR) and sustainability. In this article, we explore the foundation for this claim while also exploring potential contributing factors. We consider the deep-seated traditions of stakeholder engagement across...... this may entail. In sum, we depict the state of the art in CSR and sustainability in Scandinavia. We intend for this to serve as a basis to help establish a globally recognized research paradigm dedicated to considering CSR and sustainability in a Scandinavian context....

  7. Lipid droplets in Leukocytes: organelles linked to inflammatory responses

    OpenAIRE

    Melo, Rossana C. N.; Weller, Peter F.

    2015-01-01

    Studies on lipid droplets (LDs) in leukocytes have attracted attention due to their association with human diseases. In these cells, LDs are rapidly formed in response to inflammatory stimuli or allergic/inflammatory diseases including infections with parasites and bacteria. Leukocyte LDs are linked to the regulation of immune responses by compartmentalization of several proteins and lipids involved in the control and biosynthesis of inflammatory mediators (eicosanoids). In this mini review, ...

  8. Thrombin promotes sustained signaling and inflammatory gene expression through the CDC25 and Ras-associating domains of phospholipase Cϵ.

    Science.gov (United States)

    Dusaban, Stephanie S; Kunkel, Maya T; Smrcka, Alan V; Brown, Joan Heller

    2015-10-30

    Phospholipase C-epsilon (PLCϵ) plays a critical role in G-protein-coupled receptor-mediated inflammation. In addition to its ability to generate the second messengers inositol 1,4,5-trisphosphate and diacylglycerol, PLCϵ, unlike the other phospholipase C family members, is activated in a sustained manner. We hypothesized that the ability of PLCϵ to function as a guanine nucleotide exchange factor (GEF) for Rap1 supports sustained downstream signaling via feedback of Rap1 to the enzyme Ras-associating (RA2) domain. Using gene deletion and adenoviral rescue, we demonstrate that both the GEF (CDC25 homology domain) and RA2 domains of PLCϵ are required for long term protein kinase D (PKD) activation and subsequent induction of inflammatory genes. PLCϵ localization is largely intracellular and its compartmentalization could contribute to its sustained activation. Here we show that localization of PLCϵ to the Golgi is required for activation of PKD in this compartment as well as for subsequent induction of inflammatory genes. These data provide a molecular mechanism by which PLCϵ mediates sustained signaling and by which astrocytes mediate pathophysiological inflammatory responses. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Inflammatory Response to Cardiac Surgery and Strategies to Overcome it.

    Directory of Open Access Journals (Sweden)

    Kapoor Mukul

    2004-01-01

    Full Text Available A general activation of the immune system is observed during any operative procedure as a physiological response to the surgical trauma. Cardiopulmonary bypass may directly activate the inflammatory response by three distinct mechanisms: direct ′contact activation′ of the immune system following exposure of blood to the foreign surfaces, ischaemia-reperfusion injury to vital organs and systemic endotoxaemia resulting from gut translocation of endotoxin. The inflammatory response depends upon recruitment and activation of inflammatory cells. The cellular immune response, in particular polymorphonuclear cell-endothelial adhesion, leads to widespread endothelial damage and dysfunction. Increased oxygen derived free radical activity represents a risk for myocardial and pulmonary complications. The clinical consequences of the stress response vary from a mild generalised transient response, termed the ′systemic inflammatory response syndrome,′ to life threatening organ dysfunction. The introduction of the ′off-pump′ coronary artery bypass graft surgery has now made it possible to differentiate the influence of cardiopulmonary bypass and surgical access on different modalities of the immune response. ′Off-pump′ cardiac surgery has been found to trigger inflammatory response, lesser than ′on-pump′ cardiac surgery. Researches are directed towards understanding this complex interplay of humoral and cellular mediators and develop strategies to limit the resultant organ dysfunction. Current literature on the various mediators of this inflammatory response, the role of surgical stress, the pathogenesis of the organ damage and strategies to limit / overcome this response are reviewed.

  10. Sustainable Enterprise Excellence and the Continuously Relevant and Responsible Organization

    DEFF Research Database (Denmark)

    Edgeman, Rick; Bøllingtoft, Anne; Eskildsen, Jacob Kjær

    2013-01-01

    issues surrounding enterprise innovation and sustainability efforts and capabilities. Innovation and sustainability of the necessary trajectory, scale, and velocity are strategically integrated to deliver what we refer to as innovating sustainability. This provides an accelerated means path toward...... sustainable enterprise excellence, and hence toward the asymptotic aspiration of being a continuously relevant and responsible organization. Introduced are the concepts of innovating sustainability, sustainable enterprise excellence (SEE), and continuously relevant and responsible organizations (CRRO)....

  11. SUSTAINABLE DEVELOPMENT AND ECOLOGICAL RESPONSIBILITY OF BUSINESS

    Directory of Open Access Journals (Sweden)

    Viktoria Krykun

    2016-11-01

    Full Text Available Today sustainable development is a widely used term, which has been increasingly influential in recent years. Debates about sustainability no longer consider sustainability solely as an environmental concern, but also incorporate economic and social dimensions. However, while a social and economic dimensions of sustainable development are widely discussed, environmental degradation becomes more and more crucial each year and is likely to reduce human well-being all across the world within the next few decades. The purpose of the paper is to analyse ecological ‘pillar’ of sustainable development, its historical background, main steps towards implementation of ‘new global environmental rules for society. Methodology. The paper is based on statistical information from public sources, reports of different international organizations and institutions, which are used to stress and underline main crucial points of research. Results of the survey show, that environmental quality, economic development and social well-being are interdependent and the main aim of international institutions, independent countries, businesses and society is to achieve environmentally sustainable development. Environmental issues make strong impact on modern economy. Responsible global strategy of development provides the whole society with rules, how ‘wise’ technological changes and economic policy can make industrial production processes less polluting and less resource intensive but yet more productive and profitable. Practical implications. Strategy of sustainable development and it’s three basic dimensions have found practical implication in one complex model, which illustrates the level of development of each country – the Human Development Index, which is focusing on three basic dimensions of human development: life expectancy at birth, mean years of schooling and expected years of schooling and gross national income per capita. Another data, which is

  12. Systemic inflammatory responses following welding inhalation challenge test

    Directory of Open Access Journals (Sweden)

    Paula Kauppi

    2015-01-01

    Conclusions: Exposure to MS and SS welding fume resulted in a mild systemic inflammatory response. The particle concentration from the breathing zones correlated with the measurements inside the welding face shields.

  13. Macrophage Expression of Inflammatory Genes in Response to EMCV Infection

    Directory of Open Access Journals (Sweden)

    Zachary R. Shaheen

    2015-08-01

    Full Text Available The expression and production of type 1 interferon is the classic cellular response to virus infection. In addition to this antiviral response, virus infection also stimulates the production of proinflammatory mediators. In this review, the pathways controlling the induction of inflammatory genes and the roles that these inflammatory mediators contribute to host defense against viral pathogens will be discussed. Specific focus will be on the role of the chemokine receptor CCR5, as a signaling receptor controlling the activation of pathways leading to virus-induced inflammatory gene expression.

  14. Lipid droplets in leukocytes: Organelles linked to inflammatory responses.

    Science.gov (United States)

    Melo, Rossana C N; Weller, Peter F

    2016-01-15

    Studies on lipid droplets (LDs) in leukocytes have attracted attention due to their association with human diseases. In these cells, LDs are rapidly formed in response to inflammatory stimuli or allergic/inflammatory diseases including infections with parasites and bacteria. Leukocyte LDs are linked to the regulation of immune responses by compartmentalization of several proteins and lipids involved in the control and biosynthesis of inflammatory mediators (eicosanoids). In this mini review, we summarize current knowledge on the composition, structure and function of leukocyte LDs, organelles now considered as structural markers of inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Senescence-associated inflammatory responses: aging and cancer perspectives.

    Science.gov (United States)

    Lasry, Audrey; Ben-Neriah, Yinon

    2015-04-01

    Senescent cells, albeit not proliferating, are metabolically and transcriptionally active, thereby capable of affecting their microenvironment, notably via the production of inflammatory mediators. These mediators maintain and propagate the senescence process to neighboring cells, and then recruit immune cells for clearing senescent cells. Among the inflammatory cues are molecules with pronounced tumor-controlling properties, both growth and invasion factors and inhibitory factors, working directly or via recruited immune cells. These senescence-inflammatory effects also prevail within tumors, mediated by the senescent tumor cells and the senescent tumor stroma. Here, we review the course and impact of senescence-associated inflammatory responses in aging and cancer. We propose that controlling senescence-associated inflammation by targeting specific inflammatory mediators may have a beneficial therapeutic effect in treatment of cancer and aging-related diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Enhanced acute anti-inflammatory effects of CORM-2-loaded nanoparticles via sustained carbon monoxide delivery.

    Science.gov (United States)

    Qureshi, Omer Salman; Zeb, Alam; Akram, Muhammad; Kim, Myung-Sic; Kang, Jong-Ho; Kim, Hoo-Seong; Majid, Arshad; Han, Inbo; Chang, Sun-Young; Bae, Ok-Nam; Kim, Jin-Ki

    2016-11-01

    The aim of this study was to enhance the anti-inflammatory effects of carbon monoxide (CO) via sustained release of CO from carbon monoxide-releasing molecule-2-loaded lipid nanoparticles (CORM-2-NPs). CORM-2-NPs were prepared by hot high pressure homogenization method using trilaurin as a solid lipid core and Tween 20/Span 20/Myrj S40 as surfactant mixture. The physicochemical properties of CORM-2-NPs were characterized and CO release from CORM-2-NPs was assessed by myoglobin assay. In vitro anti-inflammatory effects were evaluated by nitric oxide assay in lipopolysaccharide-stimulated RAW 264.7 macrophages. In vivo anti-inflammatory activity was investigated by measuring paw volumes and histological examination in carrageenan-induced rat paw edema. Spherical CORM-2-NPs were around 100nm with narrow particle size distribution. The sustained CO release from CORM-2-NPs was observed and the half-life of CO release increased up to 10 times compared with CORM-2 solution. CORM-2-NPs showed enhanced in vitro anti-inflammatory effects by inhibition of nitric oxide production. Edema volume in rat paw was significantly reduced after treatment with CORM-2-NPs. Taken together, CORM-2-NPs have a great potential for CO therapeutics against inflammation via sustained release of CO. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Inflammatory response in periodontal tissue in children with Down syndrome

    OpenAIRE

    Tsilingaridis, Georgios

    2013-01-01

    Periodontal diseases are inflammatory diseases affecting the supporting tissues of the teeth. Subjects with Down syndrome have a higher prevalence of periodontal disease compared to healthy controls. Periodontal disease in Down syndrome is considered to be multifactorial, although the aetiology is uncertain. The aim of this thesis was to study the inflammatory response in periodontal tissue in terms of cytokines, prostaglandins, matrix metalloproteinases (MMPs) and tissue inhibitors of metall...

  18. The Acute Inflammatory Response in Trauma / Hemorrhage and ...

    African Journals Online (AJOL)

    Traumatic injury/hemorrhagic shock (T/HS) elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases including T/HS and traumatic brain injury (TBI). Inflammation is a ...

  19. Airways inflammatory and atopy-related responses in athletes ...

    African Journals Online (AJOL)

    Repeated hyperventilation of unconditioned air, as well as air containing irritants and/or allergens has been suggested to cause thermal, mechanical, or osmotic airway trauma resulting in damage to the airway epithelium. Subsequent airway inflammatory responses may be responsible for the development of atopy-related

  20. Inflammatory response to trauma: implications for coagulation and resuscitation.

    Science.gov (United States)

    Pierce, Albert; Pittet, Jean-François

    2014-04-01

    Recent studies have changed our understanding of the timing and interactions of the inflammatory processes and coagulation cascade following severe trauma. This review highlights this information and correlates its impact on the current clinical approach for fluid resuscitation and treatment of coagulopathy for trauma patients. Severe trauma is associated with a failure of multiple biologic emergency response systems that includes imbalanced inflammatory response, acute coagulopathy of trauma, and endovascular glycocalyx degradation with microcirculatory compromise. These abnormalities are all interlinked and related. Recent observations show that after severe trauma: proinflammatory and anti-inflammatory responses are concomitant, not sequential and resolution of the inflammatory response is an active process, not a passive one. Understanding these interrelated processes is considered extremely important for the development of future therapies for severe trauma in humans. Traumatic injuries continue to be a significant cause of mortality worldwide. Recent advances in understanding the mechanisms of end-organ failure, and modulation of the inflammatory response has important clinical implications regarding fluid resuscitation and treatment of coagulopathy.

  1. Inflammatory responses to influenza vaccination at the extremes of age.

    Science.gov (United States)

    McDonald, Jacqueline U; Zhong, Ziyun; Groves, Helen T; Tregoning, John S

    2017-08-01

    Age affects the immune response to vaccination, with individuals at the extremes of age responding poorly. The initial inflammatory response to antigenic materials shapes the subsequent adaptive response and so understanding is required about the effect of age on the profile of acute inflammatory mediators. In this study we measured the local and systemic inflammatory response after influenza vaccination or infection in neonatal, young adult and aged mice. Mice were immunized intramuscularly with inactivated influenza vaccine with and without the adjuvant MF59 and then challenged with H1N1 influenza. Age was the major factor affecting the inflammatory profile after vaccination: neonatal mice had more interleukin-1α (IL-1α), C-reactive protein (CRP) and granulocyte-macrophage colony-stimulating factor (GMCSF), young adults more tumour necrosis factor-α (TNF), and elderly mice more interleukin-1 receptor antagonist (IL-1RA), IL-2RA and interferon-γ-induced protein 10 (IP10). Notably the addition of MF59 induced IL-5, granulocyte colony-stimulating factor (G-CSF), Keratinocyte Chemotractant (KC) and monocyte chemoattractant protein 1 (MCP1) in all ages of animals and levels of these cytokines correlated with antibody responses. Age also had an impact on the efficacy of vaccination: neonatal and young adult mice were protected against challenge, but aged mice were not. There were striking differences in the localization of the cytokine response depending on the route of exposure: vaccination led to a high serum response whereas intranasal infection led to a low serum response but a high lung response. In conclusion, we demonstrate that age affects the inflammatory response to both influenza vaccination and infection. These age-induced differences need to be considered when developing vaccination strategies for different age groups. © 2017 John Wiley & Sons Ltd.

  2. Pathophysiology of the systemic inflammatory response after major accidental trauma

    DEFF Research Database (Denmark)

    Brøchner, Anne Craveiro; Toft, Palle

    2009-01-01

    ABSTRACT: BACKGROUND: Purpose of the present study was to describe the pathophysiology of the systemic inflammatory response after major trauma and the timing of final reconstructive surgery. Methods: An unsystematic review of the medical literature was performed and articles pertaining to the in......ABSTRACT: BACKGROUND: Purpose of the present study was to describe the pathophysiology of the systemic inflammatory response after major trauma and the timing of final reconstructive surgery. Methods: An unsystematic review of the medical literature was performed and articles pertaining...... to the inflammatory response to trauma were obtained. The literature selected was based on the preference and clinical expertise of authors. Discussion: The inflammatory response consists of hormonal metabolic and immunological components and the extent correlates with the magnitude of the tissue injury. After trauma...... and uncomplicated surgery a delicate balance between pro- and anti-inflammatory mediators is observed.Trauma patients are, however, often exposed, not only to the trauma, but to several evens in the form of initial surgery and later final reconstructive surgery. In this case immune paralysis associated...

  3. Hydrodynamic regulation of monocyte inflammatory response to an intracellular pathogen.

    Directory of Open Access Journals (Sweden)

    Shankar J Evani

    2011-01-01

    Full Text Available Systemic bacterial infections elicit inflammatory response that promotes acute or chronic complications such as sepsis, arthritis or atherosclerosis. Of interest, cells in circulation experience hydrodynamic shear forces, which have been shown to be a potent regulator of cellular function in the vasculature and play an important role in maintaining tissue homeostasis. In this study, we have examined the effect of shear forces due to blood flow in modulating the inflammatory response of cells to infection. Using an in vitro model, we analyzed the effects of physiological levels of shear stress on the inflammatory response of monocytes infected with chlamydia, an intracellular pathogen which causes bronchitis and is implicated in the development of atherosclerosis. We found that chlamydial infection alters the morphology of monocytes and trigger the release of pro-inflammatory cytokines TNF-α, IL-8, IL-1β and IL-6. We also found that the exposure of chlamydia-infected monocytes to short durations of arterial shear stress significantly enhances the secretion of cytokines in a time-dependent manner and the expression of surface adhesion molecule ICAM-1. As a functional consequence, infection and shear stress increased monocyte adhesion to endothelial cells under flow and in the activation and aggregation of platelets. Overall, our study demonstrates that shear stress enhances the inflammatory response of monocytes to infection, suggesting that mechanical forces may contribute to disease pathophysiology. These results provide a novel perspective on our understanding of systemic infection and inflammation.

  4. Resveratrol modulates innate and inflammatory responses in fish leucocytes.

    Science.gov (United States)

    Castro, R; Lamas, J; Morais, P; Sanmartín, M L; Orallo, F; Leiro, J

    2008-11-15

    Resveratrol (RESV; trans-3,5,4'-trihydroxystilbene), a phytoalexin that is produced by some plants, among other effects has well-known antioxidant, anti-inflammatory and immunomodulatory activities in mammals. In the present study, the effects of RESV on several functions of turbot, Psetta maxima (L.), kidney leucocytes (KLs) related to the innate and inflammatory responses were investigated. RESV exerted a dose-dependent inhibitory effect on the migratory response and on the production of reactive oxygen species in KL, after stimulation of the respiratory burst activity with phorbol myristate acetate (PMA). RESV also significantly inhibited the generation of the pro-inflammatory mediator prostaglandin E(2) (PGE(2)) in the supernatant of KL cultures stimulated with acidic sulphated polysaccharides (ASPs) from the seaweed Ulva rigida. The effects of the polyphenol on enzymatic activity and on myeloperoxidase (MPO) gene expression in neutrophils were also tested. It was found that RESV strongly inhibited intracellular and extracellular MPO activity, behaving as a noncompetitive and reversible inhibitor, and also induced a decrease in MPO mRNA levels in turbot neutrophils. These findings indicate that RESV exerts important modulatory effects on inflammatory responses in fish, and considering the importance of innate immunity in these vertebrates and the similarities with mammals, it may be possible to use fish for analysis of the effects of different substances on inflammatory responses.

  5. The immune response to Prevotella bacteria in chronic inflammatory disease

    DEFF Research Database (Denmark)

    Larsen, Jeppe Madura

    2017-01-01

    the hunt for disease-modulating bacteria. Emerging studies in humans have linked the increased abundance of Prevotella species at mucosal sites to localized and systemic disease, including periodontitis, bacterial vaginosis, rheumatoid arthritis, metabolic disorders and low-grade systemic inflammation......-8, IL-6 and CCL20, which can promote mucosal Th17 immune responses and neutrophil recruitment. Prevotella-mediated mucosal inflammation leads to systemic dissemination of inflammatory mediators, bacteria and bacterial products, which in turn may affect systemic disease outcomes. Studies in mice...... support a causal role of Prevotella as colonization experiments promote clinical and inflammatory features of human disease. When compared with strict commensal bacteria, Prevotella exhibit increased inflammatory properties, as demonstrated by augmented release of inflammatory mediators from immune cells...

  6. Sphingosine Kinases Are Not Required for Inflammatory Responses in Macrophages*

    Science.gov (United States)

    Xiong, Yuquan; Lee, Hyeuk Jong; Mariko, Boubacar; Lu, Yi-Chien; Dannenberg, Andrew J.; Haka, Abigail S.; Maxfield, Frederick R.; Camerer, Eric; Proia, Richard L.; Hla, Timothy

    2013-01-01

    Sphingosine kinases (Sphks), which catalyze the formation of sphingosine 1-phosphate (S1P) from sphingosine, have been implicated as essential intracellular messengers in inflammatory responses. Specifically, intracellular Sphk1-derived S1P was reported to be required for NFκB induction during inflammatory cytokine action. To examine the role of intracellular S1P in the inflammatory response of innate immune cells, we derived murine macrophages that lack both Sphk1 and Sphk2 (MΦ Sphk dKO). Compared with WT counterparts, MΦ Sphk dKO cells showed marked suppression of intracellular S1P levels whereas sphingosine and ceramide levels were strongly up-regulated. Cellular proliferation and apoptosis were similar in MΦ Sphk dKO cells compared with WT counterparts. Treatment of WT and MΦ Sphk dKO with inflammatory mediators TNFα or Escherichia coli LPS resulted in similar NFκB activation and cytokine expression. Furthermore, LPS-induced inflammatory responses, mortality, and thioglycolate-induced macrophage recruitment to the peritoneum were indistinguishable between MΦ Sphk dKO and littermate control mice. Interestingly, autophagic markers were constitutively induced in bone marrow-derived macrophages from Sphk dKO mice. Treatment with exogenous sphingosine further enhanced intracellular sphingolipid levels and autophagosomes. Inhibition of autophagy resulted in caspase-dependent cell death. Together, these data suggest that attenuation of Sphk activity, particularly Sphk2, leads to increased intracellular sphingolipids and autophagy in macrophages. PMID:24081141

  7. Genomic responses in mouse models poorly mimic human inflammatory diseases

    Science.gov (United States)

    Seok, Junhee; Warren, H. Shaw; Cuenca, Alex G.; Mindrinos, Michael N.; Baker, Henry V.; Xu, Weihong; Richards, Daniel R.; McDonald-Smith, Grace P.; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C.; López, Cecilia M.; Honari, Shari; Moore, Ernest E.; Minei, Joseph P.; Cuschieri, Joseph; Bankey, Paul E.; Johnson, Jeffrey L.; Sperry, Jason; Nathens, Avery B.; Billiar, Timothy R.; West, Michael A.; Jeschke, Marc G.; Klein, Matthew B.; Gamelli, Richard L.; Gibran, Nicole S.; Brownstein, Bernard H.; Miller-Graziano, Carol; Calvano, Steve E.; Mason, Philip H.; Cobb, J. Perren; Rahme, Laurence G.; Lowry, Stephen F.; Maier, Ronald V.; Moldawer, Lyle L.; Herndon, David N.; Davis, Ronald W.; Xiao, Wenzhong; Tompkins, Ronald G.; Abouhamze, Amer; Balis, Ulysses G. J.; Camp, David G.; De, Asit K.; Harbrecht, Brian G.; Hayden, Douglas L.; Kaushal, Amit; O’Keefe, Grant E.; Kotz, Kenneth T.; Qian, Weijun; Schoenfeld, David A.; Shapiro, Michael B.; Silver, Geoffrey M.; Smith, Richard D.; Storey, John D.; Tibshirani, Robert; Toner, Mehmet; Wilhelmy, Julie; Wispelwey, Bram; Wong, Wing H

    2013-01-01

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases. PMID:23401516

  8. Inflammatory response and cardioprotection during open-heart surgery: the importance of anaesthetics.

    Science.gov (United States)

    Suleiman, M-S; Zacharowski, K; Angelini, G D

    2008-01-01

    Open-heart surgery triggers an inflammatory response that is largely the result of surgical trauma, cardiopulmonary bypass, and organ reperfusion injury (e.g. heart). The heart sustains injury triggered by ischaemia and reperfusion and also as a result of the effects of systemic inflammatory mediators. In addition, the heart itself is a source of inflammatory mediators and reactive oxygen species that are likely to contribute to the impairment of cardiac pump function. Formulating strategies to protect the heart during open heart surgery by attenuating reperfusion injury and systemic inflammatory response is essential to reduce morbidity. Although many anaesthetic drugs have cardioprotective actions, the diversity of the proposed mechanisms for protection (e.g. attenuating Ca(2+) overload, anti-inflammatory and antioxidant effects, pre- and post-conditioning-like protection) may have contributed to the slow adoption of anaesthetics as cardioprotective agents during open heart surgery. Clinical trials have suggested at least some cardioprotective effects of volatile anaesthetics. Whether these benefits are relevant in terms of morbidity and mortality is unclear and needs further investigation. This review describes the main mediators of myocardial injury during open heart surgery, explores available evidence of anaesthetics induced cardioprotection and addresses the efforts made to translate bench work into clinical practice.

  9. Factors modulating the inflammatory response in acute gouty arthritis

    NARCIS (Netherlands)

    Cleophas, M.C.P.; Crisan, T.O.; Joosten, L.A.B.

    2017-01-01

    PURPOSE OF REVIEW: Gout is a common debilitating form of arthritis and despite our extensive knowledge on the pathogenesis its prevalence is still rising quickly. In the current review, we provide a concise overview of recent discoveries in factors tuning the inflammatory response to soluble uric

  10. Acute systemic inflammatory response after cardiac surgery in ...

    African Journals Online (AJOL)

    2017-09-03

    Sep 3, 2017 ... valve(s) replacement were enrolled, from a single center hospital, after informed consent was obtained. ... Cite as: Gojo MKE, Prakaschandra R. Acute systemic inflammatory response after cardiac surgery in patients infected with human im- ... on the HIV disease profile in correlation with alterations.

  11. Blockade of Glutamine Synthetase Enhances Inflammatory Response in Microglial Cells.

    Science.gov (United States)

    Palmieri, Erika M; Menga, Alessio; Lebrun, Aurore; Hooper, Douglas C; Butterfield, D Allan; Mazzone, Massimiliano; Castegna, Alessandra

    2017-03-10

    Microglial cells are brain-resident macrophages engaged in surveillance and maintained in a constant state of relative inactivity. However, their involvement in autoimmune diseases indicates that in pathological conditions microglia gain an inflammatory phenotype. The mechanisms underlying this change in the microglial phenotype are still unclear. Since metabolism is an important modulator of immune cell function, we focused our attention on glutamine synthetase (GS), a modulator of the response to lipopolysaccharide (LPS) activation in other cell types, which is expressed by microglia. GS inhibition enhances release of inflammatory mediators of LPS-activated microglia in vitro, leading to perturbation of the redox balance and decreased viability of cocultured neurons. GS inhibition also decreases insulin-mediated glucose uptake in microglia. In vivo, microglia-specific GS ablation enhances expression of inflammatory markers upon LPS treatment. In the spinal cords from experimental autoimmune encephalomyelitis (EAE), GS expression levels and glutamine/glutamate ratios are reduced. Recently, metabolism has been highlighted as mediator of immune cell function through the discovery of mechanisms that (behind these metabolic changes) modulate the inflammatory response. The present study shows for the first time a metabolic mechanism mediating microglial response to a proinflammatory stimulus, pointing to GS activity as a master modulator of immune cell function and thus unraveling a potential therapeutic target. Our study highlights a new role of GS in modulating immune response in microglia, providing insights into the pathogenic mechanisms associated with inflammation and new strategies of therapeutic intervention. Antioxid. Redox Signal. 26, 351-363.

  12. Social responsibility and corporate sustainability factors in Mexico

    National Research Council Canada - National Science Library

    Fernando Lámbarry

    2016-01-01

    .... However, corporate responsibility and sustainability are increasingly common among businessmen, so that literature has emerged on various approaches to this type of case identifying the factors...

  13. NGF and Its Receptors in the Regulation of Inflammatory Response

    Science.gov (United States)

    Minnone, Gaetana; De Benedetti, Fabrizio; Bracci-Laudiero, Luisa

    2017-01-01

    There is growing interest in the complex relationship between the nervous and immune systems and how its alteration can affect homeostasis and result in the development of inflammatory diseases. A key mediator in cross-talk between the two systems is nerve growth factor (NGF), which can influence both neuronal cell function and immune cell activity. The up-regulation of NGF described in inflamed tissues of many diseases can regulate innervation and neuronal activity of peripheral neurons, inducing the release of immune-active neuropeptides and neurotransmitters, but can also directly influence innate and adaptive immune responses. Expression of the NGF receptors tropomyosin receptor kinase A (TrkA) and p75 neurotrophin receptor (p75NTR) is dynamically regulated in immune cells, suggesting a varying requirement for NGF depending on their state of differentiation and functional activity. NGF has a variety of effects that can be either pro-inflammatory or anti-inflammatory. This apparent contradiction can be explained by considering NGF as part of an endogenous mechanism that, while activating immune responses, also activates pathways necessary to dampen the inflammatory response and limit tissue damage. Decreases in TrkA expression, such as that recently demonstrated in immune cells of arthritis patients, might prevent the activation by NGF of regulatory feed-back mechanisms, thus contributing to the development and maintenance of chronic inflammation. PMID:28492466

  14. Mitochondrial respiration controls lysosomal function during inflammatory T cell responses

    Science.gov (United States)

    Baixauli, Francesc; Acín-Pérez, Rebeca; Villarroya-Beltrí, Carolina; Mazzeo, Carla; Nuñez-Andrade, Norman; Gabandé-Rodriguez, Enrique; Dolores Ledesma, Maria; Blázquez, Alberto; Martin, Miguel Angel; Falcón-Pérez, Juan Manuel; Redondo, Juan Miguel; Enríquez, Jose Antonio; Mittelbrunn, Maria

    2016-01-01

    Summary The endolysosomal system is critical for the maintenance of cellular homeostasis. However, how endolysosomal compartment is regulated by mitochondrial function is largely unknown. We have generated a mouse model with defective mitochondrial function in CD4+ T lymphocytes by genetic deletion of the mitochondrial transcription factor A (Tfam). Mitochondrial respiration-deficiency impairs lysosome function, promotes p62 and sphingomyelin accumulation and disrupts endolysosomal trafficking pathways and autophagy, thus linking a primary mitochondrial dysfunction to a lysosomal storage disorder. The impaired lysosome function in Tfam-deficient cells subverts T cell differentiation toward pro-inflammatory subsets and exacerbates the in vivo inflammatory response. Restoration of NAD+ levels improves lysosome function and corrects the inflammatory defects in Tfam-deficient T cells. Our results uncover a mechanism by which mitochondria regulate lysosome function to preserve T cell differentiation and effector functions, and identify novel strategies for intervention in mitochondrial-related diseases. PMID:26299452

  15. Modulation of Hemostatic and Inflammatory Responses by Leptospira Spp.

    Directory of Open Access Journals (Sweden)

    Mônica L Vieira

    2016-05-01

    Full Text Available Leptospirosis is a worldwide spread zoonotic and neglected infectious disease of human and veterinary concern that is caused by pathogenic Leptospira species. In severe infections, hemostatic impairments such as coagulation/fibrinolysis dysfunction are frequently observed. These complications often occur when the host response is controlled and/or modulated by the bacterial pathogen. In the present investigation, we aimed to analyze the modulation of the hemostatic and inflammatory host responses by the bacterial pathogen Leptospira. The effects of leptospires and their secreted products on stimulation of human intrinsic and extrinsic pathways of coagulation were investigated by means of altered clotting times, assembly and activation of contact system and induction of tissue factor. We show that both extrinsic and intrinsic coagulation cascades are modulated in response to Leptospira or leptospiral secreted proteins. We further find that the pro-inflammatory mediator bradykinin is released following contact activation at the bacterial surface and that pro-coagulant microvesicles are shed from monocytes in response to infection. Also, we show that human leptospirosis patients present higher levels of circulating pro-coagulant microvesicles than healthy individuals. Here we show that both pathways of the coagulation system are modulated by leptospires, possibly leading to altered hemostatic and inflammatory responses during the disease. Our results contribute to the understanding of the leptospirosis pathophysiological mechanisms and may open new routes for the discovery of novel treatments for the severe manifestations of the disease.

  16. Modulation of Hemostatic and Inflammatory Responses by Leptospira Spp.

    Science.gov (United States)

    Vieira, Mônica L; Naudin, Clément; Mörgelin, Matthias; Romero, Eliete C; Nascimento, Ana Lucia T O; Herwald, Heiko

    2016-05-01

    Leptospirosis is a worldwide spread zoonotic and neglected infectious disease of human and veterinary concern that is caused by pathogenic Leptospira species. In severe infections, hemostatic impairments such as coagulation/fibrinolysis dysfunction are frequently observed. These complications often occur when the host response is controlled and/or modulated by the bacterial pathogen. In the present investigation, we aimed to analyze the modulation of the hemostatic and inflammatory host responses by the bacterial pathogen Leptospira. The effects of leptospires and their secreted products on stimulation of human intrinsic and extrinsic pathways of coagulation were investigated by means of altered clotting times, assembly and activation of contact system and induction of tissue factor. We show that both extrinsic and intrinsic coagulation cascades are modulated in response to Leptospira or leptospiral secreted proteins. We further find that the pro-inflammatory mediator bradykinin is released following contact activation at the bacterial surface and that pro-coagulant microvesicles are shed from monocytes in response to infection. Also, we show that human leptospirosis patients present higher levels of circulating pro-coagulant microvesicles than healthy individuals. Here we show that both pathways of the coagulation system are modulated by leptospires, possibly leading to altered hemostatic and inflammatory responses during the disease. Our results contribute to the understanding of the leptospirosis pathophysiological mechanisms and may open new routes for the discovery of novel treatments for the severe manifestations of the disease.

  17. Hospitableness and sustainable development: New responsibilities ...

    African Journals Online (AJOL)

    [CC BY 4.0] (http://creativecommons.org/licenses/by/4.0). Introduction. Within the hospitality industry, as in other industries, attention is given to environmental sustainability. Unfortunately, however, most hospitality companies are lagging behind in the process of becoming more sustainable (van Rheede & Blomme, 2012a).

  18. Effect of silica particle size on macrophage inflammatory responses.

    Directory of Open Access Journals (Sweden)

    Toshimasa Kusaka

    Full Text Available Amorphous silica particles, such as nanoparticles (<100 nm diameter particles, are used in a wide variety of products, including pharmaceuticals, paints, cosmetics, and food. Nevertheless, the immunotoxicity of these particles and the relationship between silica particle size and pro-inflammatory activity are not fully understood. In this study, we addressed the relationship between the size of amorphous silica (particle dose, diameter, number, and surface area and the inflammatory activity (macrophage phagocytosis, inflammasome activation, IL-1β secretion, cell death and lung inflammation. Irrespective of diameter size, silica particles were efficiently internalized by mouse bone marrow-derived macrophages via an actin cytoskeleton-dependent pathway, and induced caspase-1, but not caspase-11, activation. Of note, 30 nm-1000 nm diameter silica particles induced lysosomal destabilization, cell death, and IL-1β secretion at markedly higher levels than did 3000 nm-10000 nm silica particles. Consistent with in vitro results, intra-tracheal administration of 30 nm silica particles into mice caused more severe lung inflammation than that of 3000 nm silica particles, as assessed by measurement of pro-inflammatory cytokines and neutrophil infiltration in bronchoalveolar lavage fluid of mice, and by the micro-computed tomography analysis. Taken together, these results suggest that silica particle size impacts immune responses, with submicron amorphous silica particles inducing higher inflammatory responses than silica particles over 1000 nm in size, which is ascribed not only to their ability to induce caspase-1 activation but also to their cytotoxicity.

  19. Systemic inflammatory response syndrome: a case of septic shock

    Directory of Open Access Journals (Sweden)

    Nicolò Gentiloni Silveri

    2008-09-01

    Full Text Available An elderly, diabetic male, with severe sepsis, swiftly treated with antibiotics that were efficacious in vitro against the E. Coli isolated in his blood, rapidly slides into multiple organ dysfunction syndrome and dies of septic shock after a month in intensive care, despite receiving appropriate pain relief and aetiopathogenetic therapy. This event provides us with the opportunity to take a new look at systemic inflammatory response syndrome and a critical review of the relative therapy

  20. Practices of corporate social responsibility and sustainable systems work in Peruvian companies issuing sustainability reports

    Directory of Open Access Journals (Sweden)

    María Angela Prialé

    2015-12-01

    Full Text Available Through a literature review, this exploratory study seeks to determine whether the practices related to its colaborators, who report as part of its action responsible Peruvian companies issuing sustainability reports can be considered sustainable management practices of human resources. To this end, it was used the approach of sustainable work systems as a general approach. It was found that some of the practices of responsible management of human resources that implement the analyzed companies address the human dimensions of sustainability, although not all dimensions are considered equally or similar depth.

  1. Responsible Purchasing Network - Sustainable Purchasing Guidance Profile

    Science.gov (United States)

    To help you find the resource that is right for your organization, EPA conducted a scan of the landscape and developed summary profiles of some of the leading sources of sustainable purchasing guidance around the globe.

  2. Education as a response to sustainability issues

    Directory of Open Access Journals (Sweden)

    Katrien Van Poeck

    2014-05-01

    Full Text Available In the field of environmental education and education for sustainable development, there is a lively discussion about the paradox between acknowledging pluralism and taking into account urgent sustainability concerns. With this article, we aim at nurturing this debate theoretically and empirically. We draw on concepts of Latour and Marres that allow an analysis of educational practices that strive to take into account a multiplicity of views, values, interests and knowledge claims without resorting to an ‘anything goes’ relativism vis-à-vis the far-reaching implications of sustainability issues. We present an analysis of a guided tour of a CSA farm (Community Supported Agriculture and articulate how the care for a sustainability issue can incite an interesting educational dynamic (understood as ‘education as a respons’e that emerges as a derivative of ‘mastery’.

  3. Immunomodulation of the allergic inflammatory response: new developments.

    Science.gov (United States)

    Araujo, Maria I; Campos, Regis A; Cardoso, Luciana S; Oliveira, Sergio C; Carvalho, Edgar M

    2010-06-01

    Studies of the molecular mechanisms associated with allergic diseases have lead to a better understanding of the complex processes that underlie their pathogenesis. These mechanisms involve Th2- and Th1-type cells and also some recently described cytokines, such as IL-25 and IL-33. Regulatory mechanisms of allergic inflammation have also been identified. For instance, IL-10, a cytokine produced by many cell types, promotes a decrease in IgE production, and inhibits the release of histamine and other inflammatory mediators by mast cells. Recently, a variety of regulatory cells have been discovered, which, either by direct contact or through the production of IL-10 and/or TGF-beta, can inhibit the allergic inflammatory response. IL-10 is produced in high levels by cells of helminth-infected individuals. There is some evidence that such infections protect against the development of allergic diseases. In asthmatic individuals living in endemic areas of schistosomiasis, it has been shown in in vitro studies that there is a modulation of the Th2 response, both by mechanisms involving IL-10, which is produced mainly by monocytes and CD4+CD25+ T regulatory cells, and also by the expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) in CD4+ T cells. Studies using parasite antigens to induce the modulation of allergic inflammatory response are being conducted by several groups of researchers and represent new perspectives for the treatment of allergic diseases.

  4. The immune response to Prevotella bacteria in chronic inflammatory disease.

    Science.gov (United States)

    Larsen, Jeppe Madura

    2017-08-01

    The microbiota plays a central role in human health and disease by shaping immune development, immune responses and metabolism, and by protecting from invading pathogens. Technical advances that allow comprehensive characterization of microbial communities by genetic sequencing have sparked the hunt for disease-modulating bacteria. Emerging studies in humans have linked the increased abundance of Prevotella species at mucosal sites to localized and systemic disease, including periodontitis, bacterial vaginosis, rheumatoid arthritis, metabolic disorders and low-grade systemic inflammation. Intriguingly, Prevotella abundance is reduced within the lung microbiota of patients with asthma and chronic obstructive pulmonary disease. Increased Prevotella abundance is associated with augmented T helper type 17 (Th17) -mediated mucosal inflammation, which is in line with the marked capacity of Prevotella in driving Th17 immune responses in vitro. Studies indicate that Prevotella predominantly activate Toll-like receptor 2, leading to production of Th17-polarizing cytokines by antigen-presenting cells, including interleukin-23 (IL-23) and IL-1. Furthermore, Prevotella stimulate epithelial cells to produce IL-8, IL-6 and CCL20, which can promote mucosal Th17 immune responses and neutrophil recruitment. Prevotella-mediated mucosal inflammation leads to systemic dissemination of inflammatory mediators, bacteria and bacterial products, which in turn may affect systemic disease outcomes. Studies in mice support a causal role of Prevotella as colonization experiments promote clinical and inflammatory features of human disease. When compared with strict commensal bacteria, Prevotella exhibit increased inflammatory properties, as demonstrated by augmented release of inflammatory mediators from immune cells and various stromal cells. These findings indicate that some Prevotella strains may be clinically important pathobionts that can participate in human disease by promoting chronic

  5. Systemic inflammatory responses during laparoscopic and open inguinal hernia repair: a randomised prospective study

    DEFF Research Database (Denmark)

    Jess, P; Schultz, Karen; Bendtzen, K

    2000-01-01

    To see if the inflammatory responses during and after laparoscopic and open inguinal hernia repairs differed.......To see if the inflammatory responses during and after laparoscopic and open inguinal hernia repairs differed....

  6. Consumer Sustainability and Responsibility: Beyond Green and Ethical Consumption

    Directory of Open Access Journals (Sweden)

    Maja Hosta

    2016-12-01

    Full Text Available Purpose – Most literature regarding sustainable behavior is based on the assumption that the reduction of consumption is inherently positive (mainly in the form of positive environmental consequences and based on ethical considerations. However, the issue of the social consequences of this reduction and self-interested intentions in consumption is not generally open to debate. This paper aims to identify dimensions of sustainable and responsible consumer behavior, distinguish between the two concepts, and present consumer obstacles to acting responsibly in all aspects that a sustainability agenda would suggest. Design/Methodology/Approach – The paper includes a literature review, proposes a framework of responsible and sustainable consumption (RSCB, and offers a set of propositions to achieve responsible and sustainable consumption. Insights from personal interviews with consumers are added for the sake of additional understanding of the concepts presented. Findings and implications – Through the RSCB framework, we show the potential trade-off decisions consumers have to make in order to implement sustainability and responsibility issues in everyday consumer decision processes. Struggles between doing what is good for them and what is good for the environment and society could be a reason why consumers have difficulties achieving responsible and sustainable consumption. Limitations – Qualitative study based on a small sample of personal interviews does not allow for generalizations. Originality – A research gap in understanding the dimensions of sustainable and responsible consumer actions in terms of their emphasis (environmental and social and intentions (self-interest and other-interest is addressed. By understanding those two dimensions of behavior, managers and consumers can resolve consumer sustainability and responsibility dilemmas that arise from a one-dimensional view in order to move sustainability research and practice

  7. Sustainable Logistics Responses to a Global Challenge

    CERN Document Server

    Bretzke, Wolf-Rüdiger

    2013-01-01

    Currently the notion of "sustainability" is used in an inflationary manner. Therefore the authors start with a definition which is stable to serve as an anchor for further research as well as for discussions among scientists, managers and politicians, ideally across different disciplines. The character of this book is purely conceptual. The argumentation is based on comparison of new and demanding requisites with existing models (process and network architectures in the field of logistics). Formerly neglected impacts on the environment will be included. Main features of a new approach will be developed which are capable to avoid these impacts and to align logistics with the requirements of sustainability. In order to make logistics sustainable large parts will have to be reinvented. The focus needs to be on decoupling transportation activities from economic growth rates.

  8. Hospitableness and sustainable development: New responsibilities ...

    African Journals Online (AJOL)

    How does the current paradigm of the host-guest relationship cause the hospitality industry to lag behind in sustainable development? Hospitality is often defined as “a feeling of being welcome”. It is about “welcoming the stranger: a person who comes today and stays tomorrow”, or “a stranger who is treated like a god”.

  9. Inflammatory response after session of resistance exercises in untrained volunteers

    Directory of Open Access Journals (Sweden)

    Andre de Oliveira Teixeira

    2015-06-01

    Full Text Available The present study aimed to investigate the interaction between the blood cells, inflammatory markers, oxidative stress parameters and delayed onset muscle soreness (DOMS after a session of resistance exercise (SRE. The sample consisted of sixteen untrained men (26.4±5 years; 25.9±3 kg m-2. The SRE was composed of 4 sets of 10 repetitions maximum (extensor bench, squat and leg press for each exercise. Complete blood cell count, C-reactive protein (CRP, creatine kinase (CK, lipid peroxidation and antioxidant capacity against peroxyl radicals were previously evaluated (baseline, and at 0, 30 and 120 min. after the SRE. DOMS was assessed 24 hours after the exercises. Immediately after the SRE, an increase of blood cell number was observed; returning to baseline after 30 min. However, after 120 min., neutrophils showed higher values than the baseline and 30 min. assessments. CK and CRP increased progressively throughout the experiment. LPO increased immediately and 120 min. after the SRE. Untrained volunteers presented an apparent biphasic inflammatory response after an acute SRE and the changes in oxidative stress, inflammatory markers and leukocytosis were best evidenced two hours after exercise.

  10. Non inflammatory boronate based glucose-responsive insulin delivery systems.

    Directory of Open Access Journals (Sweden)

    Indrani Dasgupta

    Full Text Available Boronic acids, known to bind diols, were screened to identify non-inflammatory cross-linkers for the preparation of glucose sensitive and insulin releasing agglomerates of liposomes (Agglomerated Vesicle Technology-AVT. This was done in order to select a suitable replacement for the previously used cross-linker, ConcanavalinA (ConA, a lectin known to have both toxic and inflammatory effects in vivo. Lead-compounds were selected from screens that involved testing for inflammatory potential, cytotoxicity and glucose-binding. These were then conjugated to insulin-encapsulating nanoparticles and agglomerated via sugar-boronate ester linkages to form AVTs. In vitro, the particles demonstrated triggered release of insulin upon exposure to physiologically relevant concentrations of glucose (10 mmoles/L-40 mmoles/L. The agglomerates were also shown to be responsive to multiple spikes in glucose levels over several hours, releasing insulin at a rate defined by the concentration of the glucose trigger.

  11. Metabolic factors affecting the inflammatory response of periparturient dairy cows.

    Science.gov (United States)

    Sordillo, Lorraine M; Contreras, G A; Aitken, Stacey L

    2009-06-01

    Dairy cattle are susceptible to increased incidence and severity of disease during the periparturient period. Increased health disorders have been associated with alterations in bovine immune mechanisms. Many different aspects of the bovine immune system change during the periparturient period, but uncontrolled inflammation is a dominant factor in several economically important disorders such as metritis and mastitis. In human medicine, the metabolic syndrome is known to trigger several key events that can initiate and promote uncontrolled systemic inflammation. Altered lipid metabolism, increased circulating concentrations of non-esterified fatty acids and oxidative stress are significant contributing factors to systemic inflammation and the development of inflammatory-based diseases in humans. Dairy cows undergo similar metabolic adaptations during the onset of lactation, and it was postulated that some of these physiological events may negatively impact the magnitude and duration of inflammation. This review will discuss how certain types of fatty acids may promote uncontrolled inflammation either directly or through metabolism into potent lipid mediators. The relationship of increased lipid metabolism and oxidative stress to inflammatory dysfunction will be reviewed as well. Understanding more about the underlying cause of periparturient health disorders may facilitate the design of nutritional regimens that will meet the energy requirements of cows during early lactation and reduce the susceptibility to disease as a function of compromised inflammatory responses.

  12. Incidence of systemic inflammatory response syndrome after endovascular aortic repair

    DEFF Research Database (Denmark)

    De La Motte, L; Vogt, K; Jensen, Leif Panduro

    2011-01-01

    AIM: The aim of this study was to estimate the incidence of the post-implantation syndrome/systemic inflammatory response syndrome (SIRS) after endovascular aortic repair. METHODS: All patients, undergoing elective primary endovascular repair of an asymptomatic infrarenal abdominal aortic aneurysm...... of the contrast media used, type of groin access, adjunctive procedures and duration of surgery. In total, 11 (28%) patients in the SIRS group and 4 (15%) patients in the non-SIRS group underwent re-interventions. Median follow-up period was 26 (range 20-32) months. Thirty-day mortality did not differ...... in the groups (3% in the SIRS group vs. none in the non-SIRS group). CONCLUSION: The high incidence of SIRS after EVAR is unexpected considering the minimally invasive procedure. Further studies on the cause of this response and measures to attenuate the response seem appropriate....

  13. Inflammatory responses of stromal fibroblasts to inflammatory epithelial cells are involved in the pathogenesis of bovine mastitis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wenyao; Li, Xuezhong; Xu, Tong; Ma, Mengru [College of Veterinary Medicine, Northwest A& F University, Yangling 712100, Shaanxi (China); Zhang, Yong, E-mail: zhangyong1956@nwsuaf.edu.cn [College of Veterinary Medicine, Northwest A& F University, Yangling 712100, Shaanxi (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100, Shaanxi (China); Gao, Ming-Qing, E-mail: gaomingqing@nwsuaf.edu.cn [College of Veterinary Medicine, Northwest A& F University, Yangling 712100, Shaanxi (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100, Shaanxi (China)

    2016-11-15

    Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferation and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis. - Highlights: • Inflammatory BMEs affect the properties of BMFs during mastitis. • BMEs inhibited the proliferation and promoted the migration of BMFs. • BMEs enhanced secretion of inflammatory mediators and deposition of ECM in BMFs. • Changes of the properties of BMFs were mediated by specific signal molecules.

  14. Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity.

    Science.gov (United States)

    Sung, Nak Yoon; Kim, Mi-Yeon; Cho, Jae Youl

    2015-09-01

    Flavonoids are plant pigments that have been demonstrated to exert various pharmacological effects including anti-cancer, anti-diabetic, anti-atherosclerotic, anti-bacterial, and anti-inflammatory activities. However, the molecular mechanisms in terms of exact target proteins of flavonoids are not fully elucidated yet. In this study, we aimed to evaluate the anti-inflammatory mechanism of scutellarein (SCT), a flavonoid isolated from Erigeron breviscapus, Clerodendrum phlomidis and Oroxylum indicum Vent that have been traditionally used to treat various inflammatory diseases in China and Brazil. For this purpose, a nitric oxide (NO) assay, polymerase chain reaction (PCR), nuclear fractionation, immunoblot analysis, a kinase assay, and an overexpression strategy were employed. Scutellarein significantly inhibited NO production in a dose-dependent manner and reduced the mRNA expression levels of inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-activated RAW264.7 cells. In addition, SCT also dampened nuclear factor (NF)-κB-driven expression of a luciferase reporter gene upon transfection of a TIR-domain-containing adapter-inducing interferon-β (TRIF) construct into Human embryonic kidney 293 (HEK 293) cells; similarly, NF-κ B nuclear translocation was inhibited by SCT. Moreover, the phosphorylation levels of various upstream signaling enzymes involved in NF-κB activation were decreased by SCT treatment in LPS-treated RAW264.7 cells. Finally, SCT strongly inhibited Src kinase activity and also inhibited the autophosphorylation of overexpressed Src. Therefore, our data suggest that SCT can block the inflammatory response by directly inhibiting Src kinase activity linked to NF-κB activation.

  15. Assembly of a Tripeptide and Anti-Inflammatory Drugs into Supramolecular Hydrogels for Sustained Release

    Directory of Open Access Journals (Sweden)

    Marina Kurbasic

    2017-08-01

    Full Text Available Supramolecular hydrogels offer interesting opportunities for co-assembly with drugs towards sustained release over time, which could be achieved given that the drug participates in the hydrogel nanostructure, and it is not simply physically entrapped within the gel matrix. dLeu-Phe-Phe is an attractive building block of biomaterials in light of the peptide’s inherent biocompatibility and biodegradability. This study evaluates the assembly of the tripeptide in the presence of either of the anti-inflammatory drugs ketoprofen or naproxen at levels analogous to commercial gel formulations. Fourier-transformed infrared (FT-IR, circular dichroism, Thioflavin T fluorescence, transmission electron microscopy (TEM, and oscillatory rheometry are used. Drug release over time is monitored by means of reverse-phase high performance liquid chromatography, and shows different kinetics for the two drugs.

  16. Sustainable Development and Corporate Social Responsibility: Linking Goals to Standards

    Directory of Open Access Journals (Sweden)

    Radostina Bakardjieva

    2016-12-01

    Full Text Available Corporate social responsibility (CSR is the core of sustainable development of companies. On one hand, the corporate social responsibility of companies is a prerequisite for sustainable business, on the other - sustainable development sets specific requirements for the development of businesses in the context of increasing requirements to the degree of quality and reliability of financial information. In recent years, sustainable development has become a strategic issue for companies and this trend applies to Bulgarian companies too. Development of non-financial reporting is a very dynamic process, whose peak is the establishment of an integrated system of accountability. Current paper makes analyses of advantages of CSR linking it to the implementation of sustainable development goals through the integrated reporting following the requirements of the standards of the Global Reporting Initiative (GRI.

  17. Inflammatory responses to induced infectious endometritis in mares resistant or susceptible to persistent endometritis

    Directory of Open Access Journals (Sweden)

    Christoffersen Mette

    2012-03-01

    Full Text Available Abstract Background The objective of the study was to evaluate the gene expression of inflammatory cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-10, tumor necrosis factor [TNF]-α, IL-1 receptor antagonist [ra] and serum amyloid A (SAA in endometrial tissue and circulating leukocytes in response to uterine inoculation of 105 colony forming units (CFU Escherichia coli in mares. Before inoculation, mares were classified as resistant or susceptible to persistent endometritis based on their uterine inflammatory response to infusion of 109 killed spermatozoa and histological assessment of the endometrial quality. Endometrial biopsies were obtained 3, 12, 24 and 72 hours (h after bacterial inoculation and blood samples were obtained during the 7 day period post bacterial inoculation. Expression levels of cytokines and SAA were determined by quantitative real-time reverse transcriptase PCR (qRT-PCR. Results Compared to levels in a control biopsy (obtained in the subsequent estrous, resistant mares showed an up-regulation of IL-1β, IL-6, IL-8 and TNF-α at 3 h after E. coli inoculation, while susceptible mares showed increased gene expression of IL-6 and IL-1ra. Susceptible mares had a significant lower gene expression of TNF-α,IL-6 and increased expression of IL-1ra 3 h after E. coli inoculation compared to resistant mares. Susceptible mares showed a sustained and prolonged inflammatory response with increased gene expression levels of IL-1β, IL-8, IL-1ra and IL-1β:IL-1ra ratio throughout the entire study period (72 h, whereas levels in resistant mares returned to estrous control levels by 12 hours. Endometrial mRNA transcripts of IL-1β and IL-1ra were significantly higher in mares with heavy uterine bacterial growth compared to mares with no/mild growth. All blood parameters were unaffected by intrauterine E. coli infusion, except for a lower gene expression of IL-10 at 168 h and an increased expression of IL-1ra at 48 h observed in susceptible

  18. Inflammatory signaling compromises cell responses to interferon alpha

    Science.gov (United States)

    HuangFu, Wei-Chun; Qian, Juan; Liu, Chengbao; Liu, Jianghuai; Lokshin, Anna E.; Baker, Darren P.; Rui, Hallgeir; Fuchs, Serge Y

    2011-01-01

    Interferon alpha (IFNα) is widely used for treatment of melanoma and certain other malignancies. This cytokine as well as the related IFNβ exerts potent anti-tumorigenic effects; however, their efficacy in patients is often suboptimal. Here we report that inflammatory signaling impedes the effects of IFNα/β. Melanoma cells can secrete pro-inflammatory cytokines that inhibit cellular responses to IFNα/β via activating the ligand-independent pathway for the phosphorylation and subsequent ubiquitination and accelerated degradation of the IFNAR1 chain of Type I IFN receptor. Catalytic activity of the p38 protein kinase was required for IFNAR1 downregulation and inhibition of IFNα/β signaling induced by proinflammatory cytokines such as Interleukin 1 (IL-1). Activation of p38 kinase inversely correlated with protein levels of IFNAR1 in clinical melanoma specimens. Inhibition of p38 kinase augmented the inhibitory effects of IFNα/β on cell viability and growth in vitro and in vivo. The role of inflammation and p38 protein kinase in regulating cellular responses to IFNα/β in normal and tumor cells are discussed. PMID:21666722

  19. Increased inflammatory response in cytomegalovirus seropositive patients with Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Gabriel Westman

    Full Text Available Alzheimer's disease (AD has been associated with increased local inflammation in the affected brain regions, and in some studies also with elevated levels of proinflammatory cytokines in peripheral blood. Cytomegalovirus (CMV is known to promote a more effector-oriented phenotype in the T-cell compartment, increasing with age. The aim of this study was to investigate the inflammatory response of peripheral blood mononuclear cells (PBMCs from AD patients and non-demented (ND controls. Using a multiplex Luminex xMAP assay targeting GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IP-10 and TNF-α, cytokine profiles from PBMCs were analysed after stimulation with anti-CD3/CD28 beads, CMV pp65 peptide mix or amyloid β (Aβ protofibrils, respectively. CMV seropositive AD subjects presented with higher IFN-γ levels after anti-CD3/CD28 and CMV pp65 but not after Aβ stimulation, compared to CMV seropositive ND controls. When analysing IFN-γ response to anti-CD3/CD28 stimulation on a subgroup level, CMV seropositive AD subjects presented with higher levels compared to both CMV seronegative AD and CMV seropositive ND subjects. Taken together, our data from patients with clinically manifest AD suggest a possible role of CMV as an inflammatory promoter in AD immunology. Further studies of AD patients at earlier stages of disease, could provide better insight into the pathophysiology.

  20. Effect of ghrelin on inflammatory response in lung contusion

    Directory of Open Access Journals (Sweden)

    Berrak Guven

    2013-02-01

    Full Text Available The purpose of this study was to investigate the effects of ghrelin on inflammatory response and tissue damage following trauma-induced acute lung injury. Thirty male wistar albino rats (300–400 g were randomly assigned into three groups: control group (n = 6, lung contusion plus saline (saline-treated, n = 12, and lung contusion plus ghrelin (ghrelin-treated, n = 12. Saline- or ghrelin-treated traumatic rats were sacrificed at two time points (24 and 72 hours after lung contusion. Blood was collected for the analysis of serum adenosine deaminase (ADA. Tissue transforming growth factor-beta 1 (TGF-β1 and matrix metalloproteinase-2 (MMP-2 levels were measured by enzyme-linked immunosorbent assay and histopathological examination was performed on the lung tissue samples. Our results indicated that ghrelin significantly reduced morphologic damages. Serum ADA activities were significantly decreased after lung contusion and this decline started early with ghrelin treatment. TGF-β1 and MMP-2 levels in lung tissue were elevated at 72 hours after lung contusion and treatment with ghrelin significantly increased TGF-β1 level and reduced MMP-2 level. In conclusion, our study demonstrates that acute lung injury initiated proinflammatory responses and ghrelin administration showed an anti-inflammatory effect in lung contusion.

  1. Inflammatory and Bone Remodeling Responses to the Cytolethal Distending Toxins

    Directory of Open Access Journals (Sweden)

    Georgios N. Belibasakis

    2014-04-01

    Full Text Available The cytolethal distending toxins (CDTs are a family of exotoxins produced by a wide range of Gram-negative bacteria. They are known for causing genotoxic stress to the cell, resulting in growth arrest and eventually apoptotic cell death. Nevertheless, there is evidence that CDTs can also perturb the innate immune responses, by regulating inflammatory cytokine production and molecular mediators of bone remodeling in various cell types. These cellular and molecular events may in turn have an effect in enhancing local inflammation in diseases where CDT-producing bacteria are involved, such as Aggregatibacter actinomycetemcomitans, Haemophilus ducreyi, Campylobacter jejuni and Helicobacter hepaticus. One special example is the induction of pathological bone destruction in periodontitis. The opportunistic oral pathogen Aggregatibatcer actinoycemetemcomitans, which is involved in the aggressive form of the disease, can regulate the molecular mechanisms of bone remodeling in a manner that favors bone resorption, with the potential involvement of its CDT. The present review provides an overview of all known to-date inflammatory or bone remodeling responses of CDTs produced by various bacterial species, and discusses their potential contribution to the pathogenesis of the associated diseases.

  2. Toxoplasma gondii effectors are master regulators of the inflammatory response

    Science.gov (United States)

    Melo, Mariane B.; Jensen, Kirk D.C.; Saeij, Jeroen P.J.

    2011-01-01

    Toxoplasma is a highly successful parasite that establishes a life-long chronic infection. To do this it must carefully regulate immune activation and host cell effector mechanisms. Here we review the latest developments in our understanding of how Toxoplasma counteracts the host’s immune response, and in some cases provokes it, through the use of specific parasite effector proteins. An emerging theme from these discoveries is that Toxoplasma effectors are master regulators of the pro-inflammatory response, which elicits many of the host’s toxoplasmacidal mechanisms. We speculate that combinations of these effectors present in certain Toxoplasma strains work to maintain an optimal parasite burden in different hosts to ensure parasite transmission. PMID:21893432

  3. Inflammatory response in laparoscopic vs. open surgery for gastric cancer

    DEFF Research Database (Denmark)

    Okholm, Cecilie; Goetze, Jens Peter; Svendsen, Lars Bo

    2014-01-01

    lead to an increased susceptibility to complications and morbidity. The aim of this review was to investigate if laparoscopic surgery reduces the immunological response compared to open surgery in gastric cancer. METHODS: We conducted a literature search identifying relevant studies comparing...... laparoscopy or laparoscopic-assisted surgery with open gastric surgery. The main outcome was postoperative immunological status defined as surgical stress parameters, including inflammatory cytokines and blood parameters. RESULTS: We identified seven studies that addressed the immunological status in patients...... laparotomy. Finally, most studies reported lower levels of white blood cell count in laparoscopic patients, although this result did not reach statistical significance in a small number of studies. CONCLUSIONS: Laparoscopy-assisted gastric surgery seems to attenuate the immune response compared to open...

  4. Iodinated contrast media alter immune responses in pro-inflammatory states.

    LENUS (Irish Health Repository)

    O'Donnell, David H

    2010-07-01

    Hypertonic saline causes a transient elevation of blood osmolality and has been shown to alter cellular inflammatory responses in pro-inflammatory states. Intravascular administration of iodine contrast media also causes a transient elevation of blood osmolarity.

  5. Corporate Social Responsibility and Sustainability in Danish Public Procurement

    DEFF Research Database (Denmark)

    Andrecka, Marta

    2017-01-01

    . Secondly, as Denmark has been known as a pioneer in sustainable development, including implementation of it in public purchasing this article focuses on recent developments in the areas of CSR and sustainable public procurement in Denmark, and analyses relevant Danish Public Procurement Complaints Board......The new EU Procurement Directives reinforced the importance of sustainable development by facilitating the strategic use of public procurement to achieve broader societal goals and as such offer significant new opportunities for sustainable public procurement. The task of today is to better...... understand the continuously developing concepts of SPP, as well as to identify the drivers and barriers that promote or hinder its further implementation. This article firstly deals with the relationship between the concepts of sustainability, Corporate Social Responsibility (CSR) and public procurement...

  6. Biotin deficiency enhances the inflammatory response of human dendritic cells.

    Science.gov (United States)

    Agrawal, Sudhanshu; Agrawal, Anshu; Said, Hamid M

    2016-09-01

    The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-α, IL-12p40, IL-23, and IL-1β compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-γ and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency.

  7. Local and Systemic Inflammatory Responses to Experimentally Induced Gingivitis

    Science.gov (United States)

    Leishman, Shaneen J.; Seymour, Gregory J.; Ford, Pauline J.

    2013-01-01

    This study profiled the local and systemic inflammatory responses to experimentally induced gingivitis. Eight females participated in a 21-day experimental gingivitis model followed by a 14-day resolution phase. Bleeding on probing and plaque index scores were assessed before, during, and after resolution of gingival inflammation, and samples of saliva, GCF, and plasma were collected. Samples were assessed for biomarkers of inflammation using the BioPlex platform and ELISA. There were no significant changes in GCF levels of cytokines during the experimental phase; however, individual variability in cytokine profiles was noted. During resolution, mean GCF levels of IL-2, IL-6, and TNF-α decreased and were significantly lower than baseline levels (P = 0.003, P = 0.025, and P = 0.007, resp.). Furthermore, changes in GCF levels of IL-2, IL-6, and TNF-α during resolution correlated with changes in plaque index scores (r = 0.88, P = 0.004; r = 0.72, P = 0.042; r = 0.79, P = 0.019, resp.). Plasma levels of sICAM-1 increased significantly during the experimental phase (P = 0.002) and remained elevated and significantly higher than baseline levels during resolution (P gingivitis adds to the systemic inflammatory burden of an individual. PMID:24227893

  8. Sustainable and responsible supply chain governance: challenges and opportunities

    NARCIS (Netherlands)

    Boström, M.; Jönsson, A.M.; Lockie, S.; Mol, A.P.J.; Oosterveer, P.J.M.

    2015-01-01

    This paper introduces the Special Volume on sustainable and responsible supply chain governance. As globalized supply chains cross multiple regulatory borders, the firms involved in these chains come under increasing pressure from consumers, NGOs and governments to accept responsibility for social

  9. Androgen deprivation modulates the inflammatory response induced by irradiation

    Directory of Open Access Journals (Sweden)

    Lin Paul-Yang

    2009-03-01

    Full Text Available Abstract Background The aim of this study was to determine whether radiation (RT-induced inflammatory responses and organ damage might be modulated by androgen deprivation therapies. Methods The mRNA and tissue sections obtained from the lungs, intestines and livers of irradiated mice with or without androgen deprivation were analyzed by real-time PCR and histological analysis. Activation of NF-kappa B was examined by measuring nuclear protein levels in the intestine and lung 24 h after irradiation. We also examined the levels of cyclooxygenase-2 (COX-2, TGF-β1 and p-AKT to elucidate the related pathway responsible to irradiation (RT -induced fibrosis. Results We found androgen deprivation by castration significantly augmented RT-induced inflammation, associated with the increase NF-κB activation and COX-2 expression. However, administration of flutamide had no obvious effect on the radiation-induced inflammation response in the lung and intestine. These different responses were probably due to the increase of RT-induced NF-κB activation and COX-2 expression by castration or lupron treatment. In addition, our data suggest that TGF-β1 and the induced epithelial-mesenchymal transition (EMT via the PI3K/Akt signaling pathway may contribute to RT-induced fibrosis. Conclusion When irradiation was given to patients with total androgen deprivation, the augmenting effects on the RT-induced inflammation and fibrosis should take into consideration for complications associated with radiotherapy.

  10. Childhood Abuse and Inflammatory Responses to Daily Stressors

    Science.gov (United States)

    Gouin, Jean-Philippe; Glaser, Ronald; Malarkey, William B.; Beversdorf, David; Kiecolt-Glaser, Janice

    2013-01-01

    Background Childhood abuse leads to greater morbidity and mortality in adulthood. Dysregulated physiological stress responses may underlie the greater health risk among abused individuals. Purpose This study evaluated the impact of childhood abuse on inflammatory responses to naturalistically occurring daily stressors. Methods In this cross-sectional study of 130 older adults, recent daily stressors and childhood abuse history were evaluated using the Daily Inventory of Stressful Events and the Childhood Trauma Questionnaire. Blood samples provided data on circulating interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP). Results Childhood abuse history moderated IL-6 levels, but not TNF-α and CRP responses to daily stressors. Individuals with a childhood abuse history who experienced multiple stressors in the past 24 hours had IL-6 levels 2.35 times greater than those of participants who reported multiple daily stressors but no early abuse history. Conclusion Childhood abuse substantially enhances IL-6 responses to daily stressors in adulthood. PMID:22714139

  11. Regulation of inflammatory responses by IL-17F

    Science.gov (United States)

    Yang, Xuexian O.; Chang, Seon Hee; Park, Heon; Nurieva, Roza; Shah, Bhavin; Acero, Luis; Wang, Yi-Hong; Schluns, Kimberly S.; Broaddus, Russell R.; Zhu, Zhou; Dong, Chen

    2008-01-01

    Although interleukin (IL) 17 has been extensively characterized, the function of IL-17F, which has an expression pattern regulated similarly to IL-17, is poorly understood. We show that like IL-17, IL-17F regulates proinflammatory gene expression in vitro, and this requires IL-17 receptor A, tumor necrosis factor receptor–associated factor 6, and Act1. In vivo, overexpression of IL-17F in lung epithelium led to infiltration of lymphocytes and macrophages and mucus hyperplasia, similar to observations made in IL-17 transgenic mice. To further understand the function of IL-17F, we generated and analyzed mice deficient in IL-17F or IL-17. IL-17, but not IL-17F, was required for the initiation of experimental autoimmune encephalomyelitis. Mice deficient in IL-17F, but not IL-17, had defective airway neutrophilia in response to allergen challenge. Moreover, in an asthma model, although IL-17 deficiency reduced T helper type 2 responses, IL-17F–deficient mice displayed enhanced type 2 cytokine production and eosinophil function. In addition, IL-17F deficiency resulted in reduced colitis caused by dextran sulfate sodium, whereas IL-17 knockout mice developed more severe disease. Our results thus demonstrate that IL-17F is an important regulator of inflammatory responses that seems to function differently than IL-17 in immune responses and diseases. PMID:18411338

  12. The Role of Protein Arginine Methyltransferases in Inflammatory Responses

    Directory of Open Access Journals (Sweden)

    Ji Hye Kim

    2016-01-01

    Full Text Available Protein arginine methyltransferases (PRMTs mediate the methylation of a number of protein substrates of arginine residues and serve critical functions in many cellular responses, including cancer development, progression, and aggressiveness, T-lymphocyte activation, and hepatic gluconeogenesis. There are nine members of the PRMT family, which are divided into 4 types (types I–IV. Although most PRMTs do not require posttranslational modification (PTM to be activated, fine-tuning modifications, such as interactions between cofactor proteins, subcellular compartmentalization, and regulation of RNA, via micro-RNAs, seem to be required. Inflammation is an essential defense reaction of the body to eliminate harmful stimuli, including damaged cells, irritants, or pathogens. However, chronic inflammation can eventually cause several types of diseases, including some cancers, atherosclerosis, rheumatoid arthritis, and periodontitis. Therefore, inflammation responses should be well modulated. In this review, we briefly discuss the role of PRMTs in the control of inflammation. More specifically, we review the roles of four PRMTs (CARM1, PRMT1, PRMT5, and PRMT6 in modulating inflammation responses, particularly in terms of modulating the transcriptional factors or cofactors related to inflammation. Based on the regulatory roles known so far, we propose that PRMTs should be considered one of the target molecule groups that modulate inflammatory responses.

  13. What does sustainability mean in the HIV and AIDS response?

    Science.gov (United States)

    Oberth, Gemma; Whiteside, Alan

    2016-01-01

    Immense progress has been made in the fight against HIV and AIDS. Achieving and exceeding the AIDS targets for the Millennium Development Goals (MDGs) was accomplished, in large part, due to an unprecedented financial investment from the international community. Following an $800 million dip in donor disbursements in 2010, the discourse has since shifted to the need for greater sustainability of funding. But what does sustainability mean? Current efforts focus heavily on fiscal imperatives such as increasing domestic funding. This is important - needs are increasing at a faster rate than donor funding, especially with increased treatment coverage. The problem is that measures of financial sustainability tell very little about the actual sustainability of specific programmes, disease trajectories or enabling environments. Recognising that current definitions of sustainability lack clarity and depth, we offer a new six-tenet conceptualisation of what sustainability means in the HIV and AIDS response: (1) financial, (2) epidemiological, (3) political, (4) structural, (5) programmatic, and (6) human rights. Based on these, we examine examples of donor transitions for their approach to sustainability, including PEPFAR in South Africa, the Global Fund in Eastern Europe, and the Bill and Melinda Gates Foundation in India (Avahan). We conclude that sustainability must be understood within a broader framework beyond funding stability. We also recommend that certain interventions, such as programming for key populations, may have to continue to receive external support even if affected countries can afford to pay.

  14. Role of Apoptosis in Amplifying Inflammatory Responses in Lung Diseases

    Directory of Open Access Journals (Sweden)

    E.P. Schmidt

    2010-07-01

    Full Text Available Apoptosis is an important contributor to the pathophysiology of lung diseases such as acute lung injury (ALI and chronic obstructive pulmonary disease (COPD. Furthermore, the cellular environment of these acute and chronic lung diseases favors the delayed clearance of apoptotic cells. This dysfunctional efferocytosis predisposes to the release of endogenous ligands from dying cells. These so-called damage-associated molecular patterns (DAMPs play an important role in the stimulation of innate immunity as well as in the induction of adaptive immunity, potentially against autoantigens. In this review, we explore the role of apoptosis in ALI and COPD, with particular attention to the contribution of DAMP release in augmenting the inflammatory response in these disease states.

  15. Role of Apoptosis in Amplifying Inflammatory Responses in Lung Diseases

    Directory of Open Access Journals (Sweden)

    E.P. Schmidt

    2010-01-01

    Full Text Available Apoptosis is an important contributor to the pathophysiology of lung diseases such as acute lung injury (ALI and chronic obstructive pulmonary disease (COPD. Furthermore, the cellular environment of these acute and chronic lung diseases favors the delayed clearance of apoptotic cells. This dysfunctional efferocytosis predisposes to the release of endogenous ligands from dying cells. These so-called damage-associated molecular patterns (DAMPs play an important role in the stimulation of innate immunity as well as in the induction of adaptive immunity, potentially against autoantigens. In this review, we explore the role of apoptosis in ALI and COPD, with particular attention to the contribution of DAMP release in augmenting the inflammatory response in these disease states.

  16. Systemic inflammatory responses following welding inhalation challenge test.

    Science.gov (United States)

    Kauppi, Paula; Järvelä, Merja; Tuomi, Timo; Luukkonen, Ritva; Lindholm, Tuula; Nieminen, Riina; Moilanen, Eeva; Hannu, Timo

    2015-01-01

    The aim of this study was to investigate inflammatory and respiratory responses to welding fume exposure in patients with suspected occupational asthma. Sixteen patients referred to the Finnish Institute of Occupational Health underwent mild steel (MS) and stainless steel (SS) welding challenge tests, due to suspicion of OA. Platelet count, leucocytes and their differential count, hemoglobin, sensitive CRP, lipids, glucose and fibrinogen were analyzed in addition to interleukin (IL)-1β, IL-6, IL-8, TNF-α, endothelin-1, and E-selectin in plasma samples. Peak expiratory flow (PEF), forced expiratory volume in 1 min (FEV 1 ) and exhaled nitric oxide (NO) measurements were performed before and after the challenge test. Personal particle exposure was assessed using IOM and a mini sampler. Particle size distribution was measured by an Electric Low Pressure Impactor (ELPI). The number of leukocytes, neutrophils, and platelets increased significantly, and the hemoglobin level and number of erythrocytes decreased significantly after both the MS and SS exposure tests. Five of the patients were diagnosed with OA, and their maximum fall in FEV 1 values was 0.70 l (±0.32) 4 h after SS exposure. MS welding generated an average inhalable particle mass concentration of 31.6, and SS welding of 40.2 mg/m 3 . The mean particle concentration measured inside the welding face shields by the mini sampler was 30.2 mg/m 3 and 41.7 mg/m 3 , respectively. Exposure to MS and SS welding fume resulted in a mild systemic inflammatory response. The particle concentration from the breathing zones correlated with the measurements inside the welding face shields.

  17. Cryptosporidiosis stimulates an inflammatory intestinal response in malnourished Haitian children.

    Science.gov (United States)

    Kirkpatrick, Beth D; Daniels, Michelle M; Jean, Simone Sonia; Pape, Jean W; Karp, Christopher; Littenberg, Benjamin; Fitzgerald, Daniel W; Lederman, Howard M; Nataro, James P; Sears, Cynthia L

    2002-07-01

    The mechanisms by which Cryptosporidium parvum cause persistent diarrhea and increased morbidity and mortality are poorly understood. Three groups of Haitian children <18 months old were studied: case patients, children with diarrhea not due to Cryptosporidium, and healthy control subjects. Compared with both control groups, children with acute cryptosporidiosis were more malnourished (including measures of stunting [P=.03] and general malnutrition [P=.01]), vitamin A deficient (P=.04), and less often breast-fed (P=.04). Markers of a proinflammatory immune response, interleukin (IL)-8 and tumor necrosis factor-alpha receptor I, were significantly elevated in the case population (P=.02 and P<.01, respectively), as was fecal lactoferrin (P=.01) and the T helper (Th)-2 cytokine IL-13 (P=.03). The counterregulatory cytokine IL-10 was exclusively elevated in the case population (P<.01). A Th1 cytokine response to infection was not detected. This triple cohort study demonstrates that malnourished children with acute cryptosporidiosis mount inflammatory, Th-2, and counterregulatory intestinal immune responses.

  18. Corporate Social Responsibility And Sustainability In Romanian Commercial Banks

    OpenAIRE

    Vasile Cocris; Andra Lavinia Nichitean

    2010-01-01

    The research paper aims to underline the importance of civic behavior in business and bank’s role in the implementation of sound principles of corporate social responsibility. The authors analyzed terms such as corporate social responsibility, sustainable development, fi-nancial stability and the relationship between them, in order to explain their impact on the proper function of world economy. The authors provided a synthesis of corporate social responsibility principles and codes of con-du...

  19. Immune and inflammatory responses of Australian firefighters after repeated exposures to the heat.

    Science.gov (United States)

    Walker, Anthony; Keene, Toby; Argus, Christos; Driller, Matthew; Guy, Joshua H; Rattray, Ben

    2015-01-01

    When firefighters work in hot conditions, altered immune and inflammatory responses may increase the risk of a cardiac event. The present study aimed to establish the time course of such responses. Forty-two urban firefighters completed a repeat work protocol in a heat chamber (100 ± 5°C). Changes to leukocytes, platelets, TNFα, IL-6, IL-10, LPS and CRP were evaluated immediately post-work and also after 1 and 24 h of rest. Increases in core temperatures were associated with significant increases in leukocytes, platelets and TNFα directly following work. Further, platelets continued to increase at 1 h (+31.2 ± 31.3 × 10(9) l, p work tasks in the heat. This is particularly relevant during multi-day deployments following natural disasters. Practitioner Summary: Firefighters regularly re-enter fire affected buildings or are redeployed to further operational tasks. Should work in the heat lead to sustained immune and inflammatory changes following extended rest periods, incident controllers should plan appropriate work/rest cycles to minimise these changes and any subsequent risks of cardiac events.

  20. Value Creation in the Context of Sustainable Corporate Social Responsibility

    Directory of Open Access Journals (Sweden)

    Šmida Ľubomír

    2014-12-01

    Full Text Available Under the influence of the new rules of the economy and the society, companies are achieving a notional line of a necessary change in the approach to creating new value, wealth. Implementation of changes in the system of wealth creation requires a review of existing assumptions of unlimited growth of the global economy and wealth creation in the environment accepting economic interests, society and the environment as a holistic unit. The main purpose of this paper is the clarification of a new requirements for business, presentation of the questionnaire survey Sustainable Corporate Social Responsibility and inform on value creation in the context of Sustainable Corporate Social Responsibility.

  1. Value Creation in the Context of Sustainable Corporate Social Responsibility

    Science.gov (United States)

    Šmida, Ľubomír; Sakál, Peter

    2014-12-01

    Under the influence of the new rules of the economy and the society, companies are achieving a notional line of a necessary change in the approach to creating new value, wealth. Implementation of changes in the system of wealth creation requires a review of existing assumptions of unlimited growth of the global economy and wealth creation in the environment accepting economic interests, society and the environment as a holistic unit. The main purpose of this paper is the clarification of a new requirements for business, presentation of the questionnaire survey Sustainable Corporate Social Responsibility and inform on value creation in the context of Sustainable Corporate Social Responsibility.

  2. SUSTAINABILITY AS A STRATEGY OF RESPONSIBLE AND COMPETITIVE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    José G. Vargas-Hernández

    2012-12-01

    Full Text Available The aim of this paper is to analyze a competitiveness strategy based on sustainability to lead the way to a model of responsible and competitive development. The analysis takes as its starting point the assumption that the maturity of a sustainable business strategy positively affects competitiveness. The used method is the critical analysis. Among other results of this analysis concludes that the current business strategy seeks a system ecologically appropriate, economically viable and socially fair to reach sustainable equilibrium. This strategy based on sustainability must be promoted by the institutions and strengthened by the capabilities and resources that each company counts on to develop advantages to foster the overall development and achieve the maximization of benefits from the tangible and intangible perspectives

  3. Long-term ethanol intoxication reduces inflammatory responses in rats

    Directory of Open Access Journals (Sweden)

    E.M. Carvalho

    2005-01-01

    Full Text Available The anti-inflammatory effects of long-term ethanol intoxication were determined during ethanol treatment and withdrawal on the basis of neutrophil and eosinophil migration, hind paw edema and mast cell degranulation. Male Wistar rats (180-200 g, around 2 months of age were exposed to increasing concentrations of ethanol vapor over a 10-day period. One group was evaluated immediately after exposure (treated group - intoxicated, and another was studied 7 h later (withdrawal group. Ethanol inhalation treatment significantly inhibited carrageenan- (62% for the intoxicated group, N = 5, and 35% for the withdrawal group, N = 6 and dextran-induced paw edema (32% for intoxicated rats and 26% for withdrawal rats, N = 5 per group. Ethanol inhalation significantly reduced carrageenan-induced neutrophil migration (95% for intoxicated rats and 41% for withdrawn rats, N = 6 per group into a subcutaneous 6-day-old air pouch, and Sephadex-induced eosinophil migration to the rat peritoneal cavity (100% for intoxicated rats and 64% for withdrawn rats, N = 6 per group. A significant decrease of mast cell degranulation was also demonstrated (control, 82%; intoxicated, 49%; withdrawn, 51%, N = 6, 6 and 8, respectively. Total leukocyte and neutrophil counts in venous blood increased significantly during the 10 days of ethanol inhalation (leukocytes, 13, 27 and 40%; neutrophils, 42, 238 and 252%, respectively, on days 5, 9 and 10, N = 7, 6 and 6. The cell counts decreased during withdrawal, but were still significantly elevated (leukocytes, 10%; neutrophils, 246%, N = 6. These findings indicate that both the cellular and vascular components of the inflammatory response are compromised by long-term ethanol intoxication and remain reduced during the withdrawal period.

  4. Maresin 1 Mitigates Inflammatory Response and Protects Mice from Sepsis

    Directory of Open Access Journals (Sweden)

    Ruidong Li

    2016-01-01

    Full Text Available Sepsis, frequently caused by infection of bacteria, is considered as an uncontrollable systematic inflammation response syndrome (SIRS. Maresin 1 (Mar1 is a new proresolving mediator with potent anti-inflammatory effect in several animal models. However, its effect in sepsis is still not investigated. To address this question, we developed sepsis model in BALB/c mice by cecal ligation and puncture (CLP with or without Mar1 treatment. Our data showed that Mar1 markedly improved survival rate and decreased the levels of proinflammatory cytokines in CLP mice such as interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and interleukin-1β (IL-1β. Furthermore, Mar1 reduced serum level of lipopolysaccharide (LPS and enhanced the bacteria clearance in mice sepsis model. Moreover, Mar1 attenuated lung injury and decreased level of alanine transaminase (ALT, aspartate transaminase (AST, creatinine (Cre, and blood urea nitrogen (BUN in serum in mice after CLP surgery. Treatment with Mar1 inhibited activation of nuclear factor kappa B (NF-κb pathway. In conclusion, Mar1 exhibited protective effect in sepsis by reducing LPS, bacteria burden in serum, inhibiting inflammation response, and improving vital organ function. The possible mechanism is partly involved in inhibition of NF-κb activation.

  5. A Collaborative Programme in Sustainability and Social Responsibility

    Science.gov (United States)

    Albareda Tiana, Silvia; Alférez Villarreal, Azul

    2016-01-01

    Purpose: The purpose of this paper is to collect methodological strategies used in the training of future teachers to develop competences in sustainability and social responsibility (SSR). The proposal in this paper is to show how students learn and develop competences by performing practical activities and through a collaborative experience,…

  6. Lesion Neuroanatomy of the Sustained Attention to Response Task

    Science.gov (United States)

    Molenberghs, Pascal; Gillebert, Celine R.; Schoofs, Hanne; Dupont, Patrick; Peeters, Ronald; Vandenberghe, Rik

    2009-01-01

    The Sustained Attention to Response task is a classical neuropsychological test that has been used by many centres to characterize the attentional deficits in traumatic brain injury, ADHD, autism and other disorders. During the SART a random series of digits 1-9 is presented repeatedly and subjects have to respond to each digit (go trial) except…

  7. Altered inflammatory responsiveness in serotonin transporter mutant rats

    NARCIS (Netherlands)

    Macchi, F.; Homberg, J.R.; Calabrese, F.; Zecchillo, C.; Racagni, G.; Riva, M.A.; Molteni, R.

    2013-01-01

    BACKGROUND: Growing evidence suggests that alterations of the inflammatory/immune system contribute to the pathogenesis of depression. Indeed, depressed patients exhibit increased levels of inflammatory markers in both the periphery and the brain, and high comorbidity exists between major depression

  8. Tourniquet-induced systemic inflammatory response in extremity surgery.

    LENUS (Irish Health Repository)

    Wakai, A

    2012-02-03

    BACKGROUND: Tourniquet-induced reperfusion injury in animals produces significant systemic inflammatory effects. This study investigated whether a biologic response occurs in a clinically relevant model of tourniquet-induced reperfusion injury. METHODS: Patients undergoing elective knee arthroscopy were prospectively randomized into controls (no tourniquet) and subjects (tourniquet-controlled). The effects of tourniquet-induced reperfusion on monocyte activation state, neutrophil activation state, and transendothelial migration (TEM) were studied. Changes in the cytokines implicated in reperfusion injury, tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-10 were also determined. RESULTS: After 15 minutes of reperfusion, neutrophil and monocyte activation were significantly increased. Pretreatment of neutrophils with pooled subject (ischemia-primed) plasma significantly increased TEM. In contrast, TEM was not significantly altered by ischemia-primed plasma pretreatment of the endothelial monolayer. Significant elevation of tumor necrosis factor-alpha and IL-1beta were observed in subjects compared with controls after 15 minutes of reperfusion. There was no significant difference in serum IL-10 levels between the groups at all the time points studied. CONCLUSION: These results indicate a transient neutrophil and monocyte activation after tourniquet-ischemia that translates into enhanced neutrophil transendothelial migration with potential for tissue injury.

  9. Two opposite extremes of adiposity similarly reduce inflammatory response of antigen-induced acute joint inflammation

    NARCIS (Netherlands)

    Oliveira, M.C.; Silveira, A.L.; Tavares, L.P.; Rodrigues, D.F.; Loo, F.A.J. van de; Sousa, L.P.; Teixeira, M.M.; Amaral, F.A.; Ferreira, A.V.

    2017-01-01

    OBJECTIVE: Acute inflammation is a normal response of tissue to an injury. During this process, inflammatory mediators are produced and metabolic alterations occur. Adipose tissue is metabolically activated, and upon food consumption, it disrupts the inflammatory response. However, little is known

  10. The effect of dietary fatty acids on post-operative inflammatory response in a porcine model

    DEFF Research Database (Denmark)

    Langerhuus, Sine Nygaard; Jensen, Karin Hjelholt; Tønnesen, Else Kirstine

    2012-01-01

    ), sunflower oil (SO, n 28), or animal fat (AF, n 28) was evaluated with respect to post-operative responses in inflammatory markers in a porcine model on aortic vascular prosthetic graft infection. In the early post-operative period (0 ...-operative response in a number of inflammatory markers was affected by FO, and this was most apparent compared with SO....

  11. Myeloperoxidase modulates lung epithelial responses to pro-inflammatory agents

    NARCIS (Netherlands)

    Haegens, A.; Vernooy, J. H. J.; Heeringa, P.; Mossman, B. T.; Wouters, E. F. M.

    During extensive inflammation, neutrophils undergo secondary necrosis causing myeloperoxidase (MPO) release that may damage resident lung cells. Recent observations suggest that MPO has pro-inflammatory properties, independent of its enzymatic activity. The aims of the present study were to

  12. Systemic inflammatory response in acute cholangitis and after subsequent treatment

    NARCIS (Netherlands)

    Kimmings, A. N.; van Deventer, S. J.; Rauws, E. A. J.; Huibregtse, K.; Gouma, D. J.

    2000-01-01

    To measure the concentrations of endotoxin and inflammatory mediators during an attack of acute cholangitis and see what effect endoscopic treatment had on these mediators. Prospective study. University teaching hospital The Netherlands. Ten patients with acute cholangitis. Measurements were made

  13. Sustainable Urban Development Calls for Responsibility through Life Cycle Management

    Directory of Open Access Journals (Sweden)

    Miro Ristimäki

    2015-09-01

    Full Text Available Urban development bestows a great opportunity to increase sustainability in the built environment as cities are responsible for the majority of environmental impacts. However, the urban development process is fragmented and sub-optimization leads to unsustainable life cycle outcomes. The purpose of this study is to examine the urban development process from a life cycle perspective and identify how different actors understand life cycle management. By utilizing an inductive qualitative research design, 38 in-depth thematic interviews were conducted within the Finnish urban development industry including a case study and independent interviews from different phases of the urban development life cycle. The theoretical perspective is a combination of the ecosystem construct and life cycle management. Results show that there is no clear responsible actor for life cycle management in urban development. All actors claim that there is value to be added, mostly in economic, but also environmental and social terms. This study reveals that investors should be the responsible actor in the urban development process. By claiming responsibility and focusing on life cycle leadership we can improve sustainability in urban development, and respond to the urban sustainability challenge, thus improving the quality of life and welfare in our urban society.

  14. Dimethyl Fumarate Reduces Inflammatory Responses in Experimental Colitis

    Science.gov (United States)

    Casili, Giovanna; Cordaro, Marika; Impellizzeri, Daniela; Bruschetta, Giuseppe; Paterniti, Irene; Cuzzocrea, Salvatore

    2016-01-01

    Background and Aims: Fumaric acid esters have been proven to be effective for the systemic treatment of psoriasis and multiple sclerosis. We aimed to develop a new treatment for colitis. Methods: We investigated the effect of dimethylfumarate [DMF, 10-30-100mg/kg] on an experimental model of colitis induced by dinitrobenzene sulphuric acid [DNBS]. We also evaluated the therapeutic activity of 7 weeks’ treatment with DMF [30mg/kg] on 9-week-old IL-10KO mice that spontaneously develop a T helper-1 [Th1]-dependent chronic enterocolitis after birth, that is fully established at 8–10 weeks of age. The mechanism of this pharmacological potential of DMF [10 μM] was investigated in colonic epithelial cell monolayers [Caco-2] exposed to H2O2. The barrier function was evaluated by the tight junction proteins. Results: The treatment with DMF significantly reduced the degree of haemorrhagic diarrhoea and weight loss caused by administration of DNBS. DMF [30 and 100mg/kg] also caused a substantial reduction in the degree of colon injury, in the rise in myeloperoxidase [MPO] activity, and in the increase in tumour necrosis factor [TNF]-α expression, as well as in the up-regulation of ICAM-1 caused by DNBS in the colon. Molecular studies demonstrated that DMF impaired NF-κB signalling via reduced p65 nuclear translocalisation. DMF induced a stronger antioxidant response as evidenced by a higher expression of Mn-superoxide dismutase. Moreover, DMF protected human intestinal epithelial cells against H2O2-induced barrier dysfunction, restoring ZO-1 occludin expression, via the HO-1 pathway. Conclusions: DMF treatment reduces the degree of colitis caused by DNBS. We propose that DMF treatment may be useful in the treatment of inflammatory bowel disease. PMID:26690241

  15. Lactic acid delays the inflammatory response of human monocytes

    Energy Technology Data Exchange (ETDEWEB)

    Peter, Katrin, E-mail: katrin.peter@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Rehli, Michael, E-mail: michael.rehli@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); RCI Regensburg Center for Interventional Immunology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Singer, Katrin, E-mail: katrin.singer@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Renner-Sattler, Kathrin, E-mail: kathrin.renner-sattler@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Kreutz, Marina, E-mail: marina.kreutz@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); RCI Regensburg Center for Interventional Immunology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany)

    2015-02-13

    Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (AKT) as well as the degradation of IκBα. Consistently, the LPS-induced nuclear accumulation of NFκB was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. - Highlights: • Lactic acid broadly delays LPS-induced gene expression in human monocytes. • Expression of important monocyte effector molecules is affected by lactic acid. • Interference of lactic acid with TLR signaling causes the delayed gene expression. • The profound effect of lactic acid might contribute to immune suppression in tumors.

  16. Dexamethasone Enhances ATP-Induced Inflammatory Responses in Endothelial Cells

    Science.gov (United States)

    Ding, Yi; Gao, Zhan-Guo; Jacobson, Kenneth A.

    2010-01-01

    The purinergic nucleotide ATP is released from stressed cells and is implicated in vascular inflammation. Glucocorticoids are essential to stress responses and are used therapeutically, yet little information is available that describes the effects of glucocorticoids on ATP-induced inflammation. In a human microvascular endothelial cell line, extracellular ATP-induced interleukin (IL)-6 secretion in a dose- and time-dependent manner. When cells were pretreated with dexamethasone, a prototypic glucocorticoid, ATP-induced IL-6 production was enhanced in a time- and dose-dependent manner. Mifepristone, a glucocorticoid receptor antagonist, blocked these effects. ATP-induced IL-6 release was significantly inhibited by a phospholipase C inhibitor [1-[6-[((17β)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione (U73122)] (63.2 ± 3%, p dexamethasone induced mRNA expression of the purinergic P2Y2 receptor (P2Y2R) 1.8- ± 0.1-fold and, when stimulated with ATP, enhanced Ca2+ release and augmented IL-6 mRNA expression. Silencing of the P2Y2R by its small interfering RNA decreased ATP-induced IL-6 production by 81 ± 1% (p Dexamethasone enhanced the transcription rate of P2Y2R mRNA and induced a dose-related increase in the activity of the P2Y2R promoter. Furthermore, dexamethasone-enhanced ATP induction of adhesion molecule transcription and augmented the release of IL-8. Dexamethasone leads to an unanticipated enhancement of endothelial inflammatory mediator production by extracellular ATP via a P2Y2R-dependent mechanism. These data define a novel positive feedback loop of glucocorticoids and ATP-induced endothelial inflammation. PMID:20826566

  17. Lactic acid delays the inflammatory response of human monocytes.

    Science.gov (United States)

    Peter, Katrin; Rehli, Michael; Singer, Katrin; Renner-Sattler, Kathrin; Kreutz, Marina

    2015-02-13

    Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (AKT) as well as the degradation of IκBα. Consistently, the LPS-induced nuclear accumulation of NFκB was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Modulation of inflammatory and immune responses by vitamin D.

    Science.gov (United States)

    Colotta, Francesco; Jansson, Birger; Bonelli, Fabrizio

    2017-12-01

    Vitamin D (VitD) is a prohormone most noted for the regulation of calcium and phosphate levels in circulation, and thus of bone metabolism. Inflammatory and immune cells not only convert inactive VitD metabolites into calcitriol, the active form of VitD, but also express the nuclear receptor of VitD that modulates differentiation, activation and proliferation of these cells. In vitro, calcitriol upregulates different anti-inflammatory pathways and downregulates molecules that activate immune and inflammatory cells. Administration of VitD has beneficial effects in a number of experimental models of autoimmune disease. Epidemiologic studies have indicated that VitD insufficiency is frequently associated with immune disorders and infectious diseases, exacerbated by increasing evidence of suboptimal VitD status in populations worldwide. To date, however, most interventional studies in human inflammatory and immune diseases with VitD supplementation have proven to be inconclusive. One of the reasons could be that the main VitD metabolite measured in these studies was the 25-hydroxyVitD (25OHD) rather than its active form calcitriol. Although our knowledge of calcitriol as modulator of immune and inflammatory reactions has dramatically increased in the past decades, further in vivo and clinical studies are needed to confirm the potential benefits of VitD in the control of immune and inflammatory conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Academic-community partnerships for sustainable preparedness and response systems.

    Science.gov (United States)

    Isakov, Alexander; O'Neal, Patrick; Prescott, John; Stanley, Joan; Herrmann, Jack; Dunlop, Anne

    2014-01-01

    Academic institutions possess tremendous resources that could be important for community disaster response and preparedness activities. In-depth exploration of the role of academic institutions in community disaster response has elicited information about particular academic resources leveraged for and essential to community preparedness and response; factors that contribute to the decision-making process for partner engagement; and facilitators of and barriers to sustainable collaborations from the perspectives of academic institutions, public health and emergency management agencies, and national association and agency leaders. The Academic-Community Partnership Project of the Emory University Preparedness and Emergency Response Research Center in collaboration with the Association of Schools of Public Health convened an invitational summit which included leadership from the National Association of County and City Health Officials, Association of State and Territorial Health Officials, Directors of Public Health Preparedness, Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response, CDC Office of Public Health Preparedness and Response, Association of Schools of Public Health, Association of American Medical Colleges, Association of Academic Health Centers, American Association of Colleges of Nursing, Council of State and Territorial Epidemiologists, and American Association of Poison Control Centers. From this convention, emerged recommendations for building and sustaining academic-public health-community collaborations for preparedness locally and regionally.

  20. Sustained Interleukin-1β Exposure Modulates Multiple Steps in Glucocorticoid Receptor Signaling, Promoting Split-Resistance to the Transactivation of Prominent Anti-Inflammatory Genes by Glucocorticoids

    Directory of Open Access Journals (Sweden)

    Pedro Escoll

    2015-01-01

    Full Text Available Clinical treatment with glucocorticoids (GC can be complicated by cytokine-induced glucocorticoid low-responsiveness (GC-resistance, GCR, a condition associated with a homogeneous reduction in the expression of GC-receptor- (GR- driven anti-inflammatory genes. However, GR level and phosphorylation changes modify the expression of individual GR-responsive genes differently. As sustained IL-1β exposure is key in the pathogenesis of several major diseases with prevalent GCR, we examined GR signaling and the mRNA expression of six GR-driven genes in cells cultured in IL-1β and afterwards challenged with GC. After a GC challenge, sustained IL-1β exposure reduced the cytoplasmic GR level, GRSer203 and GRSer211 phosphorylation, and GR nuclear translocation and led to selective GCR in the expression of the studied genes. Compared to GC alone, in a broad range of GC doses plus sustained IL-1β, FKBP51 mRNA expression was reduced by 1/3, TTP by 2/3, and IRF8 was completely knocked down. In contrast, high GC doses did not change the expression of GILZ and DUSP1, while IGFBP1 was increased by 5-fold. These effects were cytokine-selective, IL-1β dose- and IL-1R1-dependent. The integrated gain and loss of gene functions in the “split GCR” model may provide target cells with a survival advantage by conferring resistance to apoptosis, chemotherapy, and GC.

  1. Vibrio vulnificus induces mTOR activation and inflammatory responses in macrophages.

    Directory of Open Access Journals (Sweden)

    Dan-Li Xie

    Full Text Available Vibrio vulnificus (V. vulnificus, a Gram-negative marine bacterium, can cause life-threatening primary septicemia, especially in patients with liver diseases. How V. vulnificus affects the liver and how it acts on macrophages are not well understood. In this report, we demonstrated that V. vulnificus infection causes a strong inflammatory response, marked expansion of liver-resident macrophages, and liver damage in mice. We demonstrated further that V. vulnificus activates mTOR in macrophages and inhibition of mTOR differentially regulates V. vulnificus induced inflammatory responses, suggesting the possibility of targeting mTOR as a strategy to modulate V. vulnificus induced inflammatory responses.

  2. Utility of immune response-derived biomarkers in the differential diagnosis of inflammatory disorders

    NARCIS (Netherlands)

    Oever, J. ten; Netea, M.G.; Kullberg, B.J.

    2016-01-01

    Differentiating between inflammatory disorders is difficult, but important for a rational use of antimicrobial agents. Biomarkers reflecting the host immune response may offer an attractive strategy to predict the etiology of an inflammatory process and can thus be of help in decision making. We

  3. Neuroendocrine modulation of the inflammatory response in common carp: adrenaline regulates leukocyte profile and activity

    NARCIS (Netherlands)

    Kepka, M.; Verburg-van Kemenade, B.M.L.; Chadzinska, M.K.

    2013-01-01

    Inflammatory responses have to be carefully controlled, as high concentrations and/or prolonged action of inflammation-related molecules (e.g. reactive oxygen species, nitric oxide and pro-inflammatory cytokines) can be detrimental to host tissue and organs. One of the potential regulators of the

  4. Maggot secretions suppress pro-inflammatory responses of human monocytes through elevation of cyclic AMP

    NARCIS (Netherlands)

    Plas, M.P.E.; Baldry, M.; Dissel, van J.T.; Jukema, G.N.; Nibbering, P.H.

    2009-01-01

    AIMS/HYPOTHESIS: Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. As monocytes may contribute to the excessive inflammatory responses in such wounds, this study focussed on the effects of maggot secretions on the pro-inflammatory activities of these cells.

  5. The response of pre-inflammatory cytokines factors to different ...

    African Journals Online (AJOL)

    Within group comparisons (depended t student test) also showed a significant difference in IL-1b and IL-6 of endurance and concurrent groups compared to baseline. Generally, it can be concluded that endurance and concurrent exercise training in part has a positive effect on pre-inflammatory cytokines.

  6. Salicornia bigelovii Torr Attenuates Neuro-Inflammatory Responses ...

    African Journals Online (AJOL)

    BV- microglial cells were stimulated with LPS to study the protein expression and production of inflammatory mediators, determined by Western blot analysis. Results: SBE significantly inhibited the DPPH-generated free radicals showing maximum inhibition at 40 μg/mL (p < 0.001). SBE alone did not exhibit any signs of ...

  7. p120-catenin mediates inflammatory responses in the skin

    DEFF Research Database (Denmark)

    Perez-Moreno, Mirna; Davis, Michael A; Wong, Ellen

    2006-01-01

    but no overt disruption in barrier function or intercellular adhesion. As the mice age, however, they display epidermal hyperplasia and chronic inflammation, typified by hair degeneration and loss of body fat. Using skin engraftments and anti-inflammatory drugs, we show that these features are not attributable...

  8. Hesperidin supplementation modulates inflammatory responses following myocardial infarction.

    Science.gov (United States)

    Haidari, F; Heybar, H; Jalali, M T; Ahmadi Engali, K; Helli, B; Shirbeigi, E

    2015-01-01

    A growing number of studies have suggested a crucial role for a variety of inflammatory mediators in myocardial infarction. Recently, several flavonoids have been shown to have cardioprotective and anti-inflammatory properties. Therefore, the aim of this study was to investigate the effect of hesperidin-a common constituent of citrus fruits-on the serum levels of inflammatory markers and adipocytocines in patients with myocardial infarction. Seventy-five patients with myocardial infarction were participated in this randomized, double-blind controlled clinical trial and were assigned to 2 intervention and control groups. Subjects consumed 600 mg/d pure hesperidin supplement and placebo in the intervention and control groups, respectively, for 4 weeks. Serum concentrations of inflammatory markers and adipocytocines were measured at baseline and at the end of the intervention. Consumption of 600 mg/day hesperidin significantly decreased the serum levels of E-selectin and increased adiponectin and high-density lipoprotein cholesterol (HDL-C) concentrations in patients with myocardial infarction. The improvement in other inflammatory markers, such as interleukin (IL)-6, high-sensitivity C-reactive protein (hs-CRP), leptin, and other lipid profile was also observed at the end of the intervention, compared to the baseline values, but the difference between the hesperidin and placebo groups was not statistically significant (p > 0.05). Hesperidin supplementation could compensate for decreased levels of adiponectin and HDL-C and increased levels of E-selectin in patients with myocardial infarction. These results support the concept that certain flavonoids in the diet can be associated with significant health benefits, including heart health.

  9. Sustainability Ethics Emergency and Media Responsibility in the Consumption Society

    Directory of Open Access Journals (Sweden)

    Rogério Bianchi de Araujo

    2008-08-01

    Full Text Available In this article, it is discussed the sustainable development and the importance of the environmental cause, in order to create models of development that consider the sustainability and environmental preservation for the future generations. The participation of all society is essential in this debate. The establishment of new habits that do not compromise the subsistence and the conscience of the real self-destruction possibility must be studied and analysed; they consist in challenging intentions, which detach the relevance and the moral duty of the media to restore a new ethics and a new way to understand the reality, as well as to divulge the impact of this different perception in the human life. Therefore occurs the requirement of a responsible compromise relating to the development, by way of understanding the biosphere as the social life basis, considering that, in these ecosystems, the human being is only one of the many species that live in an interdependence relationship.

  10. Efficient Customer Selection for Sustainable Demand Response in Smart Grids

    Energy Technology Data Exchange (ETDEWEB)

    Zois, Vasileios; Frincu, Marc; Chelmis, Charalambos; Saeed, Muhammad Rizwan; Prasanna, Viktor K.

    2014-11-03

    Regulating the power consumption to avoid peaks in demand is a common practice. Demand Response(DR) is being used by utility providers to minimize costs or ensure system reliability. Although it has been used extensively there is a shortage of solutions dealing with dynamic DR. Past attempts focus on minimizing the load demand without considering the sustainability of the reduced energy. In this paper an efficient algorithm is presented which solves the problem of dynamic DR scheduling. Data from the USC campus micro grid were used to evaluate the efficiency as well as the robustness of the proposed solution. The targeted energy reduction is achieved with a maximum average approximation error of ≈ 0.7%. Sustainability of the reduced energy is achieved with respect to the optimal available solution providing a maximum average error less than 0.6%. It is also shown that a solution is provided with a low computational cost fulfilling the requirements of dynamic DR.

  11. Bmal1 regulates inflammatory responses in macrophages by modulating enhancer RNA transcription

    National Research Council Canada - National Science Library

    Yumiko Oishi; Shinichiro Hayashi; Takayuki Isagawa; Motohiko Oshima; Atsushi Iwama; Shigeki Shimba; Hitoshi Okamura; Ichiro Manabe

    2017-01-01

    ...) activation by modulating enhancer activity. Global transcriptome analysis indicated that deletion of Arntl perturbed the time-dependent inflammatory responses elicited by TLR4 activation by Kdo2-lipid A (KLA...

  12. Citral reduces nociceptive and inflammatory response in rodents

    Directory of Open Access Journals (Sweden)

    Lucindo J. Quintans-Júnior

    2011-06-01

    Full Text Available Citral (CIT, which contains the chiral enantiomers, neral (cis and geranial (trans, is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and anti-inflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT had significant protection (p<0.001 against acetic acid (0.8% induced nociceptive behavior and the effects were also similar to morphine while formalin induced nociception was significantly protected (p<0.05 only at higher dose (200 mg/kg of CIT in the first phase of the test. CIT significantly reduce (p<0.001 nociceptive behavior emanating from inflammation in second phase at all the doses.The pretreatment with CIT (100 and 200 mg/kg significantly reduced the paw edema induced by carrageenan. Moreover, systemic treatment with CIT (100 and 200 mg/kg significantly reduced (p<0.001 the leukocyte migration in the carrageenan-induced migration to the peritoneal cavity. Our investigation shows that CIT possess significant central and peripheral antinociceptive effects. It was also verified an anti-inflammatory activity. All together these results suggest that CIT might represent important tool for treatment of painful conditions.

  13. Citral reduces nociceptive and inflammatory response in rodents

    Directory of Open Access Journals (Sweden)

    Lucindo J. Quintans-Júnior

    2011-04-01

    Full Text Available Citral (CIT, which contains the chiral enantiomers, neral (cis and geranial (trans, is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and anti-inflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT had significant protection (p<0.001 against acetic acid (0.8% induced nociceptive behavior and the effects were also similar to morphine while formalin induced nociception was significantly protected (p<0.05 only at higher dose (200 mg/kg of CIT in the first phase of the test. CIT significantly reduce (p<0.001 nociceptive behavior emanating from inflammation in second phase at all the doses.The pretreatment with CIT (100 and 200 mg/kg significantly reduced the paw edema induced by carrageenan. Moreover, systemic treatment with CIT (100 and 200 mg/kg significantly reduced (p<0.001 the leukocyte migration in the carrageenan-induced migration to the peritoneal cavity. Our investigation shows that CIT possess significant central and peripheral antinociceptive effects. It was also verified an anti-inflammatory activity. All together these results suggest that CIT might represent important tool for treatment of painful conditions.

  14. Ginger Extract Suppresses Inflammatory Response and Maintains Barrier Function in Human Colonic Epithelial Caco-2 Cells Exposed to Inflammatory Mediators.

    Science.gov (United States)

    Kim, Yunyoung; Kim, Dong-Min; Kim, Ji Yeon

    2017-05-01

    The beneficial effects of ginger in the management of gastrointestinal disturbances have been reported. In this study, the anti-inflammatory potential of ginger extract was assessed in a cellular model of gut inflammation. In addition, the effects of ginger extract and its major active compounds on intestinal barrier function were evaluated. The response of Caco-2 cells following exposure to a mixture of inflammatory mediators [interleukin [IL]-1β, 25 ng/mL; lipopolysaccharides [LPS], 10 ng/mL; tumor necrosis factor [TNF]-α, 50 ng/mL; and interferon [INF]-γ, 50 ng/mL] were assessed by measuring the levels of secreted IL-6 and IL-8. In addition, the mRNA levels of cyclooxygenase-2 and inducible nitric oxide synthase were measured. Moreover, the degree of nuclear factor (NF)-κB inhibition was examined, and the intestinal barrier function was determined by measuring the transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC)-dextran transfer. It was observed that ginger extract and its constituents improved inflammatory responses by decreasing the levels of nitrite, PGE2, IL-6, and IL-8 via NF-κB inhibition. The ginger extract also increased the TEER and decreased the transfer of FITC-dextran from the apical side of the epithelium to the basolateral side. Taken together, these results show that ginger extract may be developed as a functional food for the maintenance of gastrointestinal health. © 2017 Institute of Food Technologists®.

  15. [Persistence of chronic inflammatory responses, role in the development of chronic pancreatitis, obesity and pancreatic cancer].

    Science.gov (United States)

    Khristich, T N

    2014-11-01

    The purpose of the review--to analyze the basic data of the role of chronic low-intensity inflammatory response as general biological process in the development and progression of chronic pancreatitis, obesity, and pancreatic cancer. Highlighted evidence from epidemiological studies showing that chronic pancreatitis and obesity are independent risk factors for pancreatic cancer, regardless of diabetes. Studied role of adipokines as Cytokines regulating of immune inflammatory response. Draws attention to the staging of pancreatic cancer in obesity.

  16. SUSTAINABILITY AND COMPANY’S CORPORATE SOCIAL RESPONSIBILITY NEED

    Directory of Open Access Journals (Sweden)

    MONICA VIOLETA ACHIM

    2012-05-01

    Full Text Available The company is a living organism, is an entity and its analysis should be made taking into account the whole system. The company is a dynamic environment, which has as a mainly aims to add value for all participants in the economic life. In the organizations, the achievement of the concept of sustainable development is achieved through the concept of societal responsibility of the organizations. For this scope we need to use the term introduced by Elkington namely “The Triple Bottom Line” which involve economic prosperity, environmental compliance and improve social cohesion. [11]. So, “The Triple Bottom Line” can be defined as an approach for measuring the overall performance of an organization according to its triple contribution to the three aspects mentioned above. The new conceptual framework change radically the final aim of a company because it is not anymore maximizing the value of shares held by shareholders, but it is maximizing value for all stakeholders, where shareholders are just another category of stakeholders. Sustainable development and globalization require new performance standards that exceed the economic field, for both national company and international ones. As a consequence, these standards must be integrated into the company's development strategy, to ensure sustainability of activities carried, by the harmonization of economic, social and environmental objectives.

  17. Enhanced expression and activation of pro-inflammatory transcription factors distinguish aneurysmal from atherosclerotic aorta: IL-6- and IL-8-dominated inflammatory responses prevail in the human aneurysm

    NARCIS (Netherlands)

    Lindeman, J.H.N.; Abdul-Hussien, H.; Schaapherder, A.F.M.; Bockel, J.H. van; Thüsen, J.H. vonder; Roelen, D.L.; Kleemann, R.

    2008-01-01

    Inflammation plays a key role in the pathogenesis of an AAA (abdominal aortic aneurysm); however, the nature of the inflammatory factors and cellular response(s) involved in AAA growth is controversial. In the present study, we set out to determine the aortic levels of inflammatory cytokines in

  18. Dural administration of inflammatory soup or Complete Freund's Adjuvant induces activation and inflammatory response in the rat trigeminal ganglion

    DEFF Research Database (Denmark)

    Lukács, M; Haanes, K A; Majláth, Zs

    2015-01-01

    induces inflammatory activation in the trigeminal ganglion. METHODS: We performed topical administration of inflammatory soup (IS) or Complete Freund's Adjuvant (CFA) onto an exposed area of the rat dura mater in vivo for 20 min. The window was closed and the rats were sacrificed after 4 h and up to 7...... days. Myography was performed on middle meningeal arteries. The trigeminal ganglia were removed and processed for immunohistochemistry or Western blot. RESULTS: Both CFA and IS induced enhanced expression of pERK1/2, IL-1β and CGRP in the trigeminal ganglia. The pERK1/2 immunoreactivity was mainly seen...... vasoconstrictor response to IS, but not to CFA. CONCLUSIONS: These results suggest that the application of IS or CFA onto the dura mater causes long-term activation of the TG and demonstrate the importance of the neuro-glial interaction in the activation of the trigeminovascular system....

  19. Sustainable Eco Coastal Development Through Corporate Social Responsibility (CSR) Program

    Science.gov (United States)

    Rakhmanissazly, Arsi; Mursito Ardy, Yong; Abdullah

    2017-02-01

    Besides technical problems the company’s operational constraints that may effect high deficiency for the company is the company - community conflicts. Company - community conflict can also arise depends on the geographic conditions and characteristics of the community itself. Some studies has show that coastal community have higher level of social risk when compared to non-coastal community. Also, the coastal community ussually only rely on what sea provides as their main livelihood. Because of the level of education still contemtible the community couldn’t optimized the potential of their own area. Corporate Social Responsibility (CSR) har emerged as an important approach for addressing the social and environmental impact of company activities. Through CSR program, PT Pertamina EP Asset 3 Tambun Field (PEP) try to form value integration by utilizing resources from the community and the company by making sustainable eco - coastal living in Desa Tambaksari, Karawang, one of PEP working area. Using sustainable livelihood approach begin with compiling data by doing social mapping PEP has initiate the area to becoming Fish Processing Industry Centre. By implementing PDCA in every steps of the program, PEP has multiplied some other programs such as Organic Fish Feed Processing, Seaweed Farming and Waste Bank for Green Coastal Village. These program is PEP’s effort to create a sustainability environment by enhancing the community’s potentials as well as resolving social problems around Tambaksari. The most important result besides getting our license to operate from the community, is the community itself can grow into an eco coastal sustainable system.

  20. Common mechanism in endothelin-3 and PAF receptor function for anti-inflammatory responses.

    Science.gov (United States)

    Sato, Akira; Ebina, Keiichi

    2013-10-15

    Platelet-activating factor (PAF) is a potent lipid mediator that is implicated in numerous inflammatory diseases. Under inflammatory conditions, PAF is biosynthesized through the remodelling pathway and elicits many inflammatory responses through binding to its specific PAF receptor. Endogenous bioactive endothelins (ETs: ET-1, -2, and -3) are also considered potent inflammatory mediators that play a critical role in many inflammatory diseases. In this perspective, we provide a brief overview of possible common mechanisms in ETs and PAF receptor function for inflammatory responses. Accumulating evidence strongly suggests that ET-3, but not ET-1 and ET-2, can attenuate PAF-induced inflammation through direct binding of the Tyr-Lys-Asp (YKD) region in the peptide to PAF and its metabolite/precursor lyso-PAF, followed by inhibition of binding between PAF and its receptor. Additionally, YKD sequence-containing peptides may be useful as a novel type of anti-inflammatory drugs targeting this mechanism. These findings should lead to new treatment strategies for numerous inflammatory diseases by targeting the common mechanism in ET and PAF receptor function. © 2013 Elsevier B.V. All rights reserved.

  1. Attenuating the Systemic Inflammatory Response to Adult Cardiopulmonary Bypass: A Critical Review of the Evidence Base

    Science.gov (United States)

    Landis, R. Clive; Brown, Jeremiah R.; Fitzgerald, David; Likosky, Donald S.; Shore-Lesserson, Linda; Baker, Robert A.; Hammon, John W.

    2014-01-01

    Abstract: A wide range of pharmacological, surgical, and mechanical pump approaches have been studied to attenuate the systemic inflammatory response to cardiopulmonary bypass, yet no systematically based review exists to cover the scope of anti-inflammatory interventions deployed. We therefore conducted an evidence-based review to capture “self-identified” anti-inflammatory interventions among adult cardiopulmonary bypass procedures. To be included, trials had to measure at least one inflammatory mediator and one clinical outcome, specified in the “Outcomes 2010” consensus statement. Ninety-eight papers satisfied inclusion criteria and formed the basis of the review. The review identified 33 different interventions and approaches to attenuate the systemic inflammatory response. However, only a minority of papers (35 of 98 [35.7%]) demonstrated any clinical improvement to one or more of the predefined outcome measures (most frequently myocardial protection or length of intensive care unit stay). No single intervention was supported by strong level A evidence (multiple randomized controlled trials [RCTs] or meta-analysis) for clinical benefit. Interventions at level A evidence included off-pump surgery, minimized circuits, biocompatible circuit coatings, leukocyte filtration, complement C5 inhibition, preoperative aspirin, and corticosteroid prophylaxis. Interventions at level B evidence (single RCT) for minimizing inflammation included nitric oxide donors, C1 esterase inhibition, neutrophil elastase inhibition, propofol, propionyl-L-carnitine, and intensive insulin therapy. A secondary analysis revealed that suppression of at least one inflammatory marker was necessary but not sufficient to confer clinical benefit. The most effective interventions were those that targeted multiple inflammatory pathways. These observations are consistent with a “multiple hit” hypothesis, whereby clinically effective suppression of the systemic inflammatory response

  2. No inflammatory gene-expression response to acute exercise in human Achilles tendinopathy

    DEFF Research Database (Denmark)

    Pingel, Jessica; Fredberg, Ulrich; Mikkelsen, Lone Ramer

    2013-01-01

    Although histology data favour the view of a degenerative nature of tendinopathy, indirect support for inflammatory reactions to loading in affected tendons exists. The purpose of the present study was to elucidate whether inflammatory signalling responses after acute mechanical loading were more....... All ultrasonographic outcomes were unchanged in response to acute exercise and not influenced by NSAID. The signalling for collagen and TGF-beta was upregulated after acute loading in tendinopathic tendon. In contrast to the hypothesis, inflammatory signalling was not exaggerated in tendinopathic...... pronounced in tendinopathic versus healthy regions of human tendon and if treatment with non-steroidal anti-inflammatory medications (NSAID's) reduces this response. Twenty-seven tendinopathy patients (>6 months) were randomly assigned to a placebo (n = 14) or NSAID (Ibumetin NYCOMED GmbH Plant Oranienburg...

  3. Functional Food Targeting the Regulation of Obesity-Induced Inflammatory Responses and Pathologies

    Directory of Open Access Journals (Sweden)

    Shizuka Hirai

    2010-01-01

    Full Text Available Obesity is associated with a low-grade systemic chronic inflammatory state, characterized by the abnormal production of pro- and anti-inflammatory adipocytokines. It has been found that immune cells such as macrophages can infiltrate adipose tissue and are responsible for the majority of inflammatory cytokine production. Obesity-induced inflammation is considered a potential mechanism linking obesity to its related pathologies, such as insulin resistance, cardiovascular diseases, type-2 diabetes, and some immune disorders. Therefore, targeting obesity-related inflammatory components may be a useful strategy to prevent or ameliorate the development of such obesity-related diseases. It has been shown that several food components can modulate inflammatory responses in adipose tissue via various mechanisms, some of which are dependent on peroxisome proliferator-activated receptor γ (PPARγ, whereas others are independent on PPARγ, by attenuating signals of nuclear factor-κB (NF-κB and/or c-Jun amino-terminal kinase (JNK. In this review, we introduce the beneficial effects of anti-inflammatory phytochemicals that can help prevent obesity-induced inflammatory responses and pathologies.

  4. Dismicrobism in inflammatory bowel disease and colorectal cancer: Changes in response of colocytes

    Science.gov (United States)

    Tomasello, Giovanni; Tralongo, Pietro; Damiani, Provvidenza; Sinagra, Emanuele; Di Trapani, Benedetto; Zeenny, Marie Noelle; Hajj Hussein, Inaya; Jurjus, Abdo; Leone, Angelo

    2014-01-01

    influenced by diet and age, as well as genetic factors. Increasing evidence indicates that dysbiosis favors the production of genotoxins and metabolites associated with carcinogenesis and induces dysregulation of the immune response which promotes and sustains inflammation in IBD leading to carcinogenesis. A disequilibrium in gut microflora composition leads to the specific activation of gut associated lymphoid tissue. The associated chronic inflammatory process associated increases the risk of developing CRC. Ulcerative colitis and Crohn’s disease are the two major IBDs characterized by an early onset and extraintestinal manifestations, such as rheumatoid arthritis. The pathogenesis of both diseases is complex and not yet fully known. However, it is widely accepted that an inappropriate immune response to microbial flora can play a pivotal role in IBD pathogenesis. PMID:25561781

  5. Dismicrobism in inflammatory bowel disease and colorectal cancer: changes in response of colocytes.

    Science.gov (United States)

    Tomasello, Giovanni; Tralongo, Pietro; Damiani, Provvidenza; Sinagra, Emanuele; Di Trapani, Benedetto; Zeenny, Marie Noelle; Hussein, Inaya Hajj; Jurjus, Abdo; Leone, Angelo

    2014-12-28

    influenced by diet and age, as well as genetic factors. Increasing evidence indicates that dysbiosis favors the production of genotoxins and metabolites associated with carcinogenesis and induces dysregulation of the immune response which promotes and sustains inflammation in IBD leading to carcinogenesis. A disequilibrium in gut microflora composition leads to the specific activation of gut associated lymphoid tissue. The associated chronic inflammatory process associated increases the risk of developing CRC. Ulcerative colitis and Crohn's disease are the two major IBDs characterized by an early onset and extraintestinal manifestations, such as rheumatoid arthritis. The pathogenesis of both diseases is complex and not yet fully known. However, it is widely accepted that an inappropriate immune response to microbial flora can play a pivotal role in IBD pathogenesis.

  6. Weight cycling enhances adipose tissue inflammatory responses in male mice.

    Directory of Open Access Journals (Sweden)

    Sandra Barbosa-da-Silva

    Full Text Available BACKGROUND: Obesity is associated with low-grade chronic inflammation attributed to dysregulated production, release of cytokines and adipokines and to dysregulated glucose-insulin homeostasis and dyslipidemia. Nutritional interventions such as dieting are often accompanied by repeated bouts of weight loss and regain, a phenomenon known as weight cycling (WC. METHODS: In this work we studied the effects of WC on the feed efficiency, blood lipids, carbohydrate metabolism, adiposity and inflammatory markers in C57BL/6 male mice that WC two or three consecutive times by alternation of a high-fat (HF diet with standard chow (SC. RESULTS: The body mass (BM grew up in each cycle of HF feeding, and decreased after each cycle of SC feeding. The alterations observed in the animals feeding HF diet in the oral glucose tolerance test, in blood lipids, and in serum and adipose tissue expression of adipokines were not recuperated after WC. Moreover, the longer the HF feeding was (two, four and six months, more severe the adiposity was. After three consecutive WC, less marked was the BM reduction during SC feeding, while more severe was the BM increase during HF feeding. CONCLUSION: In conclusion, the results of the present study showed that both the HF diet and WC are relevant to BM evolution and fat pad remodeling in mice, with repercussion in blood lipids, homeostasis of glucose-insulin and adipokine levels. The simple reduction of the BM during a WC is not able to recover the high levels of adipokines in the serum and adipose tissue as well as the pro-inflammatory cytokines enhanced during a cycle of HF diet. These findings are significant because a milieu with altered adipokines in association with WC potentially aggravates the chronic inflammation attributed to dysregulated production and release of adipokines in mice.

  7. Sirt2 suppresses inflammatory responses in collagen-induced arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Jiangtao [Department of Orthopaedics, Qilu Hospital, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong 250012 (China); Department of Orthopaedics, Yantaishan Hospital, 91 Jiefang Road, Yantai, Shandong 264001 (China); Sun, Bing; Jiang, Chuanqiang; Hong, Huanyu [Department of Orthopaedics, Yantaishan Hospital, 91 Jiefang Road, Yantai, Shandong 264001 (China); Zheng, Yanping, E-mail: yanpingzheng@yahoo.com [Department of Orthopaedics, Qilu Hospital, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong 250012 (China)

    2013-11-29

    Highlights: •Sirt2 expression decreases in collagen-induced arthritis (CIA). •Sirt2 knockout aggravates severity of arthritis in mice with CIA. •Sirt2 knockout increases levels of pro-inflammatory factors in the serum. •Sirt2 deacetylates p65 and inhibits pro-inflammatory factors expression. •Sirt2 rescue abates severity of arthritis in mice with CIA. -- Abstract: Arthritis is a common autoimmune disease that is associated with progressive disability, systemic complications and early death. However, the underling mechanisms of arthritis are still unclear. Sirtuins are a NAD{sup +}-dependent class III deacetylase family, and regulate cellular stress, inflammation, genomic stability, carcinogenesis, and energy metabolism. Among the sirtuin family members, Sirt1 and Sirt6 are critically involved in the development of arthritis. It remains unknown whether other sirtuin family members participate in arthritis. Here in this study, we demonstrate that Sirt2 inhibits collagen-induced arthritis (CIA) using in vivo and in vitro evidence. The protein and mRNA levels of Sirt2 significantly decreased in joint tissues of mice with CIA. When immunized with collagen, Sirt2-KO mice showed aggravated severity of arthritis based on clinical scores, hind paw thickness, and radiological and molecular findings. Mechanically, Sirt2 deacetylated p65 subunit of nuclear factor-kappa B (NF-κB) at lysine 310, resulting in reduced expression of NF-κB-dependent genes, including interleukin 1β (IL-1β), IL-6, monocyte chemoattractant protein 1(MCP-1), RANTES, matrix metalloproteinase 9 (MMP-9) and MMP-13. Importantly, our rescue experiment showed that Sirt2 re-expression abated the severity of arthritis in Sirt2-KO mice. Those findings strongly indicate Sirt2 as a considerably inhibitor of the development of arthritis.

  8. The laminin response in inflammatory bowel disease: protection or malignancy?

    Directory of Open Access Journals (Sweden)

    Caroline Spenlé

    Full Text Available Laminins (LM, basement membrane molecules and mediators of epithelial-stromal communication, are crucial in tissue homeostasis. Inflammatory Bowel Diseases (IBD are multifactorial pathologies where the microenvironment and in particular LM play an important yet poorly understood role in tissue maintenance, and in cancer progression which represents an inherent risk of IBD. Here we showed first that in human IBD colonic samples and in murine colitis the LMα1 and LMα5 chains are specifically and ectopically overexpressed with a concomitant nuclear p53 accumulation. Linked to this observation, we provided a mechanism showing that p53 induces LMα1 expression at the promoter level by ChIP analysis and this was confirmed by knockdown in cell transfection experiments. To mimic the human disease, we induced colitis and colitis-associated cancer by chemical treatment (DSS combined or not with a carcinogen (AOM in transgenic mice overexpressing LMα1 or LMα5 specifically in the intestine. We demonstrated that high LMα1 or LMα5 expression decreased susceptibility towards experimentally DSS-induced colon inflammation as assessed by histological scoring and decrease of pro-inflammatory cytokines. Yet in a pro-oncogenic context, we showed that LM would favor tumorigenesis as revealed by enhanced tumor lesion formation in both LM transgenic mice. Altogether, our results showed that nuclear p53 and associated overexpression of LMα1 and LMα5 protect tissue from inflammation. But in a mutation setting, the same LM molecules favor progression of IBD into colitis-associated cancer. Our transgenic mice represent attractive new models to acquire knowledge about the paradoxical effect of LM that mediate either tissue reparation or cancer according to the microenvironment. In the early phases of IBD, reinforcing basement membrane stability/organization could be a promising therapeutic approach.

  9. Bee Venom Decreases LPS-Induced Inflammatory Responses in Bovine Mammary Epithelial Cells.

    Science.gov (United States)

    Jeong, Chang Hee; Cheng, Wei Nee; Bae, Hyojin; Lee, Kyung Woo; Han, Sang Mi; Petriello, Michael C; Lee, Hong Gu; Seo, Han Geuk; Han, Sung Gu

    2017-10-28

    The world dairy industry has long been challenged by bovine mastitis, an inflammatory disease, which causes economic loss due to decreased milk production and quality. Attempts have been made to prevent or treat this disease with multiple approaches, primarily through increased abuse of antibiotics, but effective natural solutions remain elusive. Bee venom (BV) contains a variety of peptides (e.g., melittin) and shows multiple bioactivities, including prevention of inflammation. Thus, in the current study, it was hypothesized that BV can reduce inflammation in bovine mammary epithelial cells (MAC-T). To examine the hypothesis, cells were treated with LPS (1 μg/ml) to induce an inflammatory response and the anti-inflammatory effects of BV (2.5 and 5 μg/ml) were investigated. The cellular mechanisms of BV against LPS-induced inflammation were also investigated. Results showed that BV can attenuate expression of an inflammatory protein, COX2, and pro-inflammatory cytokines such as IL-6 and TNF-α. Activation of NF-κB, an inflammatory transcription factor, was significantly downregulated by BV in cells treated with LPS, through dephosphorylation of ERK1/2. Moreover, pretreatment of cells with BV attenuated LPS-induced production of intracellular reactive oxygen species (e.g., superoxide anion). These results support our hypothesis that BV can decrease LPS-induced inflammatory responses in bovine mammary epithelial cells through inhibition of oxidative stress, NF-κB, ERK1/2, and COX-2 signaling.

  10. African Trypanosomes Undermine Humoral Responses and Vaccine Development: Link with Inflammatory Responses?

    Directory of Open Access Journals (Sweden)

    Benoit Stijlemans

    2017-05-01

    Full Text Available African trypanosomosis is a debilitating disease of great medical and socioeconomical importance. It is caused by strictly extracellular protozoan parasites capable of infecting all vertebrate classes including human, livestock, and game animals. To survive within their mammalian host, trypanosomes have evolved efficient immune escape mechanisms and manipulate the entire host immune response, including the humoral response. This report provides an overview of how trypanosomes initially trigger and subsequently undermine the development of an effective host antibody response. Indeed, results available to date obtained in both natural and experimental infection models show that trypanosomes impair homeostatic B-cell lymphopoiesis, B-cell maturation and survival and B-cell memory development. Data on B-cell dysfunctioning in correlation with parasite virulence and trypanosome-mediated inflammation will be discussed, as well as the impact of trypanosomosis on heterologous vaccine efficacy and diagnosis. Therefore, new strategies aiming at enhancing vaccination efficacy could benefit from a combination of (i early parasite diagnosis, (ii anti-trypanosome (drugs treatment, and (iii anti-inflammatory treatment that collectively might allow B-cell recovery and improve vaccination.

  11. Allelic Variation on Murine Chromosome 11 Modifies Host Inflammatory Responses and Resistance to Bacillus anthracis

    Science.gov (United States)

    2011-12-01

    stimuli [53–56]. Indeed, Arrb2 regulates LPS- induced inflammatory response and endotoxemia [54,55], while Ntn1 can minimize inflammatory damage ...MyD88-dependent signaling protects against anthrax lethal toxin-induced impairment of intestinal barrier function. Infect Immun 79: 118–124. 39. Henry T...Olien L, Gauthier S, Skamene E, Morgan K, et al. (1998) Mapping of genetic modulators of natural resistance to infection with Salmonella typhimurium

  12. Development of a macromolecular prodrug for the treatment of inflammatory arthritis: mechanisms involved in arthrotropism and sustained therapeutic efficacy

    Science.gov (United States)

    2010-01-01

    Introduction The purpose of the present manuscript is to test the hypothesis that arthrotropic localization and synovial cell internalization account for the unique capacity of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-dexamethasone conjugate (P-Dex, a macromolecular prodrug of dexamethasone) to induce sustained amelioration of joint inflammation and inhibition of tissue damage in an animal model of inflammatory arthritis. Methods Rats with adjuvant-induced arthritis (AA) were treated with P-Dex, free dexamethasone, saline or HPMA homopolymer. To define the biodistribution of P-Dex, conjugates with different imaging labels were given to AA rats and analyzed. Isolated joint tissues were evaluated by fluorescence-activated cell sorting (FACS) and immunohistochemical staining. Cellular uptake of P-Dex and its effects on apoptosis and production of proinflammatory cytokines were examined using human monocyte-macrophages and fibroblasts. Results A single systemic administration of P-Dex completely suppressed AA for >20 days. Magnetic resonance imaging demonstrated higher HPMA copolymer influx into the inflamed joints than the normal joints. Immunohistochemistry and FACS analyses of arthritic joints revealed extensive uptake of the polymer conjugate by synovial fibroblasts and myeloid lineage cells. The capacity of P-Dex to suppress inflammation was confirmed in monocyte-macrophage cultures in which P-Dex treatment resulted in suppression of lipopolysaccharide-induced IL-6 and TNFα release. Similarly, TNFα-induced expression of matrix metalloproteinases (MMP1 and MMP3) in synovial fibroblasts from a rheumatoid arthritis patient was suppressed by P-Dex. P-Dex showed no detectable effect on monocyte apoptosis. Conclusions P-Dex provides superior and sustained amelioration of AA compared with an equivalent dose of free dexamethasone. The arthrotropism and local retention of P-Dex is attributed to the enhanced vascular permeability in arthritic joints and the

  13. Impact of corporate social responsibility on sustainable enterprise development

    Directory of Open Access Journals (Sweden)

    Danubianu Mirela

    2017-06-01

    Top management endorsement and nomination of a complex CSR teamDeveloping formal company CSR policy documentsSelecting and engaging the company’s stakeholders as early as possible.Building a Project Advisory Board – useful in every modern managerial tool application should guide the progress toward CSR.An external facilitator would help solve internal conflicts.An audit of what CSR represents for the Company, what are the CSR options, e.g., promoting a “green company” profile, what would be the best impact of philanthropy and community volunteering, etc.Generate a CSR portfolio of actions, setting deadlines, responsibilities and allocating resources, establishing communication, reporting, monitoring and corrective proceduresupgrading the sustainable enterprise strategy.

  14. Isoliquiritigenin protects against sepsis-induced lung and liver injury by reducing inflammatory responses.

    Science.gov (United States)

    Chen, Xiong; Cai, Xueding; Le, Rongrong; Zhang, Man; Gu, Xuemei; Shen, Feixia; Hong, Guangliang; Chen, Zimiao

    2018-02-05

    Sepsis, one of the most fatal diseases worldwide, often leads to multiple organ failure, mainly due to uncontrolled inflammatory responses. Despite accumulating knowledge obtained in recent years, effective drugs to treat sepsis in the clinic are still urgently needed. Isoliquiritigenin (ISL), a chalcone compound, has been reported to exert anti-inflammatory properties. However, little is known about the effects of ISL on sepsis and its related complications. In this study, we investigated the potential protective effects of ISL on lipopolysaccharide (LPS)-induced injuries and identified the mechanisms underlying these effects. ISL inhibited inflammatory cytokine expression in mouse primary peritoneal macrophages (MPMs) exposed to LPS. In an acute lung injury (ALI) mouse model, ISL prevented LPS-induced structural damage and inflammatory cell infiltration. Additionally, pretreatment with ISL attenuated sepsis-induced lung and liver injury, accompanied by a reduction in inflammatory responses. Moreover, these protective effects were mediated by the nuclear factor kappa B (NF-κB) pathway-mediated inhibition of inflammatory responses in vitro and in vivo. Our study suggests that ISL may be a potential therapeutic agent for sepsis-induced injuries. Copyright © 2017. Published by Elsevier Inc.

  15. Proteomics profiling reveals inflammatory biomarkers of antidepressant treatment response: Findings from the CO-MED trial.

    Science.gov (United States)

    Gadad, Bharathi S; Jha, Manish K; Grannemann, Bruce D; Mayes, Taryn L; Trivedi, Madhukar H

    2017-11-01

    Animal and human studies suggest an association between depression and aberrant immune response. Further, common inflammatory markers may change during the course of antidepressant treatment in patients. The objective of this study was to evaluate changes in inflammatory markers and clinical outcomes from subjects enrolled in the Combining Medications to Enhance Depression Outcome (CO-MED) trial. At baseline and week 12 (treatment completion), plasma samples of 102 participants were analyzed via a multiplex assay comprised of inflammatory markers using a 27-plex standard assay panel plus a 4-plex human acute phase xMAP technology based platform. We carried out analyses in two steps. First, t-tests were used to identify inflammatory marker levels that changed between baseline and week 12. For markers that were altered, logistic regression models were then conducted to look for associated changes in remission at week 12. Among the 31 inflammatory markers analyzed, several cytokines (IL-5, IFN-γ, IL-13), two chemokines (Eotaxin-1/CCL11, RANTES) and an acute-phase reactant (serum amyloid P component) showed change from baseline to week 12. However, only two indicated differential remission responses. Interestingly, increased levels of Eotaxin-1/CCL11 correlated with remission at week 12, whereas decreased levels of IFN-γ correlated with non-remission at week 12. Results suggest that these inflammatory proteins may serve as predictors of treatment response. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Myeloid Heme Oxygenase-1 Regulates the Acute Inflammatory Response to Zymosan in the Mouse Air Pouch

    Directory of Open Access Journals (Sweden)

    Rita Brines

    2018-01-01

    Full Text Available Heme oxygenase-1 (HO-1 is induced by many stimuli to modulate the activation and function of different cell types during innate immune responses. Although HO-1 has shown anti-inflammatory effects in different systems, there are few data on the contribution of myeloid HO-1 and its role in inflammatory processes is not well understood. To address this point, we have used HO-1M-KO mice with myeloid-restricted deletion of HO-1 to specifically investigate its influence on the acute inflammatory response to zymosan in vivo. In the mouse air pouch model, we have shown an exacerbated inflammation in HO-1M-KO mice with increased neutrophil infiltration accompanied by high levels of inflammatory mediators such as interleukin-1β, tumor necrosis factor-α, and prostaglandin E2. The expression of the degradative enzyme matrix metalloproteinase-3 (MMP-3 was also enhanced. In addition, we observed higher levels of serum MMP-3 in HO-1M-KO mice compared with control mice, suggesting the presence of systemic inflammation. Altogether, these findings demonstrate that myeloid HO-1 plays an anti-inflammatory role in the acute response to zymosan in vivo and suggest the interest of this target to regulate inflammatory processes.

  17. Interleukin 37 expression in mice alters sleep responses to inflammatory agents and influenza virus infection

    NARCIS (Netherlands)

    Davis, C.J.; Zielinski, M.R.; Dunbrasky, D.; Taishi, P.; Dinarello, C.A.; Krueger, J.M.

    2017-01-01

    Multiple interactions between the immune system and sleep are known, including the effects of microbial challenge on sleep or the effects of sleep loss on facets of the immune response. Cytokines regulate, in part, sleep and immune responses. Here we examine the role of an anti-inflammatory

  18. Rosmarinus officinalis Extract Suppresses Propionibacterium acnes–Induced Inflammatory Responses

    Science.gov (United States)

    Tsai, Tsung-Hsien; Chuang, Lu-Te; Lien, Tsung-Jung; Liing, Yau-Rong; Chen, Wei-Yu

    2013-01-01

    Abstract Propionibacterium acnes is a key pathogen involved in the progression of acne inflammation. The development of a new agent possessing antimicrobial and anti-inflammatory activity against P. acnes is therefore of interest. In this study, we investigated the inhibitory effect of rosemary (Rosmarinus officinalis) extract on P. acnes–induced inflammation in vitro and in vivo. The results showed that ethanolic rosemary extract (ERE) significantly suppressed the secretion and mRNA expression of proinflammatory cytokines, including interleukin (IL)-8, IL-1β, and tumor necrosis factor-α in P. acnes–stimulated monocytic THP-1 cells. In an in vivo mouse model, concomitant intradermal injection of ERE attenuated the P. acnes–induced ear swelling and granulomatous inflammation. Since ERE suppressed the P. acnes–induced nuclear factor kappa-B (NF-κB) activation and mRNA expression of Toll-like receptor (TLR) 2, the suppressive effect of ERE might be due, at least partially, to diminished NF-κB activation and TLR2-mediated signaling pathways. Furthermore, three major constituents of ERE, carnosol, carnosic acid, and rosmarinic acid, exerted different immumodulatory activities in vitro. In brief, rosmarinic acid significantly suppressed IL-8 production, while the other two compounds inhibited IL-1β production. Further study is needed to explore the role of bioactive compounds of rosemary in mitigation of P. acnes–induced inflammation. PMID:23514231

  19. Soluble Mediators in Platelet Concentrates Modulate Dendritic Cell Inflammatory Responses in an Experimental Model of Transfusion.

    Science.gov (United States)

    Perros, Alexis J; Christensen, Anne-Marie; Flower, Robert L; Dean, Melinda M

    2015-10-01

    The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such as soluble CD40 ligand (sCD40L), RANTES, and interleukin (IL)-8. An in vitro whole blood culture transfusion model was employed to assess whether mediators present in PC supernatants (PC-SNs) modulated dendritic cell (DC)-specific inflammatory responses (intracellular staining) and the overall inflammatory response (cytometric bead array). Lipopolysaccharide (LPS) was included in parallel cultures to model the impact of PC-SNs on cell responses following toll-like receptor-mediated pathogen recognition. The impact of both the PC dose (10%, 25%) and ex vivo storage period was investigated [day 2 (D2), day 5 (D5), day 7 (D7)]. PC-SNs alone had minimal impact on DC-specific inflammatory responses and the overall inflammatory response. However, in the presence of LPS, exposure to PC-SNs resulted in a significant dose-associated suppression of the production of DC IL-12, IL-6, IL-1α, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein (MIP)-1β and storage-associated suppression of the production of DC IL-10, TNF-α, and IL-8. For the overall inflammatory response, IL-6, TNF-α, MIP-1α, MIP-1β, and inflammatory protein (IP)-10 were significantly suppressed and IL-8, IL-10, and IL-1β significantly increased following exposure to PC-SNs in the presence of LPS. These data suggest that soluble mediators present in PCs significantly suppress DC function and modulate the overall inflammatory response, particularly in the presence of an infectious stimulus. Given the central role of DCs in the initiation and regulation of the immune response, these results suggest that modulation of the DC inflammatory profile is a probable mechanism contributing to transfusion-related complications.

  20. Wound trauma mediated inflammatory signaling attenuates a tissue regenerative response in MRL/MpJ mice

    Directory of Open Access Journals (Sweden)

    Elster Eric A

    2010-05-01

    Full Text Available Abstract Background Severe trauma can induce pathophysiological responses that have marked inflammatory components. The development of systemic inflammation following severe thermal injury has been implicated in immune dysfunction, delayed wound healing, multi-system organ failure and increased mortality. Methods In this study, we examined the impact of thermal injury-induced systemic inflammation on the healing response of a secondary wound in the MRL/MpJ mouse model, which was anatomically remote from the primary site of trauma, a wound that typically undergoes scarless healing in this specific strain. Ear-hole wounds in MRL/MpJ mice have previously displayed accelerated healing and tissue regeneration in the absence of a secondary insult. Results Severe thermal injury in addition to distal ear-hole wounds induced marked local and systemic inflammatory responses in the lungs and significantly augmented the expression of inflammatory mediators in the ear tissue. By day 14, 61% of the ear-hole wounds from thermally injured mice demonstrated extensive inflammation with marked inflammatory cell infiltration, extensive ulceration, and various level of necrosis to the point where a large percentage (38% had to be euthanized early during the study due to extensive necrosis, inflammation and ear deformation. By day 35, ear-hole wounds in mice not subjected to thermal injury were completely closed, while the ear-hole wounds in thermally injured mice exhibited less inflammation and necrosis and only closed partially (62%. Thermal injury resulted in marked increases in serum levels of IL-6, TNFα, KC (CXCL1, and MIP-2α (CXCL2. Interestingly, attenuated early ear wound healing in the thermally injured mouse resulted in incomplete tissue regeneration in addition to a marked inflammatory response, as evidenced by the histological appearance of the wound and increased transcription of potent inflammatory mediators. Conclusion These findings suggest that the

  1. An Unbalanced Inflammatory Cytokine Response Is Not Associated With Mortality Following Sepsis: A Prospective Cohort Study.

    Science.gov (United States)

    Frencken, Jos F; van Vught, Lonneke A; Peelen, Linda M; Ong, David S Y; Klein Klouwenberg, Peter M C; Horn, Janneke; Bonten, Marc J M; van der Poll, Tom; Cremer, Olaf L

    2017-05-01

    The prevailing theory of host response during sepsis states that an excessive production of pro-inflammatory mediators causes early deaths, whereas a predominantly anti-inflammatory response may lead to immunosuppression, secondary infection, and late deaths. We assessed inflammatory (im)balance by measuring pro-inflammatory interleukin-6 and anti-inflammatory interleukin-10 during three distinct time periods after sepsis, and assessed its association with mortality. Prospective observational cohort. Two tertiary mixed ICUs in The Netherlands. Consecutive patients presenting with severe sepsis or septic shock from 2011 to 2013. None. We repeatedly measured plasma interleukin-6 and interleukin-10 concentrations using cytometric bead array. Poisson regression was used to analyze the relation between inflammatory markers measured on 1) ICU admission and day 4 mortality, 2) day 4 and day 28 mortality, and 3) ICU discharge and 1-year mortality. Secondary outcome was development of ICU-acquired infections. Among 708 patients, 86 (12%) died within 4 days, 140 (20%) died between days 4 and 28, and an additional 155 (22%) died before 1 year. Interleukin-6 and interleukin-10 levels were both independently associated with mortality, but the balance of this response as modelled by an interleukin-6 and interleukin-10 interaction term was not (relative risk, 0.99; 95% CI, 0.95-1.04 on admission; relative risk, 1.02; 95% CI, 0.98-1.06 on day 4; and relative risk, 1.12; 95% CI, 0.98-1.29 at ICU discharge). However, inflammatory imbalance on day 4 was associated with development of ICU-acquired infections (subdistribution hazard ratio, 0.87; 95% CI, 0.77-0.98). Although both interleukin-6 and interleukin-10 productions are associated with death, the balance of these inflammatory mediators does not seem to impact either early, intermediate, or late mortality in patients presenting to the ICU with sepsis.

  2. Host Transcription Factors in the Immediate Pro-Inflammatory Response to the Parasitic Mite Psoroptes ovis

    Science.gov (United States)

    Burgess, Stewart T. G.; McNeilly, Tom N.; Watkins, Craig A.; Nisbet, Alasdair J.; Huntley, John F.

    2011-01-01

    Background Sheep scab, caused by infestation with the ectoparasitic mite Psoroptes ovis, results in the rapid development of cutaneous inflammation and leads to the crusted skin lesions characteristic of the disease. We described previously the global host transcriptional response to infestation with P. ovis, elucidating elements of the inflammatory processes which lead to the development of a rapid and profound immune response. However, the mechanisms by which this response is instigated remain unclear. To identify novel methods of intervention a better understanding of the early events involved in triggering the immune response is essential. The objective of this study was to gain a clearer understanding of the mechanisms and signaling pathways involved in the instigation of the immediate pro-inflammatory response. Results Through a combination of transcription factor binding site enrichment and pathway analysis we identified key roles for a number of transcription factors in the instigation of cutaneous inflammation. In particular, defined roles were elucidated for the transcription factors NF-kB and AP-1 in the orchestration of the early pro-inflammatory response, with these factors being implicated in the activation of a suite of inflammatory mediators. Conclusions Interrogation of the host temporal response to P. ovis infestation has enabled the further identification of the mechanisms underlying the development of the immediate host pro-inflammatory response. This response involves key regulatory roles for the transcription factors NF-kB and AP-1. Pathway analysis demonstrated that the activation of these transcription factors may be triggered following a host LPS-type response, potentially involving TLR4-signalling and also lead to the intriguing possibility that this could be triggered by a P. ovis allergen. PMID:21915322

  3. Host transcription factors in the immediate pro-inflammatory response to the parasitic mite Psoroptes ovis.

    Directory of Open Access Journals (Sweden)

    Stewart T G Burgess

    Full Text Available BACKGROUND: Sheep scab, caused by infestation with the ectoparasitic mite Psoroptes ovis, results in the rapid development of cutaneous inflammation and leads to the crusted skin lesions characteristic of the disease. We described previously the global host transcriptional response to infestation with P. ovis, elucidating elements of the inflammatory processes which lead to the development of a rapid and profound immune response. However, the mechanisms by which this response is instigated remain unclear. To identify novel methods of intervention a better understanding of the early events involved in triggering the immune response is essential. The objective of this study was to gain a clearer understanding of the mechanisms and signaling pathways involved in the instigation of the immediate pro-inflammatory response. RESULTS: Through a combination of transcription factor binding site enrichment and pathway analysis we identified key roles for a number of transcription factors in the instigation of cutaneous inflammation. In particular, defined roles were elucidated for the transcription factors NF-kB and AP-1 in the orchestration of the early pro-inflammatory response, with these factors being implicated in the activation of a suite of inflammatory mediators. CONCLUSIONS: Interrogation of the host temporal response to P. ovis infestation has enabled the further identification of the mechanisms underlying the development of the immediate host pro-inflammatory response. This response involves key regulatory roles for the transcription factors NF-kB and AP-1. Pathway analysis demonstrated that the activation of these transcription factors may be triggered following a host LPS-type response, potentially involving TLR4-signalling and also lead to the intriguing possibility that this could be triggered by a P. ovis allergen.

  4. Systemic inflammatory response syndrome increases immobility-induced neuromuscular weakness.

    Science.gov (United States)

    Fink, Heidrun; Helming, Marc; Unterbuchner, Christoph; Lenz, Andrea; Neff, Frauke; Martyn, J A Jeevendra; Blobner, Manfred

    2008-03-01

    Inflammation and immobility are comorbid etiological factors inducing muscle weakness in critically ill patients. This study establishes a rat model to examine the effect of inflammation and immobilization alone and in combination on muscle contraction, histology, and acetylcholine receptor regulation. Prospective, randomized, experimental study. Animal laboratory of a university hospital. Sprague-Dawley rats. To produce systemic inflammation, rats (n = 34) received three consecutive intravenous injections of Corynebacterium parvum on days 0, 4, and 8. Control rats (n = 21) received saline. Both groups were further divided to have one hind limb either immobilized by pinning of knee and ankle joints or sham-immobilized (surgical leg). The contralateral nonsurgical leg of each animal served as control (nonsurgical leg). After 12 days, body weight and muscle mass were significantly reduced in all C. parvum animals compared with saline-injected rats. Immobilization led to local muscle atrophy. Normalized to muscle mass, tetanic contraction was reduced in the surgical leg after immobilization (7.64 +/- 1.91 N/g) and after inflammation (8.71 +/- 2.0 N/g; both p immobilization and saline injection, 11.03 +/- 2.26 N/g). Histology showed an increase in inflammatory cells in all C. parvum-injected animals. Immobilization in combination with C. parvum injection had an additive effect on inflammation. Acetylcholine receptors were increased in immobilized muscles and in all muscles of C. parvum-injected animals. The muscle weakness in critically ill patients can be replicated in our novel rat model. Inflammation and immobilization independently lead to muscle weakness.

  5. Amniotic fluid protein profiles of intraamniotic inflammatory response to Ureaplasma spp. and other bacteria.

    Directory of Open Access Journals (Sweden)

    Marian Kacerovsky

    Full Text Available OBJECTIVE: This study aimed to evaluate the amniotic fluid protein profiles and the intensity of intraamniotic inflammatory response to Ureaplasma spp. and other bacteria, using the multiplex xMAP technology. METHODS: A retrospective cohort study was undertaken in the Department of Obstetrics and Gynecology, University Hospital Hradec Kralove, Czech Republic. A total of 145 pregnant women with preterm prelabor rupture of membranes between gestational age 24+0 and 36+6 weeks were included in the study. Amniocenteses were performed. The presence of Ureaplasma spp. and other bacteria was evaluated using 16S rRNA gene sequencing. The levels of specific proteins were determined using multiplex xMAP technology. RESULTS: The presence of Ureaplasma spp. and other bacteria in the amniotic fluid was associated with increased levels of interleukin (IL-6, IL-8, IL-10, brain-derived neurotropic factor, granulocyte macrophage colony stimulating factor, monocyte chemotactic protein-1, macrophage inflammatory protein-1, and matrix metalloproteinasis-9. Ureaplasma spp. were also associated with increased levels of neurotropin-3 and triggering receptor expressed on myeloid cells-1. CONCLUSIONS: The presence of Ureaplasma spp. in the amniotic fluid is associated with a slightly different protein profile of inflammatory response, but the intensity of inflammatory response to Ureaplasma spp. is comparable with the inflammatory response to other bacteria.

  6. The inflammatory response triggered by Influenza virus: a two edged sword.

    Science.gov (United States)

    Tavares, Luciana P; Teixeira, Mauro M; Garcia, Cristiana C

    2017-04-01

    Influenza A virus (IAV) is a relevant respiratory tract pathogen leading to a great number of deaths and hospitalizations worldwide. Secondary bacterial infections are a very common cause of IAV associated morbidity and mortality. The robust inflammatory response that follows infection is important for the control of virus proliferation but is also associated with lung damage, morbidity and death. The role of the different components of immune response underlying protection or disease during IAV infection is not completely elucidated. Overall, in the context of IAV infection, inflammation is a 'double edge sword' necessary to control infection but causing disease. Therefore, a growing number of studies suggest that immunomodulatory strategies may improve disease outcome without affecting the ability of the host to deal with infection. This review summarizes recent aspects of the inflammatory responses triggered by IAV that are preferentially involved in causing severe pulmonary disease and the anti-inflammatory strategies that have been suggested to treat influenza induced immunopathology.

  7. Gut response induced by weaning in piglet features marked changes in immune and inflammatory response.

    Science.gov (United States)

    Bomba, Lorenzo; Minuti, Andrea; Moisá, Sonia J; Trevisi, Erminio; Eufemi, Elisa; Lizier, Michela; Chegdani, Fatima; Lucchini, Franco; Rzepus, Marcin; Prandini, Aldo; Rossi, Filippo; Mazza, Raffaele; Bertoni, Giuseppe; Loor, Juan J; Ajmone-Marsan, Paolo

    2014-12-01

    At weaning, piglets are exposed to many stressors, such as separation from the sow, mixing with other litters, end of lactational immunity, and a change in their environment and gut microbiota. The sudden change of feeding regime after weaning causes morphological and histological changes in the small intestine which are critical for the immature digestive system. Sixteen female piglets were studied to assess the effect of sorbic acid supplementation on the small intestine tissue transcriptome. At weaning day (T0, piglet age 28 days), four piglets were sacrificed and ileal tissue samples collected. The remaining 12 piglets were weighed and randomly assigned to different postweaning (T5, piglet age 33 days) diets. Diet A (n = 6) contained 5 g/kg of sorbic acid. In diet B (n = 6), the organic acids were replaced by barley flour. Total RNA was isolated and then hybridized to CombiMatrix CustomArray™ 90-K platform microarrays, screening about 30 K genes. Even though diet had no detectable effect on the transcriptome during the first 5 days after weaning, results highlighted some of the response mechanisms to the stress of weaning occurring in the piglet gut. A total of 205 differentially expressed genes were used for functional analysis using the bioinformatics tools BLAST2GO, Ingenuity Pathway Analysis 8.0, and Dynamic Impact Approach (DIA). Bioinformatic analysis revealed that apoptosis, RIG-I-like, and NOD-like receptor signaling were altered as a result of weaning. Interferons and caspases gene families were the most activated after weaning in response to piglets to multiple stressors. Results suggest that immune and inflammatory responses were activated and likely are a cause of small intestine atrophy as revealed by a decrease in villus height and villus/crypt ratio.

  8. Sustainable palm oil as a public responsibility? : On the governance capacity of Indonesian standard for sustainable palm oil (ISPO)

    NARCIS (Netherlands)

    Hidayat, Nia; Offermans, Astrid; Glasbergen, Pieter

    2017-01-01

    This paper is motivated by the observation that Southern governments start to take responsibility for a more sustainable production of agricultural commodities as a response to earlier private initiatives by businesses and non-governmental organizations (NGOs). Indonesia is one of the leading

  9. The Systemic Inflammatory Response Syndrome (SIRS) in acutely hospitalised medical patients: a cohort study

    DEFF Research Database (Denmark)

    Comstedt, Pal; Storgaard, Merete; Lassen, Annmarie T

    2009-01-01

    ABSTRACT: BACKGROUND: Sepsis is an infection which has evoked a systemic inflammatory response. Clinically, the Systemic Inflammatory Response Syndrome (SIRS) is identified by two or more symptoms including fever or hypothermia, tachycardia, tachypnoea and change in blood leucocyte count....... The relationship between SIRS symptoms and morbidity and mortality in medical emergency ward patients is unknown. METHODS: We conducted a prospective cohort study of the frequency of SIRS and its relationship to sepsis and death among acutely hospitalised medical patients. In 437 consecutive patients, SIRS status...

  10. Strongly compromised inflammatory response to brain injury in interleukin-6-deficient mice

    DEFF Research Database (Denmark)

    Penkowa, M; Moos, T; Carrasco, J

    1999-01-01

    Injury to the central nervous system (CNS) elicits an inflammatory response involving activation of microglia, brain macrophages, and astrocytes, processes likely mediated by the release of proinflammatory cytokines. In order to determine the role of interleukin-6 (IL-6) during the inflammatory...... response in the brain following disruption of the blood-brain barrier (BBB), we examined the effects of a focal cryo injury to the fronto-parietal cortex in interleukin-6-deficient (IL-6-/-) and normal (IL-6+/+) mice. In IL-6+/+ mice, brain injury resulted in the appearance of brain macrophages...

  11. ASSESSMENT OF INFLAMMATORY RESPONSE INDICATORS AND PERIPHERAL HEMOPOIESIS AT NON-SPECIFIC ULCERATIVE COLITIS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    V. V. Botvinyeva

    2013-01-01

    Full Text Available The article presents the analysis of laboratory tests, which indicate the response of the body to systemic inflammation. The revealed interconnection of these parameters with peripheral hematosis alterations at chronic inflammatory diseases will allow objectively approaching the diagnostics of functional disorders at non-specific ulcerative colitis in children. The authors attempted to develop new approaches to the analysis of laboratory indicators, which will help to evaluate individual dynamics of processes at the systemic inflammatory response of the body and select adequate therapy of the primary disease.

  12. Sustainability as an object of corporate social responsibility

    Directory of Open Access Journals (Sweden)

    Jesús Marí Farinós

    2017-06-01

    Full Text Available We can observe that in the last few years companies and organizations of any nature have begun to show an increasing interest in establishing sustainable relationships with the environment by bridging those groups that are impacted or that impact on their activities, . In this context, the social responsibility report emerges as a management tool that allows companies to be accountable to society and its groups and measure, their environmental, financial and social actions. The Triple Bottom Line, triple accountability or triple counting of results, should be understood as the methodology to measure and report the performance of organizations contrasted with environmental, economic and social parameters. In addition, it allows companies to surpass accountability solely for their economic value as it used to be in the past, and also to consider the social and environmental value they add or destroy. Concern about these social and environmental issues generates a demand for information, which, in turn, leads to the need to have a document that collects the information demanded by society and that should be offered by the Companies, what is known as Social Responsibility. It is the American companies that originally, already in the late sixties and early seventies, found themselves in need of having to offer information regarding their social responsibility. This information was collected in what, we might conclude, is the first social balances, which were addressed mainly to groups outside the company itself, especially to consumers, since in the United States it was this collective that showed a greater concern about the issue.

  13. Effect of Human Amnion Epithelial Cells on the Acute Inflammatory Response in Fetal Sheep

    Directory of Open Access Journals (Sweden)

    Alana Westover

    2017-11-01

    Full Text Available Intra-amniotic (IA lipopolysaccharide (LPS injection in sheep induces inflammation in the fetus. Human amnion epithelial cells (hAECs moderate the effect of IA LPS on fetal development, but their influence on the acute inflammatory response to IA LPS is unknown. We aimed to determine the effects of hAECs on the acute fetal inflammatory response to IA LPS. After surgical instrumentation at 116 days' gestation (d ewes were randomized to 1 of 4 groups at 123 d: IA LPS (10 mg and intravenous (IV saline (n = 8, IA LPS and IV hAECs (n = 6, IA saline and IV saline (n = 5 or IA saline and IV hAECs (n = 5. IV injections were administered immediately after IA injections. Serial fetal blood samples were collected. At 125 d, placental, fetal lung and liver samples were collected. IA LPS increased inflammatory cell recruitment in the placenta and lungs, increased IL-1β and IL-8 mRNA levels in the lungs and increased serum amyloid A3 (SAA3 and C-reactive protein (CRP mRNA levels in the liver. IV hAECs reduced fetal lung inflammatory cell recruitment but did not otherwise alter indices of placental, fetal lung or liver inflammation. The acute fetal inflammatory response to IA LPS is not substantially altered by IV hAEC treatment.

  14. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43

    Science.gov (United States)

    Maslowski, Kendle M.; Vieira, Angelica T.; Ng, Aylwin; Kranich, Jan; Sierro, Frederic; Yu, Di; Schilter, Heidi C.; Rolph, Michael S.; Mackay, Fabienne; Artis, David; Xavier, Ramnik J.; Teixeira, Mauro M.; Mackay, Charles R.

    2011-01-01

    The immune system responds to pathogens by a variety of pattern recognition molecules such as the Toll-like receptors (TLRs), which promote recognition of dangerous foreign pathogens. However, recent evidence indicates that normal intestinal microbiota might also positively influence immune responses, and protect against the development of inflammatory diseases1,2. One of these elements may be short-chain fatty acids (SCFAs), which are produced by fermentation of dietary fibre by intestinal microbiota. A feature of human ulcerative colitis and other colitic diseases is a change in ‘healthy’ microbiota such as Bifidobacterium and Bacteriodes3, and a concurrent reduction in SCFAs4. Moreover, increased intake of fermentable dietary fibre, or SCFAs, seems to be clinically beneficial in the treatment of colitis5-9. SCFAs bind the G-protein-coupled receptor 43 (GPR43, also known as FFAR2)10,11, and here we show that SCFA–GPR43 interactions profoundly affect inflammatory responses. Stimulation of GPR43 by SCFAs was necessary for the normal resolution of certain inflammatory responses, because GPR43-deficient (Gpr43−/−) mice showed exacerbated or unresolving inflammation in models of colitis, arthritis and asthma. This seemed to relate to increased production of inflammatory mediators by Gpr43−/− immune cells, and increased immune cell recruitment. Germ-free mice, which are devoid of bacteria and express little or no SCFAs, showed a similar dysregulation of certain inflammatory responses. GPR43 binding of SCFAs potentially provides a molecular link between diet, gastrointestinal bacterial metabolism, and immune and inflammatory responses. PMID:19865172

  15. Exaggerated inflammatory response of primary human myeloid dendritic cells to lipopolysaccharide in patients with inflammatory bowel disease.

    Science.gov (United States)

    Baumgart, D C; Thomas, S; Przesdzing, I; Metzke, D; Bielecki, C; Lehmann, S M; Lehnardt, S; Dörffel, Y; Sturm, A; Scheffold, A; Schmitz, J; Radbruch, A

    2009-09-01

    Inflammatory bowel disease (IBD) results from a breakdown of tolerance towards the indigenous flora in genetically susceptible hosts. Failure of dendritic cells (DC) to interpret molecular microbial patterns appropriately when directing innate and adaptive immune responses is conceivable. Primary (conventional, non-monocyte generated) CD1c(+)CD11c(+)CD14(-)CD16(-)CD19(-) myeloid blood or mucosal dendritic cells (mDC) from 76 patients with Crohn's disease (CD) or ulcerative colitis (UC) in remission, during flare-ups (FU) and 76 healthy or non-IBD controls were analysed by fluorescence activated cell sorter (FACS) flow cytometry and real-time polymerase chain reaction. Cytokine secretion of freshly isolated, cultured and lipopolysaccharide (LPS)-stimulated highly purified mDC (purity >95%) was assessed using cytometric bead arrays (CBA). More cultured and stimulated circulating mDC express CD40 in IBD patients. Stimulated circulating mDC from IBD patients secrete significantly more tumour necrosis factor (TNF)-alpha and interleukin (IL)-8. Toll-like receptor (TLR)-4 expression by mDC was higher in remission and increased significantly in flaring UC and CD patients compared with remission (P up more LPS and the uptake begins earlier compared with controls (P expressing mucosal mDC is significantly greater in UC and CD compared with non-IBD controls (P < 0.001 versus P < 0.01, respectively). Our data suggest an aberrant LPS response of mDC in IBD patients, resulting in an inflammatory phenotype and possibly intestinal homing in acute flares.

  16. Priming astrocytes with TNF enhances their susceptibility to Trypanosoma cruzi infection and creates a self-sustaining inflammatory milieu.

    Science.gov (United States)

    Silva, Andrea Alice; Silva, Rafael Rodrigues; Gibaldi, Daniel; Mariante, Rafael Meyer; Dos Santos, Jessica Brandão; Pereira, Isabela Resende; Moreira, Otacílio Cruz; Lannes-Vieira, Joseli

    2017-09-06

    , anti-TNF therapy reduced the number of amastigote nests in the brain. Our data implicate TNF as a promoter of T. cruzi invasion of mouse and human astrocytes. Moreover, the TNF-enriched inflammatory milieu and enhanced TNFR1 expression may favor TNF signaling, astrocyte colonization by T. cruzi and egression of trypomastigotes. Therefore, in T. cruzi infection, a self-sustaining TNF-induced inflammatory circuit may perpetuate the parasite cycle in the CNS and ultimately promote cytokine-driven behavioral alterations.

  17. Interaction of inflammatory and anti-inflammatory responses in microglia by Staphylococcus aureus-derived lipoteichoic acid

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Bor-Ren [Department of Neurosurgery, Buddhist Tzu Chi General Hospital, Taichung Branch, Taichung, Taiwan (China); Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan (China); Tsai, Cheng-Fang [Department of Biotechnology, Asia University, Taichung, Taiwan (China); Lin, Hsiao-Yun [Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan (China); Tseng, Wen-Pei [Graduate Institute of Sports and Health, National Changhua University of Education, Changhua County, Taiwan (China); Huang, Shiang-Suo [Department of Pharmacology and Institute of Medicine, College of Medicine, Chung Shan Medical University, Taiwan (China); Wu, Chi-Rei [Graduate Institute of Chinese Pharmaceutical Sciences, College of Pharmacy, China Medical University, Taiwan (China); Lin, Chingju [Department of Physiology, School of Medicine, China Medical University, Taichung, Taiwan (China); Yeh, Wei-Lan [Cancer Research Center, Department of Medical Research, Changhua Christian Hospital, Changhua, Taiwan (China); Lu, Dah-Yuu, E-mail: dahyuu@mail.cmu.edu.tw [Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan (China)

    2013-05-15

    We investigated the interaction between proinflammatory and inflammatory responses caused by Staphylococcus aureus-derived lipoteichoic acid (LTA) in primary cultured microglial cells and BV-2 microglia. LTA induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels increase in a concentration- and time-dependent manner. Meanwhile, LTA also increased nitric oxide (NO) and PGE{sub 2} production in microglia. Administration of TLR2 antagonist effectively inhibited LTA-induced NO, iNOS, and COX-2 expression. Moreover, treatment of cells with LTA caused a time-dependent activation of ERK, p38, JNK, as well as AKT. We also found that LTA-induced iNOS and COX-2 up-regulation were attenuated by p38, JNK, and PI3-kinase inhibitors. On the other hand, LTA-enhanced HO-1 expression was attenuated by p38 and PI3-kinase inhibitors. Treatment of cells with NF-κB and AP-1 inhibitors antagonized LTA-induced iNOS and COX-2 expression. However, only NF-κB inhibitors reduced LTA-induced HO-1 expression in microglia. Furthermore, stimulation of cells with LTA also activated IκBα phosphorylation, p65 phosphorylation at Ser{sup 536}, and c-Jun phosphorylation. Moreover, LTA-induced increases of κB-DNA and AP-1-DNA binding activity were inhibited by p38, JNK, and PI3-kinase inhibitors. HO-1 activator CoPP IX dramatically reversed LTA-induced iNOS expression. Our results provided mechanisms linking LTA and inflammation/anti-inflammation, and indicated that LTA plays a regulatory role in microglia activation. - Highlights: • LTA causes an increase in iNOS, COX-2, and HO-1 expression in microglia. • LTA induces iNOS and COX-2 expression through TLR-2/NF-κB and AP-1 pathways. • HO-1 expression is regulated through p38, JNK, PI3K/AKT and AP-1 pathways. • Induced HO-1 reduces LTA-induced iNOS expression. • LTA plays a regulatory role on inflammatory/anti-inflammatory responses.

  18. An Algorithm for Systemic Inflammatory Response Syndrome Criteria-Based Prediction of Sepsis in a Polytrauma Cohort.

    Science.gov (United States)

    Lindner, Holger A; Balaban, Ümniye; Sturm, Timo; Weiß, Christel; Thiel, Manfred; Schneider-Lindner, Verena

    2016-12-01

    Lifesaving early distinction of infectious systemic inflammatory response syndrome, known as "sepsis," from noninfectious systemic inflammatory response syndrome is challenging in the ICU because of high systemic inflammatory response syndrome prevalence and lack of specific biomarkers. The purpose of this study was to use an automatic algorithm to detect systemic inflammatory response syndrome criteria (tachycardia, tachypnea, leukocytosis, and fever) in surgical ICU patients for ICU-wide systemic inflammatory response syndrome prevalence determination and evaluation of algorithm-derived systemic inflammatory response syndrome descriptors for sepsis prediction and diagnosis in a polytrauma cohort. Cross-sectional descriptive study and retrospective cohort study. Electronic medical records of a tertiary care center's surgical ICU, 2006-2011. All ICU admissions and consecutive polytrauma admissions. None. Average prevalence of conventional systemic inflammatory response syndrome (≥ 2 criteria met concomitantly) from cross-sectional application of the algorithm to all ICU patients and each minute of the study period was 43.3%. Of 256 validated polytrauma patients, 85 developed sepsis (33.2%). Three systemic inflammatory response syndrome descriptors summarized the 24 hours after admission and before therapy initiation: 1) systemic inflammatory response syndrome criteria average for systemic inflammatory response syndrome quantification over time, 2) first-to-last minute difference for trend detection, and 3) change count reflecting systemic inflammatory response syndrome criteria fluctuation. Conventional systemic inflammatory response syndrome for greater than or equal to 1 minute had 91% sensitivity and 19% specificity, whereas a systemic inflammatory response syndrome criteria average cutoff value of 1.72 had 51% sensitivity and 77% specificity for sepsis prediction. For sepsis diagnosis, systemic inflammatory response syndrome criteria average and first

  19. Biological response modifiers and their potential use in the treatment of inflammatory skin diseases

    DEFF Research Database (Denmark)

    Villadsen, Louise S; Skov, Lone; Baadsgaard, Ole

    2003-01-01

    and fewer side-effects than the current systemic therapies now used for severe psoriasis, contact dermatitis and atopic dermatitis. In the pathogenesis of inflammatory skin diseases, the immune system plays a pivotal role, and this is where biological response modifiers such as monoclonal antibodies......In recent years, a more detailed understanding of the pathogenesis of several inflammatory skin diseases, combined with the developments within biotechnology, has made it possible to design more selective response modifiers. Biological response modifiers hold the potential for greater effectiveness......, recombinant cytokines, or fusion proteins may be effective. Several biological response modifiers have already shown positive results in phase II/III clinical trials in skin diseases, and many new biological response modifiers are in progress....

  20. The Inflammatory Response to Miniaturised Extracorporeal Circulation: A Review of the Literature

    Directory of Open Access Journals (Sweden)

    Hunaid A. Vohra

    2009-01-01

    Full Text Available Conventional cardiopulmonary bypass can trigger a systemic inflammatory response syndrome similar to sepsis. Aetiological factors include surgical trauma, reperfusion injury, and, most importantly, contact of the blood with the synthetic surfaces of the heart-lung machine. Recently, a new cardiopulmonary bypass system, mini-extracorporeal circulation (MECC, has been developed and has shown promising early results in terms of reducing this inflammatory response. It has no venous reservoir, a reduced priming volume, and less blood-synthetic interface. This review focuses on the inflammatory and clinical outcomes of using MECC and compares these to conventional cardio-pulmonary bypass (CCPB. MECC has been shown to reduce postoperative cytokines levels and other markers of inflammation. In addition, MECC reduces organ damage, postoperative complications and the need for blood transfusion. MECC is a safe and viable perfusion option and in certain circumstances it is superior to CCPB.

  1. Managing the inflammatory response after cardiopulmonary bypass: review of the studies in animal models

    Science.gov (United States)

    Liguori, Gabriel Romero; Kanas, Alexandre Fligelman; Moreira, Luiz Felipe Pinho

    2014-01-01

    Objective To review studies performed in animal models that evaluated therapeutic interventions to inflammatory response and microcirculatory changes after cardiopulmonary bypass. Methods It was used the search strategy ("Cardiopulmonary Bypass" (MeSH)) and ("Microcirculation" (MeSH) or "Inflammation" (MeSH) or "Inflammation Mediators" (MeSH)). Repeated results, human studies, non-English language articles, reviews and studies without control were excluded. Results Blood filters, system miniaturization, specific primers regional perfusion, adequate flow and temperature and pharmacological therapies with anticoagulants, vasoactive drugs and anti-inflammatories reduced changes in microcirculation and inflammatory response. Conclusion Demonstrated efficacy in animal models establishes a perspective for evaluating these interventions in clinical practice. PMID:24896169

  2. Cardiovascular biomaterials: when the inflammatory response helps to efficiently restore tissue functionality?

    Science.gov (United States)

    Boccafoschi, F; Mosca, C; Cannas, M

    2014-04-01

    The evaluation of biological host response to implanted materials permits the determination of the safety and biocompatibility of biomedical devices, prostheses and biomaterials. Once a biomaterial is introduced into the body to a corresponding implant site, a sequence of events occurs promoting the activation of inflammatory mediators such as leukocytes and the release of signaling molecules such as cytokines and growth factors, evoking an inflammatory and wound healing process. This review examines the cellular and molecular mechanisms involved in the foreign body reaction, especially how cytokines impact the overall inflammatory response to devices. It also reviews how these events can be modulated by the physical and chemical properties of the biomaterials such as wettability, chemistry and geometry of surface. Particular attention is dedicated to the cardiovascular field, where the use of synthetic polymers has several limitations such as thrombogenicity and risk of infection. New materials and strategies to improve biomaterial characteristics are discussed. Copyright © 2012 John Wiley & Sons, Ltd.

  3. The effect of resuscitation strategy on the longitudinal immuno-inflammatory response to blunt trauma

    DEFF Research Database (Denmark)

    Bonde, Alexander; Nordestgaard, Ask Tybjærg; Kirial, Rasmus

    2017-01-01

    INTRODUCTION: Resuscitation strategies following blunt trauma have been linked to immuno-inflammatory complications leading to systemic inflammatory syndrome (SIRS), sepsis and multiple organ failure (MOF). The effect of resuscitation strategy on longitudinal inflammation marker trajectories is......, however, unknown. We hypothesized that the effect of resuscitation strategy extends beyond the trauma-related coagulopathy, perhaps affecting the longitudinal immuno-inflammatory response to injury. METHODS: We analyzed data prospectively collected for the Inflammation and Host Response to Injury (Glue...... Grant) study. Blood sampling for inflammation marker analyses from blunt trauma patients was done on admission days 0, 1, 4, 7, 14, 21 and 28 where applicable. Total volume transfused of packed red blood cells (PRBC), fresh frozen plasma (FFP), platelets (PLT), and crystalloids during the initial 48h...

  4. Industry specific sustainability benchmarks: an ECSF pilot bridging corporate sustainability with social responsible investments

    NARCIS (Netherlands)

    van der Woerd, K.F.; van den Brink, T.W.M.

    2004-01-01

    This paper investigates the state of the art with respect to sustainability reporting, its linkages with the corporations, internal measurement and monitoring systems and their combined impact on the quality of contemporary sustainability benchmarks, developed by SRI analysts and so-called rating

  5. Sustaining Health Care Interventions to Achieve Quality Care: What We Can Learn From Rapid Response Teams.

    Science.gov (United States)

    Stolldorf, Deonni P

    Rapid response team (RRT) adoption and implementation are associated with improved quality of care of patients who experience an unanticipated medical emergency. The sustainability of RRTs is vital to achieve long-term benefits of these teams for patients, staff, and hospitals. Factors required to achieve RRT sustainability remain unclear. This study examined the relationship between sustainability elements and RRT sustainability in hospitals that have previously implemented RRTs.

  6. Suppressive effects of pelargonidin on PolyPhosphate-mediated vascular inflammatory responses.

    Science.gov (United States)

    Lee, In-Chul; Bae, Jong-Sup

    2017-02-01

    Previous reports suggest that human endothelial cells-derived PolyPhosphate (PolyP) is one of the pro-inflammatory mediators. As a well-known red pigment and found in plants, Pelargonidin (PEL) has been known to have several biological activates which are beneficial for human health. This study was undertaken to investigate whether PEL can modulate PolyP-mediated inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice. The anti-inflammatory activities of PEL were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in PolyP-activated HUVECs and mice. In addition, the beneficial effects of PEL on survival rate in PolyP-injected mice. We found that PEL inhibits PolyP-mediated barrier disruption, the expressions of cell adhesion molecules, and leukocyte to HUVEC adhesion/migration. Interestingly, PolyP-induced NF-κB activation and the productions of TNF-α and IL-6 were inhibited by PEL in HUVECs. These anti-inflammatory functions of PEL were confirmed in PolyP injected mice. These results suggest that PEL have therapeutic potential for various systemic inflammatory diseases.

  7. Loss of the Inducible Hsp70 Delays the Inflammatory Response to Skeletal Muscle Injury and Severely Impairs Muscle Regeneration

    Science.gov (United States)

    Howard, Travis M.; Ahn, Bumsoo; Ferreira, Leonardo F.

    2013-01-01

    Skeletal muscle regeneration following injury is a highly coordinated process that involves transient muscle inflammation, removal of necrotic cellular debris and subsequent replacement of damaged myofibers through secondary myogenesis. However, the molecular mechanisms which coordinate these events are only beginning to be defined. In the current study we demonstrate that Heat shock protein 70 (Hsp70) is increased following muscle injury, and is necessary for the normal sequence of events following severe injury induced by cardiotoxin, and physiological injury induced by modified muscle use. Indeed, Hsp70 ablated mice showed a significantly delayed inflammatory response to muscle injury induced by cardiotoxin, with nearly undetected levels of both neutrophil and macrophage markers 24 hours post-injury. At later time points, Hsp70 ablated mice showed sustained muscle inflammation and necrosis, calcium deposition and impaired fiber regeneration that persisted several weeks post-injury. Through rescue experiments reintroducing Hsp70 intracellular expression plasmids into muscles of Hsp70 ablated mice either prior to injury or post-injury, we confirm that Hsp70 optimally promotes muscle regeneration when expressed during both the inflammatory phase that predominates in the first four days following severe injury and the regenerative phase that predominates thereafter. Additional rescue experiments reintroducing Hsp70 protein into the extracellular microenvironment of injured muscles at the onset of injury provides further evidence that Hsp70 released from damaged muscle may drive the early inflammatory response to injury. Importantly, following induction of physiological injury through muscle reloading following a period of muscle disuse, reduced inflammation in 3-day reloaded muscles of Hsp70 ablated mice was associated with preservation of myofibers, and increased muscle force production at later time points compared to WT. Collectively our findings indicate that

  8. Expression of Drosophila adenosine deaminase in immune cells during inflammatory response.

    Directory of Open Access Journals (Sweden)

    Milena Novakova

    Full Text Available Extra-cellular adenosine is an important regulator of inflammatory responses. It is generated from released ATP by a cascade of ectoenzymes and degraded by adenosine deaminase (ADA. There are two types of enzymes with ADA activity: ADA1 and ADGF/ADA2. ADA2 activity originates from macrophages and dendritic cells and is associated with inflammatory responses in humans and rats. Drosophila possesses a family of six ADGF proteins with ADGF-A being the main regulator of extra-cellular adenosine during larval stages. Herein we present the generation of a GFP reporter for ADGF-A expression by a precise replacement of the ADGF-A coding sequence with GFP using homologous recombination. We show that the reporter is specifically expressed in aggregating hemocytes (Drosophila immune cells forming melanotic capsules; a characteristic of inflammatory response. Our vital reporter thus confirms ADA expression in sites of inflammation in vivo and demonstrates that the requirement for ADA activity during inflammatory response is evolutionary conserved from insects to vertebrates. Our results also suggest that ADA activity is achieved specifically within sites of inflammation by an uncharacterized post-transcriptional regulation based mechanism. Utilizing various mutants that induce melanotic capsule formation and also a real immune challenge provided by parasitic wasps, we show that the acute expression of the ADGF-A protein is not driven by one specific signaling cascade but is rather associated with the behavior of immune cells during the general inflammatory response. Connecting the exclusive expression of ADGF-A within sites of inflammation, as presented here, with the release of energy stores when the ADGF-A activity is absent, suggests that extra-cellular adenosine may function as a signal for energy allocation during immune response and that ADGF-A/ADA2 expression in such sites of inflammation may regulate this role.

  9. Transcription factors early growth response gene (Egr) 2 and 3 control inflammatory responses of tolerant T cells.

    Science.gov (United States)

    Omodho, Becky; Miao, Tizong; Symonds, Alistair L J; Singh, Randeep; Li, Suling; Wang, Ping

    2018-01-03

    Impaired proliferation and production of IL2 are the hallmarks of experimental T cell tolerance. However, in most autoimmune diseases, auto-reactive T cells do not display hyper proliferation, but inflammatory phenotypes. We have now demonstrated that the transcription factors Egr2 and 3 are important for the control of inflammatory cytokine production by tolerant T cells, but not for tolerance induction. In the absence of Egr2 and 3, T cell tolerance, as measured by impaired proliferation and production of IL2, can still be induced, but tolerant T cells produced high levels of inflammatory cytokines. Egr2 and 3 regulate expression of differentiation repressors and directly inhibit T-bet function in T cells. Indeed, decreased expression of differentiation repressors, such as Id3 and Tcf1, and increased expression of inflammatory transcription factors, such as RORγt and Bhlhe40 were found in Egr2/3 deficient T cells under tolerogenic conditions. In addition, T-bet was co-expressed with Egr2 in tolerant T cells and Egr2/3 defects leads to production of high levels of IFNγ in tolerant T cells. Our findings demonstrated that despite impaired proliferation and IL2 production, tolerant T cells can display inflammatory responses in response to antigen stimulation and this is controlled at least partly by Egr2 and 3. © 2017 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

  10. Elevation in inflammatory serum biomarkers predicts response to trastuzumab-containing therapy.

    Directory of Open Access Journals (Sweden)

    Ahmed A Alkhateeb

    Full Text Available Approximately half of all HER2/neu-overexpressing breast cancer patients do not respond to trastuzumab-containing therapy. Therefore, there remains an urgent and unmet clinical need for the development of predictive biomarkers for trastuzumab response. Recently, several lines of evidence have demonstrated that the inflammatory tumor microenvironment is a major contributor to therapy resistance in breast cancer. In order to explore the predictive value of inflammation in breast cancer patients, we measured the inflammatory biomarkers serum ferritin and C-reactive protein (CRP in 66 patients immediately before undergoing trastuzumab-containing therapy and evaluated their progression-free and overall survival. The elevation in pre-treatment serum ferritin (>250 ng/ml or CRP (>7.25 mg/l was a significant predictor of reduced progression-free survival and shorter overall survival. When patients were stratified based on their serum ferritin and CRP levels, patients with elevation in both inflammatory biomarkers had a markedly poorer response to trastuzumab-containing therapy. Therefore, the elevation in inflammatory serum biomarkers may reflect a pathological state that decreases the clinical efficacy of this therapy. Anti-inflammatory drugs and life-style changes to decrease inflammation in cancer patients should be explored as possible strategies to sensitize patients to anti-cancer therapeutics.

  11. The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology.

    Science.gov (United States)

    Millar, Jonathan E; Fanning, Jonathon P; McDonald, Charles I; McAuley, Daniel F; Fraser, John F

    2016-11-28

    Extracorporeal membrane oxygenation (ECMO) is a technology capable of providing short-term mechanical support to the heart, lungs or both. Over the last decade, the number of centres offering ECMO has grown rapidly. At the same time, the indications for its use have also been broadened. In part, this trend has been supported by advances in circuit design and in cannulation techniques. Despite the widespread adoption of extracorporeal life support techniques, the use of ECMO remains associated with significant morbidity and mortality. A complication witnessed during ECMO is the inflammatory response to extracorporeal circulation. This reaction shares similarities with the systemic inflammatory response syndrome (SIRS) and has been well-documented in relation to cardiopulmonary bypass. The exposure of a patient's blood to the non-endothelialised surface of the ECMO circuit results in the widespread activation of the innate immune system; if unchecked this may result in inflammation and organ injury. Here, we review the pathophysiology of the inflammatory response to ECMO, highlighting the complex interactions between arms of the innate immune response, the endothelium and coagulation. An understanding of the processes involved may guide the design of therapies and strategies aimed at ameliorating inflammation during ECMO. Likewise, an appreciation of the potentially deleterious inflammatory effects of ECMO may assist those weighing the risks and benefits of therapy.

  12. Reduction of the inflammatory response in patients undergoing minimally invasive coronary artery bypass grafting

    NARCIS (Netherlands)

    Gu, YJ; Mariani, MA; van Oeveren, W; Grandjean, JG; Boonstra, PW

    Background. The aim of this prospective study was to determine whether the inflammation-associated clinical morbidity as well as the subclinical markers of the inflammatory response are reduced in patients who undergo minimally invasive coronary artery bypass grafting without cardiopulmonary bypass.

  13. Exploring the Risk Factors for Sudden Infant Deaths and Their Role in Inflammatory Responses to Infection

    Science.gov (United States)

    Blackwell, Caroline; Moscovis, Sophia; Hall, Sharron; Burns, Christine; Scott, Rodney J.

    2015-01-01

    The risk factors for sudden infant death syndrome (SIDS) parallel those associated with susceptibility to or severity of infectious diseases. There is no evidence that a single infectious agent is associated with SIDS; the common thread appears to be induction of inflammatory responses to infections. In this review, interactions between genetic and environmental risk factors for SIDS are assessed in relation to the hypothesis that many infant deaths result from dysregulation of inflammatory responses to “minor” infections. Risk factors are assessed in relation to three important stages of infection: (1) bacterial colonization (frequency or density); (2) induction of temperature-dependent toxins; (3) induction or control of inflammatory responses. In this article, we review the interactions among risk factors for SIDS for their effects on induction or control of inflammatory responses. The risk factors studied are genetic factors (sex, cytokine gene polymorphisms among ethnic groups at high or low risk of SIDS); developmental stage (changes in cortisol and testosterone levels associated with 2- to 4-month age range); environmental factors (virus infection, exposure to cigarette smoke). These interactions help to explain differences in the incidences of SIDS observed between ethnic groups prior to public health campaigns to reduce these infant deaths. PMID:25798137

  14. The levels of RAC3 expression are up regulated by TNF in the inflammatory response

    Directory of Open Access Journals (Sweden)

    Cecilia Viviana Alvarado

    2014-01-01

    Full Text Available RAC3 is a coactivator of glucocorticoid receptor and nuclear factor-κB (NF-κB that is usually over-expressed in tumors and which also has important functions in the immune system. We investigated the role of the inflammatory response in the control of RAC3 expression levels in vivo and in vitro. We found that inflammation regulates RAC3 levels. In mice, sub-lethal doses of lipopolysaccharide induce the increase of RAC3 in spleen and the administration of the synthetic anti-inflammatory glucocorticoid dexamethasone has a similar effect. However, the simultaneous treatment with both stimuli is mutually antagonistic. In vitro stimulation of the HEK293 cell line with tumor necrosis factor (TNF, one of the cytokines induced by lipopolysaccharide, also increases the levels of RAC3 mRNA and protein, which correlates with an enhanced transcription dependent on the RAC3 gene promoter. We found that binding of the transcription factor NF-κB to the RAC3 gene promoter could be responsible for these effects. Our results suggest that increase of RAC3 during the inflammatory response could be a molecular mechanism involved in the control of sensitivity to both pro- and anti-inflammatory stimuli in order to maintain the normal healthy course of the immune response.

  15. High-intensity interval training induces a modest systemic inflammatory response in active, young men

    Science.gov (United States)

    Zwetsloot, Kevin A; John, Casey S; Lawrence, Marcus M; Battista, Rebecca A; Shanely, R Andrew

    2014-01-01

    The purpose of this study was to determine: 1) the extent to which an acute session of high-intensity interval training (HIIT) increases systemic inflammatory cytokines and chemokines, and 2) whether 2 weeks of HIIT training alters the inflammatory response. Eight recreationally active males (aged 22±2 years) performed 2 weeks of HIIT on a cycle ergometer (six HIIT sessions at 8–12 intervals; 60-second intervals, 75-second active rest) at a power output equivalent to 100% of their predetermined peak oxygen uptake (VO2max). Serum samples were collected during the first and sixth HIIT sessions at rest and immediately, 15, 30, and 45 minutes post-exercise. An acute session of HIIT induced significant increases in interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α, and monocyte chemotactic protein-1 compared with rest. The concentrations of interferon-γ, granulocyte macrophage-colony-stimulating factor, and IL-1β were unaltered with an acute session of HIIT Two weeks of training did not alter the inflammatory response to an acute bout of HIIT exercise. Maximal power achieved during a VO2max test significantly increased 4.6%, despite no improvements in VO2max after 2 weeks of HIIT. These data suggest that HIIT exercise induces a small inflammatory response in young, recreationally active men; however, 2 weeks of HIIT does not alter this response. PMID:24520199

  16. Inflammatory responses to induced infectious endometritis in mares resistant or susceptible to persistent endometritis

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Woodward, Elizabeth; Bojesen, Anders Miki

    2012-01-01

    The objective of the study was to evaluate the gene expression of inflammatory cytokines (interleukin [IL]-1ß, IL-6, IL-8, IL-10, tumor necrosis factor [TNF]-a, IL-1 receptor antagonist [ra] and serum amyloid A (SAA) in endometrial tissue and circulating leukocytes in response to uterine inoculat...

  17. Treatment response in childhood asthma. An interplay of genes and inflammatory signals

    NARCIS (Netherlands)

    Vijverberg, S.J.H.|info:eu-repo/dai/nl/325847460

    2014-01-01

    Treatment response in asthmatic children Asthma is a chronic disease of the airways and the most common chronic disease among children. Inhaled corticosteroids (ICS) are the cornerstone of persistent asthma treatment and are thought to function due to their anti-inflammatory properties.

  18. Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome

    NARCIS (Netherlands)

    Iyer, Shankar S.; Pulskens, Wilco P.; Sadler, Jeffrey J.; Butter, Loes M.; Teske, Gwendoline J.; Ulland, Tyler K.; Eisenbarth, Stephanie C.; Florquin, Sandrine; Flavell, Richard A.; Leemans, Jaklien C.; Sutterwala, Fayyaz S.

    2009-01-01

    Dying cells are capable of activating the innate immune system and inducing a sterile inflammatory response. Here, we show that necrotic cells are sensed by the Nlrp3 inflammasome resulting in the subsequent release of the proinflammatory cytokine IL-1 beta. Necrotic cells produced by pressure

  19. Sarcopenia is associated with an increased inflammatory response to surgery in colorectal cancer

    NARCIS (Netherlands)

    Reisinger, Kostan W.; Derikx, Joep P. M.; van Vugt, Jeroen L. A.; Von Meyenfeldt, Maarten F.; Hulsewé, Karel W.; Olde Damink, Steven W. M.; Stoot, Jan H. M. B.; Poeze, Martijn

    2016-01-01

    Background & aims: Sarcopenia in gastrointestinal cancer has been associated with poor clinical outcome after surgery. The effect of low muscle mass on the inflammatory response to surgery has not been investigated, however skeletal muscle wasting in the context of cachexia is associated with a

  20. Topical Modulation of the Burn Wound Inflammatory Response to Improve Short and Long Term Outcomes

    Science.gov (United States)

    2015-10-15

    hypertrophic scar, p38, combat casualty, treatment, organ failure, systemic inflammatory response syndrome , thermal injury, wound model, intervention 3...follicle apoptosis.  We will complete our wound closure data for Pg004, Pg005, and Pg008. We will also examine the H&E slides and complete the data for

  1. Effects of IL-10 on systemic inflammatory responses during sublethal primate endotoxemia

    NARCIS (Netherlands)

    van der Poll, T.; Jansen, P. M.; Montegut, W. J.; Braxton, C. C.; Calvano, S. E.; Stackpole, S. A.; Smith, S. R.; Swanson, S. W.; Hack, C. E.; Lowry, S. F.; Moldawer, L. L.

    1997-01-01

    IL-10 protects mice from LPS-induced lethality. To determine the effects of IL-10 on LPS-induced inflammatory responses, six Papio anubis baboons were i.v. injected with a sublethal dose of LPS (Salmonella typhimurium; 500 microg/kg) directly preceded by either human rIL-10 (n = 3, 500 microg/kg) or

  2. Distinct inflammatory responses differentiate cerebral infarct from transient ischaemic attack.

    Science.gov (United States)

    Armstrong, Christopher W L; Bosio, Erika; Neil, Claire; Brown, Simon G A; Hankey, Graeme J; Fatovich, Daniel M

    2017-01-01

    We previously reported on a 26-year-old patient who presented early during a large and eventually fatal cerebral infarct. Microarray analysis of blood samples from this patient demonstrated initially up-regulated and subsequently down-regulated Granzyme B (GzmB) expression, along with progressive up-regulation of genes for S100 calcium binding protein A12 (S100A12) and matrix metalloproteinase 9 (MMP-9). To confirm these findings, we investigated these parameters in patients with suspected stroke presenting within 6h of symptom onset to a single centre. Blood samples were taken at enrolment, then 1h, 3h and 24h post-enrolment for the examination of cellular, protein and genetic changes. Patients with subsequently confirmed ischaemic (n=18) or haemorrhagic stroke (n=11) showed increased intracellular concentrations of GzmB in all cell populations investigated (CD8+, CD8- and Natural Killer [NK] cells). Infarct patients, however, demonstrated significantly reduced GzmB gene expression and increased circulating MMP-9 and S100A12 levels in contrast to transient ischaemic attack (TIA) patients or healthy controls. Furthermore, a pronounced neutrophilia was noted in the infarct and haemorrhage groups, while TIA patients (n=9) reflected healthy controls (n=10). These findings suggest a spectrum of immune response during stroke. TIA showed few immunological changes in comparison to infarct and haemorrhage, which demonstrated inhibition of GzmB production and a rise in neutrophil numbers and neutrophil-associated mediators. This implies a greater role of the innate immune system. These markers may provide novel targets for inhibition and reduction of secondary injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to Bacillus anthracis.

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    Jill K Terra

    2011-12-01

    Full Text Available Anthrax is a potentially fatal disease resulting from infection with Bacillus anthracis. The outcome of infection is influenced by pathogen-encoded virulence factors such as lethal toxin (LT, as well as by genetic variation within the host. To identify host genes controlling susceptibility to anthrax, a library of congenic mice consisting of strains with homozygous chromosomal segments from the LT-responsive CAST/Ei strain introgressed on a LT-resistant C57BL/6 (B6 background was screened for response to LT. Three congenic strains containing CAST/Ei regions of chromosome 11 were identified that displayed a rapid inflammatory response to LT similar to, but more severe than that driven by a LT-responsive allele of the inflammasome constituent NRLP1B. Importantly, increased response to LT in congenic mice correlated with greater resistance to infection by the Sterne strain of B. anthracis. The genomic region controlling the inflammatory response to LT was mapped to 66.36-74.67 Mb on chromosome 11, a region that encodes the LT-responsive CAST/Ei allele of Nlrp1b. However, known downstream effects of NLRP1B activation, including macrophage pyroptosis, cytokine release, and leukocyte infiltration could not fully explain the response to LT or the resistance to B. anthracis Sterne in congenic mice. Further, the exacerbated response in congenic mice is inherited in a recessive manner while the Nlrp1b-mediated response to LT is dominant. Finally, congenic mice displayed increased responsiveness in a model of sepsis compared with B6 mice. In total, these data suggest that allelic variation of one or more chromosome 11 genes in addition to Nlrp1b controls the severity of host response to multiple inflammatory stimuli and contributes to resistance to B. anthracis Sterne. Expression quantitative trait locus analysis revealed 25 genes within this region as high priority candidates for contributing to the host response to LT.

  4. The role of multiple negative social relationships in inflammatory cytokine responses to a laboratory stressor

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    Sunmi Song

    2015-06-01

    Full Text Available The present study examined the unique impact of perceived negativity in multiple social relationships on endocrine and inflammatory responses to a laboratory stressor. Via hierarchical cluster analysis, those who reported negative social exchanges across relationships with a romantic partner, family, and their closest friend had higher mean IL-6 across time and a greater increase in TNF-α from 15 min to 75 min post stress. Those who reported negative social exchanges across relationships with roommates, family, and their closest friend showed greater IL-6 responses to stress. Differences in mean IL-6 were accounted for by either depressed mood or hostility, whereas differences in the cytokine stress responses remained significant after controlling for those factors. Overall, this research provides preliminary evidence to suggest that having multiple negative relationships may exacerbate acute inflammatory responses to a laboratory stressor independent of hostility and depressed mood.

  5. Induction of intestinal pro-inflammatory immune responses by lipoteichoic acid

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    Zadeh Mojgan

    2012-03-01

    Full Text Available Abstract Background The cellular and molecular mechanisms of inflammatory bowel disease are not fully understood; however, data indicate that uncontrolled chronic inflammation induced by bacterial gene products, including lipoteichoic acid (LTA, may trigger colonic inflammation resulting in disease pathogenesis. LTA is a constituent glycolipid of Gram-positive bacteria that shares many inflammatory properties with lipopolysaccharide and plays a critical role in the pathogenesis of severe inflammatory responses via Toll-like receptor 2. Accordingly, we elucidate the role of LTA in immune stimulation and induced colitis in vivo. Methods To better understand the molecular mechanisms utilized by the intestinal microbiota and their gene products to induce or subvert inflammation, specifically the effect(s of altered surface layer protein expression on the LTA-mediated pro-inflammatory response, the Lactobacillus acidophilus surface layer protein (Slp genes encoding SlpB and SlpX were deleted resulting in a SlpB- and SlpX- mutant that continued to express SlpA (assigned as NCK2031. Results Our data show profound activation of dendritic cells by NCK2031, wild-type L. acidophilus (NCK56, and purified Staphylococcus aureus-LTA. In contrary to the LTA-deficient strain NCK2025, the LTA-expressing strains NCK2031 and NCK56, as well as S. aureus-LTA, induce pro-inflammatory innate and T cell immune responses in vivo. Additionally, neither NCK2031 nor S. aureus-LTA supplemented in drinking water protected mice from DSS-colitis, but instead, induced significant intestinal inflammation resulting in severe colitis and tissue destruction. Conclusions These findings suggest that directed alteration of two of the L. acidophilus NCFM-Slps did not ameliorate LTA-induced pro-inflammatory signals and subsequent colitis.

  6. HMGB1/TLR4 signaling induces an inflammatory response following high-pressure renal pelvic perfusion in a porcine model.

    Science.gov (United States)

    Shao, Yi; Sha, Minglei; Chen, Lei; Li, Deng; Lu, Jun; Xia, Shujie

    2016-11-01

    Percutaneous nephrolithotomy (PCNL) causes a rapid increase in renal pelvic pressure in the kidney, which induces an inflammatory response. High-mobility group box-1 (HMGB1) is known to trigger the recruitment of inflammatory cells and the release of proinflammatory cytokines following ischemia reperfusion injury in the kidney, but the contribution of HMGB1 to the inflammatory response following high-pressure renal pelvic perfusion has not been investigated. In this study, high-pressure renal pelvic perfusion was induced in anesthetized pigs to examine the effect of HMGB1 on the inflammatory response. HMGB1 levels in the kidney increased following high-pressure renal pelvic perfusion, together with elevated levels of inflammatory cytokines in the plasma and kidney and an accumulation of neutrophils and macrophages. Inhibition of HMGB1 alleviated this inflammatory response while perfusion with recombinant HMGB1 had an augmentative effect, confirming the involvement of HMGB1 in the inflammatory response to high-pressure renal pelvic perfusion. HMGB1 regulated the inflammatory response by activating Toll-like receptor 4 (TLR4) signaling. In conclusion, this study has demonstrated that HMGB1/TLR4 signaling contributes to the inflammatory response following high-pressure renal pelvic perfusion in a porcine model and has implications for the management of inflammation after PCNL. Copyright © 2016 the American Physiological Society.

  7. Effects of Immunosuppressants on Immune Response to Vaccine in Inflammatory Bowel Disease

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    Yuan Cao; Di Zhao; An-Tao Xu; Jun Shen; Zhi-Hua Ran

    2015-01-01

    Objective: To evaluate the response rate to vaccination in different treatment groups (nonimmunosuppressants and immunosuppressants). Data Sources: We completed an online systematic search using PubMed to identify all articles published in English between January 1990 and December 2013 assessing the effect of the response rate to vaccination in different treatment groups (with and without immunomodulators). The following terms were used: "inflammatory bowel disease (IBD)" OR "Crohn′s dise...

  8. Sustainability Management in Agribusiness: Challenges, Concepts, Responsibilities and Performance

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    Nina Friedrich

    2012-12-01

    Full Text Available The idea of sustainable management has recently gained growing attention in the agribusiness sector. This is mainly due to a widespread discontent with the industrialization of agricultural production and food processing and growing public pressure on agribusiness firms to implement more sustainable management practices. In this paper we present the results of an explorative empirical study of sustainability management in German agribusiness firms. The study shows that agribusiness firms have developed a broad understanding of sustainability management and perceive a multi-facetted spectrum of societal demands they have to meet. The most important arguments for implementing more sustainable management practices are that companies have to make sure that they are trusted by society in the long run and that the perception of a company by external stakeholders has become more and more important. The companies surveyed know quite a number of sustainability programmes and standards, but the number of companies that actually participate in these initiatives is much smaller. Nonetheless, the majority of the respondents feels that their company is more successful with regard to sustainability management than industry average.

  9. Contribution of pharmaceuticals, fecal bacteria and endotoxin to the inflammatory responses to inland waters.

    Science.gov (United States)

    El Marghani, Ahmed; Pradhan, Ajay; Seyoum, Asmerom; Khalaf, Hazem; Ros, Torbjön; Forsberg, Lars-Håkan; Nermark, Tomas; Osterman, Lisa; Wiklund, Ulf; Ivarsson, Per; Jass, Jana; Olsson, Per-Erik

    2014-08-01

    The increasing contamination of freshwater with pharmaceuticals, surfactants, pesticides and other organic compounds are of major concern. As these contaminants are detected at trace levels in the environment it is important to determine if they elicit biological responses at the observed levels. In addition to chemical pollutants, there is also a concern for increasing levels of bacteria and other microorganisms in freshwater systems. In an earlier study, we observed the activation of inflammatory systems downstream of a wastewater treatment plant (WWTP) in southern Sweden. We also observed that the water contained unidentified components that were pro-inflammatory and potentiated the immune response in human urinary bladder epithelial cells. In order to determine if these effects were unique for the studied site or represent a common response in Swedish water, we have now performed a study on three WWTPs and their recipient waters in central Sweden. Analysis of immune responses in urinary bladder epithelial cells, monocyte-like cells and blood mononuclear cells confirm that these waters activate the immune system as well as induce pro-inflammatory responses. The results indicate that the cytokine profiles correlate to the endotoxin load of the waters rather than to the levels of pharmaceuticals or culturable bacteria load, suggesting that measurements of endotoxin levels and immune responses would be a valuable addition to the analysis of inland waters. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Training increases anabolic response and reduces inflammatory response to a single practice in elite male adolescent volleyball players.

    Science.gov (United States)

    Nemet, Dan; Portal, Shawn; Zadik, Zvi; Pilz-Burstein, Rutie; Adler-Portal, Dana; Meckel, Yoav; Eliakim, Alon

    2012-01-01

    We examined the effect of training on hormonal and inflammatory response to a single volleyball practice in elite adolescent players. Fourteen male, elite, national team-level, Israeli volleyball players (age, 16.3±1.1 years, Tanner stage 4-5) participated in the study. Blood samples were collected before and immediately after a typical 60-min volleyball practice, before and after 7 weeks of training during the initial phases of the volleyball season. Hormonal measurements included the anabolic hormones growth hormone (GH), insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, and testosterone; the catabolic hormone cortisol; the pro-inflammatory markers interleukin (IL) 6, and the anti-inflammatory marker IL-1 receptor antagonist. Training led to a significant improvement of both anaerobic and aerobic properties. Before the training intervention, the typical volleyball practice was associated with a significant increase of GH and testosterone and also with a significant increase of IL-6. Training resulted in a significantly greater GH response (ΔGH, 2.5±2.4 vs. 4.7±3.0 ng/mL, before and after training, respectively; pvolleyball practice. The results suggest that, along with the improvement of anaerobic and aerobic characteristics, training leads to a greater anabolic and reduced inflammatory response to exercise.

  11. Hypoxic treatment of human dual placental perfusion induces a preeclampsia-like inflammatory response.

    Science.gov (United States)

    Jain, Arjun; Schneider, Henning; Aliyev, Eldar; Soydemir, Fatimah; Baumann, Marc; Surbek, Daniel; Hediger, Matthias; Brownbill, Paul; Albrecht, Christiane

    2014-08-01

    Preeclampsia is a human pregnancy-specific disorder characterized by a placental pro-inflammatory response in combination with an imbalance of angiogenic factors and clinical symptoms, including hypertension and proteinuria. Insufficient uteroplacental oxygenation in preeclampsia due to impaired trophoblast invasion during placentation is believed to be responsible for many of the molecular events leading to the clinical manifestations of this disease. We investigated the use of hypoxic treatment of the dual placental perfusion system as a model for preeclampsia. A modified perfusion technique allowed us to achieve a mean soluble oxygen tension within the intervillous space (IVS) of 5-7% for normoxia and preeclampsia). We assayed for the levels of different inflammatory cytokines, oxidative stress markers, as well as other factors, such as endothelin (ET)-1 that are known to be implicated as part of the inflammatory response in preeclampsia. Our results show a significant increase under hypoxia in the levels of different inflammatory cytokines, including IL-6 (P=0.002), IL-8 (Ppreeclampsia. This would therefore provide a powerful tool for studying and further delineating the molecular mechanisms involved in the underlying pathophysiology of preeclampsia.

  12. The Acute Inflammatory Response to Absorbed Collagen Sponge Is Not Enhanced by BMP-2

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    Hairong Huang

    2017-02-01

    Full Text Available Absorbed collagen sponge (ACS/bone morphogenetic protein-2 (BMP-2 are widely used in clinical practise for bone regeneration. However, the application of this product was found to be associated with a significant pro-inflammatory response, particularly in the early phase after implantation. This study aimed to clarify if the pro-inflammatory activities, associated with BMP-2 added to ACS, were related to the physical state of the carrier itself, i.e., a wet or a highly dehydrated state of the ACS, to the local degree of vascularisation and/or to local biomechanical factors. ACS (0.8 cm diameter/BMP-2 were implanted subcutaneously in the back of 12 eight-week-old Sprague Dawley rats. Two days after surgery, the implanted materials were retrieved and analysed histologically and histomorphometrically. The acute inflammatory response following implantation of ACS was dependent of neither the presence or absence of BMP-2 nor the degree of vascularization in the surrounding tissue nor the hydration state (wet versus dry of the ACS material at the time of implantation. Differential micro biomechanical factors operating at the implantation site appeared to have an influence on the thickness of inflammation. We conclude that the degree of the early inflammatory response of the ACS/BMP-2 may be associated with the physical and chemical properties of the carrier material itself.

  13. Decoy Receptor 3 Improves Survival in Experimental Sepsis by Suppressing the Inflammatory Response and Lymphocyte Apoptosis.

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    DongYu Liang

    Full Text Available Unbalanced inflammatory response and lymphocyte apoptosis is associated with high mortality in septic patients. Decoy receptor 3 (DcR3, a member of the tumor necrosis factor receptor superfamily, is an anti-inflammatory and anti-apoptotic factor. Recently, DcR3 expression was found to be increased in septic patients. This study evaluated the therapeutic effect and mechanisms of DcR3 on cecal ligation and puncture (CLP-induced sepsis in mice.C57BL/6 mice were subjected to CLP-induced polymicrobial sepsis. DcR3 Fc was intravenously injected 30 min before and 6 h after CLP. Bacterial clearance, cytokine production, histology, lymphocyte apoptosis and survival were evaluated. Furthermore, we investigated the systemic effects of DcR3 in in vitro lymphocyte apoptosis regulation.Our results demonstrated that DcR3 protein treatments significantly improved survival in septic mice (p <0.05. Treatment with DcR3 protein significantly reduced the inflammatory response and decreased lymphocyte apoptosis in the thymus and spleen. Histopathological findings of the lung and liver showed milder impairment after DcR3 administration. In vitro experiments showed that DcR3 Fc inhibited Fas-FasL mediated lymphocyte apoptosis.Treatment with the DcR3 protein protects mice from sepsis by suppressing the inflammatory response and lymphocyte apoptosis. DcR3 protein may be useful in treatment of sepsis.

  14. Inflammatory response of a prostate stromal cell line induced by Trichomonas vaginalis.

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    Im, S J; Han, I H; Kim, J H; Gu, N Y; Seo, M Y; Chung, Y H; Ryu, J S

    2016-04-01

    While Trichomonas vaginalis, a cause of sexually transmitted infection, is known as a surface-dwelling protozoa, trichomonads have been detected in prostatic tissue from benign prostatic hyperplasia and prostatitis by immunoperoxidase assay or PCR. However, the immune response of prostate stromal cells infected with T. vaginalis has not been investigated. Our objective was to investigate whether T. vaginalis could induce an inflammatory response in prostate stromal cells. Incubation of a human prostate stromal myofibroblast cells (WPMY-1) with live T. vaginalis T016 increased expression of the inflammatory chemokines CXCL8 and CCL2. In addition, TLR4, ROS, MAPK and NF-κB expression increased, while inhibitors of TLR4, ROS, MAPKs and NF-κB reduced CXCL8 and CCL2 production. Medium conditioned by incubation of WPMY-1 cells with T. vaginalis stimulated the migration of human neutrophils and monocytes (THP-1 cells). We conclude that T. vaginalis increases CXCL8 and CCL2 production by human prostate stromal cells by activating TLR4, ROS, MAPKs and NF-κB, and this in turn attracts neutrophils and monocytes and leads to an inflammatory response. This study is the first attempt to demonstrate an inflammatory reaction in prostate stromal cells caused by T. vaginalis. © 2016 John Wiley & Sons Ltd.

  15. Influence of inflammatory response, infection, and pulmonary function in cystic fibrosis.

    Science.gov (United States)

    Pereira, Leticia Cristina Radin; Moreira, Emilia Addison Machado; Bennemann, Gabriela Datsch; Moreno, Yara Maria Franco; Buss, Ziliani da Silva; Barbosa, Eliana; Ludwig-Neto, Norberto; Wilhelm Filho, Danilo; Fröde, Tânia Silvia

    2014-07-25

    Recurrent infections and activation of the inflammatory response affect the prognosis of cystic fibrosis (CF). We investigated the relationship between inflammatory response, infection, and pulmonary function in CF. A clinical-cross-sectional study was conducted with 86 subjects: control group (CG, n=31, the same age and sex of the CF group), and CF group (CFG, n=55, age: 1-16 years), further distributed into CFG negative or positive bacteriology (CFGB(-)/CFGB(+)), and CFG negative or positive Pseudomonas aeruginosa (CFGPa(-)/CFGPa(+)). Using the Wald test, multiple linear regression (95% confidence interval) was performed between CG and CFG, and between CG and each of the CF subgroups (CFGB(-)/CFGB(+) and CFGPa(-)/CFGPa(+)). The inflammatory markers evaluated were myeloperoxidase (MPO), adenosine deaminase (ADA) activities, interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), nitric oxide metabolites (NOx) levels, and total and differential leukocyte counts. After adjusting for sex and age, CFG compared to CG revealed an increase of MPO, IL-1β (PCFG (P=0.002), CFGB(-) (P=0.007), CFGB(+) (P=0.009), CFGPa(-) (P=0.004) and CFGPa(+) (P=0.020). NOx (P=0.001, PCFG. The inflammatory response characterized by the increase of MPO, IL-1β, and CRP is determinant for CF. Also leukocytosis due to neutrophilia determines the pulmonary function deficiency in this disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Unraveling inflammatory responses using systems genetics and gene-environment interactions in macrophages

    Science.gov (United States)

    Orozco, Luz D.; Bennett, Brian J.; Farber, Charles R.; Ghazalpour, Anatole; Pan, Calvin; Che, Nam; Wen, Pingzi; Qi, Hong Xiu; Mutukulu, Adonisa; Siemers, Nathan; Neuhaus, Isaac; Yordanova, Roumyana; Gargalovic, Peter; Pellegrini, Matteo; Kirchgessner, Todd; Lusis, Aldons J.

    2012-01-01

    SUMMARY Many common diseases have an important inflammatory component mediated in part by macrophages. Here we used a systems genetics strategy to examine the role of common genetic variation in macrophage responses to inflammatory stimuli. We examined genome-wide transcript levels in macrophages from 92 strains of the Hybrid Mouse Diversity Panel. We exposed macrophages to control media, bacterial lipopolysaccharide, or oxidized phospholipids. We performed association mapping under each condition and identified several thousand expression quantitative trait loci (eQTL), gene-by-environment interactions and several eQTL “hotspots” that specifically control LPS responses. We validated an eQTL hotspot in chromosome 8 using siRNA knock-down of candidate genes and identified the gene 2310061C15Rik, as a novel regulator of inflammatory responses in macrophages. We have created a public database where the data presented here can be used as a resource for understanding many common inflammatory traits which are modeled in the mouse, and for the dissection of regulatory relationships between genes. PMID:23101632

  17. Microbiota signalling through MyD88 is necessary for a systemic neutrophilic inflammatory response

    Science.gov (United States)

    Karmarkar, Dipti; Rock, Kenneth L

    2013-01-01

    In the present study, we have found that intestinal flora strongly influence peritoneal neutrophilic inflammatory responses to diverse stimuli, including pathogen-derived particles like zymosan and sterile irritant particles like crystals. When germ-free and flora-deficient (antibiotic-treated) mice are challenged with zymosan intraperitoneally, neutrophils are markedly impaired in their ability to extravasate from blood into the peritoneum. In contrast, in these animals, neutrophils can extravasate in response to an intraperitoneal injection of the chemokine, macrophage inflammatory protein 2. Neutrophil recruitment upon inflammatory challenge requires stimulation by microbiota through a myeloid differentiation primary response gene (88) (MyD88) -dependent pathway. MyD88 signalling is crucial during the development of the immune system but depending upon the ligand it may be dispensable at the time of the actual inflammatory challenge. Furthermore, pre-treatment of flora-deficient mice with a purified MyD88-pathway agonist is sufficient to restore neutrophil migration. In summary, this study provides insight into the role of gut microbiota in influencing acute inflammation at sites outside the gastrointestinal tract. PMID:23909393

  18. Metformin inhibits inflammatory response via AMPK-PTEN pathway in vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Ae [Department of Pharmacology, Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr [Department of Pharmacology, Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer PTEN was induced by metformin and inhibited by compound C and AMPK siRNA. Black-Right-Pointing-Pointer Metformin suppressed TNF-{alpha}-induced COX-2 and iNOS mRNA expression. Black-Right-Pointing-Pointer Compound C and bpv (pic) increased iNOS and COX-2 protein expression. Black-Right-Pointing-Pointer NF-{kappa}B activation was restored by inhibiting AMPK and PTEN. Black-Right-Pointing-Pointer AMPK and PTEN regulated TNF-{alpha}-induced ROS production in VSMCs. -- Abstract: Atherosclerosis is a chronic inflammation of the coronary arteries. Vascular smooth muscle cells (VSMCs) stimulated by cytokines and chemokines accelerate the inflammatory response and migrate to the injured endothelium during the progression of atherosclerosis. Activation of AMP activated protein kinase (AMPK), a key sensor maintaining metabolic homeostasis, suppresses the inflammatory response. However, how AMPK regulates the inflammatory response is poorly understood. To identify the mechanism of this response, we focused on phosphatase and tensin homolog (PTEN), which is a negative regulator of inflammation. We investigated that activation of AMPK-induced PTEN expression and suppression of the inflammatory response through the AMPK-PTEN pathway in VSMCs. We treated with the well-known AMPK activator metformin to induce PTEN expression. PTEN was induced by metformin (2 mM) and inhibited by compound C (10 {mu}M) and AMPK siRNA. Tumor necrosis factor-alpha (TNF-{alpha}) was used to induce inflammation. The inflammatory response was confirmed by cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) expression, and activation of nuclear factor (NF)-{kappa}B. Metformin suppressed COX-2 and iNOS mRNA and protein expression dose dependently. Treatment with compound C and bpv (pic) in the presence of metformin, iNOS and COX-2 protein expression increased. NF-{kappa}B activation decreased in response to metformin and was restored by inhibiting AMPK

  19. Bioinformatics analysis of the early inflammatory response in a rat thermal injury model

    Directory of Open Access Journals (Sweden)

    Berthiaume Francois

    2007-01-01

    Full Text Available Abstract Background Thermal injury is among the most severe forms of trauma and its effects are both local and systemic. Response to thermal injury includes cellular protection mechanisms, inflammation, hypermetabolism, prolonged catabolism, organ dysfunction and immuno-suppression. It has been hypothesized that gene expression patterns in the liver will change with severe burns, thus reflecting the role the liver plays in the response to burn injury. Characterizing the molecular fingerprint (i.e., expression profile of the inflammatory response resulting from burns may help elucidate the activated mechanisms and suggest new therapeutic intervention. In this paper we propose a novel integrated framework for analyzing time-series transcriptional data, with emphasis on the burn-induced response within the context of the rat animal model. Our analysis robustly identifies critical expression motifs, indicative of the dynamic evolution of the inflammatory response and we further propose a putative reconstruction of the associated transcription factor activities. Results Implementation of our algorithm on data obtained from an animal (rat burn injury study identified 281 genes corresponding to 4 unique profiles. Enrichment evaluation upon both gene ontologies and transcription factors, verifies the inflammation-specific character of the selections and the rationalization of the burn-induced inflammatory response. Conducting the transcription network reconstruction and analysis, we have identified transcription factors, including AHR, Octamer Binding Proteins, Kruppel-like Factors, and cell cycle regulators as being highly important to an organism's response to burn response. These transcription factors are notable due to their roles in pathways that play a part in the gross physiological response to burn such as changes in the immune response and inflammation. Conclusion Our results indicate that our novel selection/classification algorithm has been

  20. Reorganization of nuclear compartments of type A neurons of trigeminal ganglia in response to inflammatory injury of peripheral nerve endings.

    Science.gov (United States)

    Navascues, J; Casafont, I; Villagra, N T; Lafarga, M; Berciano, M T

    2004-07-01

    In this study we have taken advantage of the high nuclear responsiveness of type A sensory ganglia neurons to variations of cellular activity to investigate the reorganization and dynamics of nuclear compartments involved in transcription and RNA processing in response to neuronal injury. As experimental model we have used the inflammatory injury of the peripheral nerve endings induced by formalin injection in the areas of ophthalmic/maxillary nerve distribution. We have performed immunofluorescence and confocal laser microscopy analysis with specific antibodies for different nuclear compartments and ultrastructural analysis. The initial response to neuronal injury, within the 3 days post-injury, consisted of chromatin condensation, reduction in the expression level of acetylated histone H4, accumulation of perichromatin granules, reorganization of splicing factors in prominent nuclear speckles, reduction in the number of Cajal bodies and nucleolar alterations. These changes tended to revert by day 7 post-injury and are consistent with a transient inhibition of transcription and RNA processing. Moreover, we have observed an early and sustained expression of the transcription factor c-Jun. These results illustrate the transcription-dependent organization of nuclear compartments in type A trigeminal neurons and also support the importance of the nuclear response to axonal injury as a key component in the regenerative capacity of this neuronal population.

  1. Effects of Thymol and Carvacrol, Constituents of Thymus vulgaris L. Essential Oil, on the Inflammatory Response

    Science.gov (United States)

    Fachini-Queiroz, Fernanda Carolina; Kummer, Raquel; Estevão-Silva, Camila Fernanda; Carvalho, Maria Dalva de Barros; Cunha, Joice Maria; Grespan, Renata; Bersani-Amado, Ciomar Aparecida; Cuman, Roberto Kenji Nakamura

    2012-01-01

    Thyme (Thymus vulgaris L., Lamiaceae) is an aromatic and medicinal plant that has been used in folk medicine, phytopharmaceutical preparations, food preservatives, and as an aromatic ingredient. The effect of Thymus vulgaris essential oil (TEO) and its isolated constituents thymol and cavacrol (CVL) were studied in the following experimental models: ear edema, carrageenan-induced pleurisy, and chemotaxis in vitro. In the pleurisy model, TEO, CVL, and thymol significantly inhibited inflammatory edema. However, only TEO and CVL inhibited leukocyte migration. In the in vitro chemotaxis experiment, CVL inhibited leukocyte migration, whereas thymol exerted a potent chemoattractant effect. In the ear edema model, CVL (10 mg/ear), applied topically, reduced edema formation, exerting a topical anti-inflammatory effect. Thymol did not reduce edema formation but rather presented an irritative response, probably dependent on histamine and prostanoid release. Our data suggest that the antiinflammatory effects of TEO and CVL are attributable to the inhibition of inflammatory edema and leukocyte migration. PMID:22919415

  2. Role of glycogen synthase kinase-3 beta in the inflammatory response caused by bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Cortés-Vieyra Ricarda

    2012-06-01

    Full Text Available Abstract Glycogen synthase kinase 3β (GSK3β plays a fundamental role during the inflammatory response induced by bacteria. Depending on the pathogen and its virulence factors, the type of cell and probably the context in which the interaction between host cells and bacteria takes place, GSK3β may promote or inhibit inflammation. The goal of this review is to discuss recent findings on the role of the inhibition or activation of GSK3β and its modulation of the inflammatory signaling in monocytes/macrophages and epithelial cells at the transcriptional level, mainly through the regulation of nuclear factor-kappaB (NF-κB activity. Also included is a brief overview on the importance of GSK3 in non-inflammatory processes during bacterial infection.

  3. 5'-methylthioadenosine modulates the inflammatory response to endotoxin in mice and in rat hepatocytes.

    Science.gov (United States)

    Hevia, Henar; Varela-Rey, Marta; Corrales, Fernando J; Berasain, Carmen; Martínez-Chantar, María L; Latasa, M Ujue; Lu, Shelly C; Mato, José M; García-Trevijano, Elena R; Avila, Matías A

    2004-04-01

    5'-methylthioadenosine (MTA) is a nucleoside generated from S-adenosylmethionine (AdoMet) during polyamine synthesis. Recent evidence indicates that AdoMet modulates in vivo the production of inflammatory mediators. We have evaluated the anti-inflammatory properties of MTA in bacterial lipopolysaccharide (LPS) challenged mice, murine macrophage RAW 264.7 cells, and isolated rat hepatocytes treated with pro-inflammatory cytokines. MTA administration completely prevented LPS-induced lethality. The life-sparing effect of MTA was accompanied by the suppression of circulating tumor necrosis factor-alpha (TNF-alpha), inducible NO synthase (iNOS) expression, and by the stimulation of IL-10 synthesis. These responses to MTA were also observed in LPS-treated RAW 264.7 cells. MTA prevented the transcriptional activation of iNOS by pro-inflammatory cytokines in isolated hepatocytes, and the induction of cyclooxygenase 2 (COX2) in RAW 264.7 cells. MTA inhibited the activation of p38 mitogen-activated protein kinase (MAPK), c-jun phosphorylation, inhibitor kappa B alpha (IkappaBalpha) degradation, and nuclear factor kappaB (NFkappaB) activation, all of which are signaling pathways related to the generation of inflammatory mediators. These effects were independent of the metabolic conversion of MTA into AdoMet and the potential interaction of MTA with the cAMP signaling pathway, central to the anti-inflammatory actions of its structural analog adenosine. In conclusion, these observations demonstrate novel immunomodulatory properties for MTA that may be of value in the management of inflammatory diseases.

  4. Activation of Alveolar Macrophages after Plutonium Oxide Inhalation in Rats: Involvement in the Early Inflammatory Response

    Energy Technology Data Exchange (ETDEWEB)

    Van der Meeren, A.; Tourdes, F.; Gremy, O.; Grillon, G.; Abram, M.C.; Poncy, J.L.; Griffiths, N. [CEA, DSV, DRR, SRCA, Centre DAM Ile de France, F-91297 Bruyeres Le Chatel, Arpajon (France)

    2008-07-01

    Alveolar macrophages play an important role in the distribution, clearance and inflammatory reactions after particle inhalation, which may influence long-term events such as fibrosis and tumorigenesis. The objectives of the present study were to investigate the early inflammatory events after plutonium oxide inhalation in rats and involvement of alveolar macrophages. Lung changes were studied from 3 days to 3 months after inhalation of PuO{sub 2} or different isotopic compositions (70% or 97% {sup 239}Pu) and initial lung deposits (range 2.1 to 43.4 kBq/rat). Analyses of bronchoalveolar lavages showed early increases in the numbers of granulocytes, lymphocytes and multi-nucleated macrophages. The activation of macrophages was evaluated ex vivo by measurement of inflammatory mediator levels in culture supernatants. TNF-alpha and chemokine MCP-1, MIP-2 and CINC-1 production was elevated from 7 days after inhalation and remained so up to 3 months. In contrast, IL-1 beta, IL-6 and IL-10 production was unchanged. At 6 weeks, pulmonary macrophage numbers and activation state were increased as observed from an immunohistochemistry study of lung sections with anti-ED1. Similarly, histological analyses of lung sections also showed evidence of inflammatory responses. In conclusion, our results indicate early inflammatory changes in the lungs of PuO{sub 2}-contaminated animals and the involvement of macrophages in this process. A dose-effect relationship was observed between the amount of radionuclide inhaled or retained at the time of analysis and inflammatory mediator production by alveolar macrophages 14 days after exposure. For similar initial lung deposits, the inflammatory manifestation appears higher for 97% {sup 239}Pu than for 70% {sup 239}Pu. (authors)

  5. Sustainable bonuses: Sign of corporate responsibility or window dressing?

    NARCIS (Netherlands)

    Kolk, A.; Perego, P.

    2014-01-01

    Despite a strong plea for integrating sustainability goals into traditional corporate bonus schemes, a comprehensive implementation of these systems has been lacking until recently. This article explores four illustrative cases from the Netherlands, where several multinationals started to pioneer

  6. Technical Approach Determines Inflammatory Response after Surgical and Transcatheter Aortic Valve Replacement.

    Directory of Open Access Journals (Sweden)

    Gabor Erdoes

    Full Text Available To investigate the periprocedural inflammatory response in patients with isolated aortic valve stenosis undergoing surgical aortic valve replacement (SAVR or transcatheter aortic valve implantation (TAVI with different technical approaches.Patients were prospectively allocated to one of the following treatments: SAVR using conventional extracorporeal circulation (CECC, n = 47 or minimized extracorporeal circulation (MECC, n = 15, or TAVI using either transapical (TA, n = 15 or transfemoral (TF, n = 24 access. Exclusion criteria included infection, pre-procedural immunosuppressive or antibiotic drug therapy and emergency indications. We investigated interleukin (IL-6, IL-8, IL-10, human leukocyte antigen (HLA-DR, white blood cell count, high-sensitivity C-reactive protein (hs-CRP and soluble L-selectin (sCD62L levels before the procedure and at 4, 24, and 48 h after aortic valve replacement. Data are presented for group interaction (p-values for inter-group comparison as determined by the Greenhouse-Geisser correction.SAVR on CECC was associated with the highest levels of IL-8 and hs-CRP (p<0.017, and 0.007, respectively. SAVR on MECC showed the highest descent in levels of HLA-DR and sCD62L (both p<0.001 in the perioperative period. TA-TAVI showed increased intraprocedural concentration and the highest peak of IL-6 (p = 0.017. Significantly smaller changes in the inflammatory markers were observed in TF-TAVI.Surgical and interventional approaches to aortic valve replacement result in inflammatory modulation which differs according to the invasiveness of the procedure. As expected, extracorporeal circulation is associated with the most marked pro-inflammatory activation, whereas TF-TAVI emerges as the approach with the most attenuated inflammatory response. Factors such as the pre-treatment patient condition and the extent of myocardial injury also significantly affect inflammatory biomarker patterns. Accordingly, TA-TAVI is to be classified not

  7. Primary cilia modulate TLR4-mediated inflammatory responses in hippocampal neurons.

    Science.gov (United States)

    Baek, Hyunjung; Shin, Hyo Jung; Kim, Jwa-Jin; Shin, Nara; Kim, Sena; Yi, Min-Hee; Zhang, Enji; Hong, Jinpyo; Kang, Joon Won; Kim, Yonghyun; Kim, Cuk-Seong; Kim, Dong Woon

    2017-09-19

    The primary cilium is an organelle that can act as a master regulator of cellular signaling. Despite the presence of primary cilia in hippocampal neurons, their function is not fully understood. Recent studies have demonstrated that the primary cilium influences interleukin (IL)-1β-induced NF-κB signaling, ultimately mediating the inflammatory response. We, therefore, investigated ciliary function and NF-κB signaling in lipopolysaccharide (LPS)-induced neuroinflammation in conjunction with ciliary length analysis. Since TLR4/NF-κB signaling is a well-known inflammatory pathway, we measured ciliary length and inflammatory mediators in wild type (WT) and TLR4-/- mice injected with LPS. Next, to exclude the effects of microglial TLR4, we examined the ciliary length, ciliary components, inflammatory cytokine, and mediators in HT22 hippocampal neuronal cells. Primary ciliary length decreased in hippocampal pyramidal neurons after intracerebroventricular injection of LPS in WT mice, whereas it increased in TLR4-/- mice. LPS treatment decreased primary ciliary length, activated NF-κB signaling, and increased Cox2 and iNOS levels in HT22 hippocampal neurons. In contrast, silencing Kif3a, a key protein component of cilia, increased ARL13B ciliary protein levels and suppressed NF-κB signaling and expression of inflammatory mediators. These data suggest that LPS-induced NF-κB signaling and inflammatory mediator expression are modulated by cilia and that the blockade of primary cilium formation by Kif3a siRNA regulates TLR4-induced NF-κB signaling. We propose that primary cilia are critical for regulating NF-κB signaling events in neuroinflammation and in the innate immune response.

  8. Tumour-Derived Interleukin-1 Beta Induces Pro-inflammatory Response in Human Mesenchymal Stem Cells

    DEFF Research Database (Denmark)

    Alajez, Nehad M; Al-toub, Mashael; Almusa, Abdulaziz

    ’ secreted factors as represented by a panel of human cancer cell lines (breast (MCF7 and MDA-MB-231); prostate (PC-3); lung (NCI-H522); colon (HT-29) and head & neck (FaDu)) on the biological characteristics of MSCs. Background Over the past several years, significant amount of research has emerged......, the goal of this study was to assess the cellular and molecular changes in MSCs in response to secreted factors present in conditioned media (CM) from a panel of human tumor cell lines covering a spectrum of human cancers (Breast, Prostate, Lung, colon, and head and neck). Research Morphological changes...... with bipolar processes. In association with phenotypic changes, genome-wide gene expression and bioinformatics analysis revealed an enhanced pro-inflammatory response of those MSCs. Pharmacological inhibitions of FAK and MAPKK severely impaired the pro-inflammatory response of MSCs to tumor CM (~80-99%, and 55...

  9. ECM hydrogel coating mitigates the chronic inflammatory response to polypropylene mesh.

    Science.gov (United States)

    Faulk, Denver M; Londono, Ricardo; Wolf, Matthew T; Ranallo, Christian A; Carruthers, Christopher A; Wildemann, Justin D; Dearth, Christopher L; Badylak, Stephen F

    2014-10-01

    Polypropylene has been used as a surgical mesh material for several decades. This non-degradable synthetic polymer provides mechanical strength, a predictable host response, and its use has resulted in reduced recurrence rates for ventral hernia and pelvic organ prolapse. However, polypropylene and similar synthetic materials are associated with a chronic local tissue inflammatory response and dense fibrous tissue deposition. These outcomes have prompted variations in mesh design to minimize the surface area interface and increase integration with host tissue. In contrast, biologic scaffold materials composed of extracellular matrix (ECM) are rapidly degraded in-vivo and are associated with constructive tissue remodeling and minimal fibrosis. The objective of the present study was to assess the effects of an ECM hydrogel coating on the long-term host tissue response to polypropylene mesh in a rodent model of abdominal muscle injury. At 14 days post implantation, the ECM coated polypropylene mesh devices showed a decreased inflammatory response as characterized by the number and distribution of M1 macrophages (CD86+/CD68+) around mesh fibers when compared to the uncoated mesh devices. At 180 days the ECM coated polypropylene showed decreased density of collagen and amount of mature type I collagen deposited between mesh fibers when compared to the uncoated mesh devices. This study confirms and extends previous findings that an ECM coating mitigates the chronic inflammatory response and associated scar tissue deposition characteristic of polypropylene. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages.

    Directory of Open Access Journals (Sweden)

    Henrik Andersson

    Full Text Available Macrophages in the lung are the primary cells being infected by Mycobacterium tuberculosis (Mtb during the initial manifestation of tuberculosis. Since the adaptive immune response to Mtb is delayed, innate immune cells such as macrophages and neutrophils mount the early immune protection against this intracellular pathogen. Neutrophils are short-lived cells and removal of apoptotic cells by resident macrophages is a key event in the resolution of inflammation and tissue repair. Since anti-inflammatory activity is not compatible with effective immunity to intracellular pathogens, we therefore investigated how uptake of apoptotic neutrophils modulates the function of Mtb-activated human macrophages. We show that Mtb infection exerts a potent proinflammatory activation of human macrophages with enhanced gene activation and release of proinflammatory cytokines and that this response was augmented by apoptotic neutrophils. The enhanced macrophage response is linked to apoptotic neutrophil-driven activation of the NLRP3 inflammasome and subsequent IL-1β signalling. We also demonstrate that apoptotic neutrophils not only modulate the inflammatory response, but also enhance the capacity of infected macrophages to control intracellular growth of virulent Mtb. Taken together, these results suggest a novel role for apoptotic neutrophils in the modulation of the macrophage-dependent inflammatory response contributing to the early control of Mtb infection.

  11. Potential Use of Salivary Markers for Longitudinal Monitoring of Inflammatory Immune Responses to Vaccination

    Directory of Open Access Journals (Sweden)

    Pei Wen Lim

    2016-01-01

    Full Text Available Vaccination, designed to trigger a protective immune response against infection, is a trigger for mild inflammatory responses. Vaccination studies can address the question of inflammation initiation, levels, and resolution as well as its regulation for respective studied pathogens. Such studies largely based on analyzing the blood components including specific antibodies and cytokines were usually constrained by number of participants and volume of collected blood sample. Hence, blood-based studies may not be able to cover the full dynamic range of inflammation responses induced by vaccination. In this review, the potential of using saliva in addition to blood for studying the kinetics of inflammatory response studies was assessed. Saliva sampling is noninvasive and has a great potential to be used for studies aimed at analysing the magnitude, time course, and variance in immune responses, including inflammation after vaccination. Based on a literature survey of inflammatory biomarkers that can be determined in saliva and an analysis of how these biomarkers could help to understand the mechanisms and dynamics of immune reactivity and inflammation, we propose that the saliva-based approach might have potential to add substantial value to clinical studies, particularly in vulnerable populations such as infants, toddlers, and ill individuals.

  12. An LPS based method to stimulate the inflammatory response in growing rabbits

    Directory of Open Access Journals (Sweden)

    C. Knudsen

    2016-03-01

    Full Text Available Reliable indicators are needed to study the relationship between the inflammatory response of the growing rabbit and breeding factors such as feeding practices. A lipopolysaccharide (LPS stimulation of the inflammatory response is a valid model of bacterial infection in laboratory animals, but no data on the growing rabbit has yet been obtained. The aim of our study was to determine an adequate dose of LPS to inject in growing rabbits in order to elicit a measurable inflammatory response in terms of plasmatic TNF-α and rise in rectal temperature. Three trials were carried out in this study: 2 development trials, the first (n=18 testing 3 doses of LPS (2, 10, 50 μg/kg on the plasmatic TNF-α concentration at 90 and 180 min post injection, and the second trial (n=36 testing 4 doses of LPS (50, 75, 100 and 150 μg/kg on the TNF-α concentration 90 min post injection and the rectal temperature. The third trial was designed as an application of the method in a large number of animals (n=32 to study the effect of feed restriction and dietary increase in digestible fibre to starch ratio on the LPS inflammatory challenge response of growing rabbits. In development trials 1 and 2, animals had measurable TNF-α responses for doses higher than 10 μg/kg at 90 min post injection, with an increase in the number of responsive animals along with the dose. High variability was observed in TNF-α concentrations in responsive animals (coefficient of variation from 44 to 94%. Animals demonstrated an increase in rectal temperature for all doses injected in the range of 50-150 μg/kg from 90 min post injection with a peak at 180 min (ΔTr =1.9±0.7°C. Our observations led us to choose a dose of 100 μg/kg of LPS for our following studies, as the responses in terms of temperature and TNF-α were the most satisfactory. The application of our LPS injection protocol to our nutritional study enabled us to validate our protocol (ΔTr =1.1±0.7°C at 180 min and 15

  13. Wild skylarks seasonally modulate energy budgets but maintain energetically costly inflammatory immune responses throughout the annual cycle

    NARCIS (Netherlands)

    Hegemann, A.; Matson, K.D.; Versteegh, M.A.; Tieleman, B.I.

    2012-01-01

    A central hypothesis of ecological immunology is that immune defences are traded off against competing physiological and behavioural processes. During energetically demanding periods, birds are predicted to switch from expensive inflammatory responses to less costly immune responses. Acute phase

  14. Wild Skylarks Seasonally Modulate Energy Budgets but Maintain Energetically Costly Inflammatory Immune Responses throughout the Annual Cycle

    NARCIS (Netherlands)

    Hegemann, Arne; Matson, Kevin D.; Versteegh, Maaike A.; Tieleman, B. Irene

    2012-01-01

    A central hypothesis of ecological immunology is that immune defences are traded off against competing physiological and behavioural processes. During energetically demanding periods, birds are predicted to switch from expensive inflammatory responses to less costly immune responses. Acute phase

  15. Suppressive effects of methylthiouracil on polyphosphate-mediated vascular inflammatory responses.

    Science.gov (United States)

    Min, Gahee; Ku, Sae-Kwang; Jeong, Seongdo; Baek, Moon-Chang; Bae, Jong-Sup

    2016-12-01

    Drug repositioning is used to discover drug candidates to treat human diseases, through the application of drugs or compounds that are approved for the treatment of other diseases. This method can significantly reduce the time required and cost of discovering new drug candidates for human diseases. Previous studies have reported pro-inflammatory responses of endothelial cells to the release of polyphosphate (PolyP). In this study, we examined the anti-inflammatory responses and mechanisms of methylthiouracil (MTU), which is an antithyroid drug, and its effects on PolyP-induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behaviour of human neutrophils and vascular permeability were determined in PolyP-activated HUVECs and mice. MTU suppressed the PolyP-mediated vascular barrier permeability, up-regulation of inflammatory biomarkers, adhesion/migration of leucocytes, and activation and/or production of nuclear factor-κB, tumour necrosis factor-α and interleukin-6. Furthermore, MTU demonstrated protective effects on PolyP-mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of MTU on various systemic inflammatory diseases, such as sepsis or septic shock. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  16. Mitochondrial fragmentation in human macrophages attenuates palmitate-induced inflammatory responses.

    Science.gov (United States)

    Zezina, Ekaterina; Snodgrass, Ryan G; Schreiber, Yannick; Zukunft, Sven; Schürmann, Christoph; Heringdorf, Dagmar Meyer Zu; Geisslinger, Gerd; Fleming, Ingrid; Brandes, Ralf P; Brüne, Bernhard; Namgaladze, Dmitry

    2018-02-02

    Macrophages in adipose tissue contribute to inflammation and the development of insulin resistance in obesity. Exposure of macrophages to saturated fatty acids alters cell metabolism and activates pro-inflammatory signaling. How fatty acids influence macrophage mitochondrial dynamics is unclear. We investigated the mechanism of palmitate-induced mitochondrial fragmentation and its impact on inflammatory responses in primary human macrophages. Fatty acids, such as palmitate, caused mitochondrial fragmentation in human macrophages. Increased mitochondrial fragmentation was also observed in peritoneal macrophages from hyperlipidemic apolipoprotein E knockout mice. Fatty acid-induced mitochondrial fragmentation was independent of the fatty acid chain saturation and required dynamin-related protein 1 (DRP1). Mechanistically, mitochondrial fragmentation was regulated by incorporation of palmitate into mitochondrial phospholipids and their precursors. Palmitate-induced endoplasmic reticulum stress and loss of mitochondrial membrane potential did not contribute to mitochondrial fragmentation. Macrophages treated with palmitate maintained intact mitochondrial respiration and ATP levels. Pharmacological or genetic inhibition of DRP1 enhanced palmitate-induced mitochondrial ROS production, c-Jun phosphorylation, and inflammatory cytokine expression. Our results indicate that mitochondrial fragmentation is a protective mechanism attenuating inflammatory responses induced by palmitate in human macrophages. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Patterns of inflammatory responses and parasite tolerance vary with malaria transmission intensity.

    Science.gov (United States)

    Ademolue, Temitope W; Aniweh, Yaw; Kusi, Kwadwo A; Awandare, Gordon A

    2017-04-11

    In individuals living in malaria-endemic regions, parasitaemia thresholds for the onset of clinical symptoms vary with transmission intensity. The mechanisms that mediate this relationship are however, unclear. Since inflammatory responses to parasite infection contribute to the clinical manifestation of malaria, this study investigated inflammatory cytokine responses in children with malaria from areas of different transmission intensities (ranging from low to high). Blood samples were obtained from children confirmed with malaria at community hospitals in three areas with differing transmission intensities. Cytokine levels were assessed using the Luminex®-based magnetic bead array system, and levels were compared across sites using appropriate statistical tests. The relative contributions of age, gender, parasitaemia and transmission intensity on cytokine levels were investigated using multivariate regression analysis. Parasite density increased with increasing transmission intensity in children presenting to hospital with symptomatic malaria, indicating that the parasitaemia threshold for clinical malaria increases with increasing transmission intensity. Furthermore, levels of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), interleukin (IL)-1β, IL-2, IL-6, IL-8, and IL-12, decreased with increasing transmission intensity, and correlated significantly with parasitaemia levels in the low transmission area but not in high transmission areas. Similarly, levels of anti-inflammatory cytokines, including IL-4, IL-7, IL-10 and IL-13, decreased with increasing transmission intensity, with IL-10 showing strong correlation with parasitaemia levels in the low transmission area. Multiple linear regression analyses revealed that transmission intensity was a stronger predictor of cytokine levels than age, gender and parasitaemia. Taken together, the data demonstrate a strong relationship between the prevailing

  18. Comparison of inflammatory responses following robotic and open colorectal surgery: a prospective study.

    Science.gov (United States)

    Zawadzki, Marek; Krzystek-Korpacka, Malgorzata; Gamian, Andrzej; Witkiewicz, Wojciech

    2017-03-01

    Robotic colorectal surgery continues to rise in popularity, but there remains little evidence on the stress response following the procedure. The aim of this study was to evaluate the inflammatory response to robotic colorectal surgery and compare it with the response generated by open colorectal surgery. This was a prospective nonrandomized comparative study involving 61 patients with colorectal cancer. The evaluation of inflammatory response to either robotic or open colorectal surgery was expressed as changes in interleukin-1β, interleukin-1 receptor antagonist, interleukin-6, tumor necrosis factor-α, C-reactive protein, and procalcitonin during the first three postoperative days. Of the 61 patients, 33 underwent robotic colorectal surgery while 28 had open colorectal surgery. Groups were comparable with respect to age, sex, BMI, cancer stage, and type of resection. The relative increase of interleukin-1 receptor antagonist at 8 h postoperative, compared to baseline, was higher in the open group (P = 0.006). The decrease of interleukin-1 receptor antagonist on postoperative days 1 and 3, compared to the maximum at 8 h, was more pronounced in the open group than in the robotic group (P = 0.008, P = 0.006, respectively), and the relative increase of interleukin-6 at 8 h after incision was higher in the open group (P = 0.007). The relative increase of procalcitonin on postoperative days 1 and 3 was higher in the open group than the robotic group (P robotic colorectal surgery results in a less pronounced inflammatory response and more pronounced anti-inflammatory action.

  19. Obese mice exhibit an altered behavioural and inflammatory response to lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Catherine B. Lawrence

    2012-09-01

    Obesity is associated with an increase in the prevalence and severity of infections. Genetic animal models of obesity (ob/ob and db/db mice display altered centrally-mediated sickness behaviour in response to acute inflammatory stimuli such as lipopolysaccharide (LPS. However, the effect of diet-induced obesity (DIO on the anorectic and febrile response to LPS in mice is unknown. This study therefore determined how DIO and ob/ob mice respond to a systemic inflammatory challenge. C57BL/6 DIO and ob/ob mice, and their respective controls, were given an intraperitoneal (i.p. injection of LPS. Compared with controls, DIO and ob/ob mice exhibited an altered febrile response to LPS (100 μg/kg over 8 hours. LPS caused a greater and more prolonged anorexic effect in DIO compared with control mice and, in ob/ob mice, LPS induced a reduction in food intake and body weight earlier than it did in controls. These effects of LPS in obese mice were also seen after a fixed dose of LPS (5 μg. LPS (100 μg/kg induced Fos protein expression in several brain nuclei of control mice, with fewer Fos-positive cells observed in the brains of obese mice. An altered inflammatory response to LPS was also observed in obese mice compared with controls: changes in cytokine expression and release were detected in the plasma, spleen, liver and peritoneal macrophages in obese mice. In summary, DIO and ob/ob mice displayed an altered behavioural response and cytokine release to systemic inflammatory challenge. These findings could help explain why obese humans show increased sensitivity to infections.

  20. Pro- and anti-inflammatory responses are regulated simultaneously from the first moments of septic shock.

    Science.gov (United States)

    Tamayo, Eduardo; Fernández, Ana; Almansa, Raquel; Carrasco, Elena; Heredia, María; Lajo, Carmen; Goncalves, Lisbeth; Gómez-Herreras, Jose I; de Lejarazu, Raúl Ortiz; Bermejo-Martin, Jesus F

    2011-06-01

    The relationships between cytokine responses in septic shock are currently poorly understood. Some studies have pointed to a biphasic model, with an initial proinflammatory phase, followed by a reactive, anti-inflammatory response to explain the pathogenesis of the most severe form of sepsis. However, evidence for the coexistence of both responses has been found. In this study, the plasma levels of 17 cytokines and chemokines, in 20 patients with septic shock, 11 patients with systemic inflammatory response syndrome (SIRS), during the first 24 hours following diagnosis, and 10 healthy controls, were analyzed and compared. Patients with septic shock showed increased levels of IL-6, IL-8, MCP-1, MIP-1β, IFN-γ, GM-CSF and IL-10 compared to healthy controls. Patients with SIRS showed higher levels of IL-6, IL-8, MCP-1, MIP-1β, G-CSF and IL-10 than controls. Patients with septic shock showed higher levels of IL-8, GM-CSF, MIP-1β than those with SIRS. The Spearman test demonstrated a positive association between the pro-inflammatory mediators IL-6, IL-8, MCP-1, MIP-1β, IFN-γ, GM-CSF and the immunomodulatory cytokine IL-10 in septic shock. Consequently, correlation studies supported the notion that secretion of pro- and anti-inflammatory mediators in septic shock occurs as a simultaneous immune response program initiated early in the course of the disease, revealing that both types of cytokine play a role from the very beginning of this life-threatening condition.

  1. Eukaryotic-like Kinase Expression in Enterohemorrhagic Escherichia coli: Potential for Enhancing Host Aggressive Inflammatory Response.

    Science.gov (United States)

    Li, Tao; Li, Zhan; Chen, Fanghong; Liu, Xiong; Ning, Nianzhi; Huang, Jie; Wang, Hui

    2017-11-27

    Enterohemorrhagic Escherichia coli (EHEC) or other attaching/effacing pathogen infections often cause host intestinal inflammation and pathology, which is thought to result in part from a host aggressive innate immune response. However, few effectors that play an important role in this pathology change have been reported. In this study, we discovered a previously unknown EHEC effector, Stk (putative serine/threonine kinase), which induces host aggressive inflammatory response during EHEC infection. Interestingly, homologous proteins of Stk are widely distributed in many pathogens. After translocating into the infected host cells, Stk efficiently phosphorylates IκBα and activates the NF-κB pathway. In EHEC-infected mice, Stk increases serum keratinocyte-derived cytokine (KC) levels and hyperactivates the inflammatory response of the colon, intensifying pathological injury of the colon. The virulence of Stk is based on its eukaryotic-like kinase activity. In conclusion, our data suggest that Stk is a new effector that induces the host aggressive inflammatory response during EHEC infection. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  2. Stenotrophomonas maltophilia outer membrane vesicles elicit a potent inflammatory response in vitro and in vivo.

    Science.gov (United States)

    Kim, Yoo Jeong; Jeon, Hyejin; Na, Seok Hyeon; Kwon, Hyo Il; Selasi, Gati Noble; Nicholas, Asiimwe; Park, Tae In; Lee, Sang Hwa; Lee, Je Chul

    2016-11-01

    Stenotrophomonas maltophilia has become one of the most prevalent opportunistic pathogens in hospitalized patients. This microorganism secretes outer membrane vesicles (OMVs), but the pathogenesis of S. maltophilia as it relates to OMVs has not been characterized. This study investigated the cytotoxic activity of S. maltophilia OMVs and their ability to induce inflammatory responses both in vitro and in vivo Stenotrophomonas maltophilia ATCC 13637 and two clinical isolates were found to secrete spherical OMVs during in vitro culture. OMVs from S. maltophilia ATCC 13637 were cytotoxic to human lung epithelial A549 cells. Stenotrophomonas maltophilia OMVs stimulated the expression of proinflammatory cytokine and chemokine genes, including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α and monocyte chemoattractant protein-1, in A549 cells. Early inflammatory responses such as congestion and neutrophilic infiltrations and profound expression of proinflammatory cytokine and chemokine genes were observed in the lungs of mice injected with S. maltophilia OMVs, and were similar to responses elicited by the bacteria. Our data demonstrate that S. maltophilia OMVs are important secretory nanocomplexes that elicit a potent inflammatory response that might contribute to S. maltophilia pathogenesis during infection. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Global Analysis of Neutrophil Responses to Neisseria gonorrhoeae Reveals a Self-Propagating Inflammatory Program

    Science.gov (United States)

    Sintsova, Anna; Sarantis, Helen; Islam, Epshita A.; Sun, Chun Xiang; Amin, Mohsen; Chan, Carlos H. F.; Stanners, Clifford P.; Glogauer, Michael; Gray-Owen, Scott D.

    2014-01-01

    An overwhelming neutrophil-driven response causes both acute symptoms and the lasting sequelae that result from infection with Neisseria gonorrhoeae. Neutrophils undergo an aggressive opsonin-independent response to N. gonorrhoeae, driven by the innate decoy receptor CEACAM3. CEACAM3 is exclusively expressed by human neutrophils, and drives a potent binding, phagocytic engulfment and oxidative killing of Opa-expressing bacteria. In this study, we sought to explore the contribution of neutrophils to the pathogenic inflammatory process that typifies gonorrhea. Genome-wide microarray and biochemical profiling of gonococcal-infected neutrophils revealed that CEACAM3 engagement triggers a Syk-, PKCδ- and Tak1-dependent signaling cascade that results in the activation of an NF-κB-dependent transcriptional response, with consequent production of pro-inflammatory cytokines. Using an in vivo model of N. gonorrhoeae infection, we show that human CEACAM-expressing neutrophils have heightened migration toward the site of the infection where they may be further activated upon Opa-dependent binding. Together, this study establishes that the role of CEACAM3 is not restricted to the direct opsonin-independent killing by neutrophils, since it also drives the vigorous inflammatory response that typifies gonorrhea. By carrying the potential to mobilize increasing numbers of neutrophils, CEACAM3 thereby represents the tipping point between protective and pathogenic outcomes of N. gonorrhoeae infection. PMID:25188454

  4. Kinetics of the inflammatory response following intramuscular injection of aluminum adjuvant.

    Science.gov (United States)

    Lu, Fangjia; Hogenesch, Harm

    2013-08-20

    Aluminum-containing adjuvants are widely used in human and veterinary vaccines, but their mechanism of action is not well understood. Recent evidence suggests an important role for inflammation in the immune response to aluminum-adjuvanted vaccines. To better understand this process, vaccines with aluminum adjuvant were injected into naïve or previously immunized mice and the injection sites were characterized for the corresponding primary and secondary inflammatory response at different time points after immunization. Inflammatory cells appeared at the injection site between 2h and 6h after vaccination, dominated by neutrophils at first, followed by macrophages, and later eosinophils and MHCII(+) cells. The number of cells at the injection site increased over time, except neutrophils, which decreased in number after day 2. There was extensive phagocytosis of aluminum adjuvant particles by macrophages. In secondary immunized mice, a faster and more robust recruitment of eosinophils, macrophages, and antigen presenting cells was observed at the injection site. The enhanced recruitment of inflammatory cells in previously immunized mice coincided with increased expression of relevant chemokines at the injection site. Since neutrophils accumulated first in response to aluminum-adjuvanted vaccines, their role was evaluated by depleting them prior to vaccination. Neutrophil depletion transiently reduced the recruitment of macrophages but it did not change the recruitment of eosinophils and MHCII(+) cells or the quality and magnitude of the antibody response. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Inflammatory response to Porphyromonas gingivalis partially requires interferon regulatory factor (IRF) 3.

    Science.gov (United States)

    Shaik-Dasthagirisaheb, Yazdani B; Huang, Nasi; Gibson, Frank C

    2014-04-01

    Innate immune activation with expression of pro-inflammatory molecules such as TNF-α is a hallmark of the chronic inflammation associated with periodontal disease (PD). Porphyromonas gingivalis, a bacterium associated with PD, engages TLRs and activates MyD88-dependent and TIR-domain-containing adapter-inducing IFN-β (TRIF)-dependent signaling pathways. IFN regulatory factor (IRF) 3 is activated in a TRIF-dependent manner and participates in production of cytokines such as TNF-α; however, little is known regarding IRF3 and the host response to PD pathogens. We speculated that IRF3 participates in the host inflammatory response to P. gingivalis. Our results show that bone marrow macrophages (MØ) from WT mice respond to P. gingivalis with activation and nuclear translocation of IRF3. Compared with WT, MØ from IRF3(-/-), TRIF(-/-), and TLR4(-/-) mice responded with reduced levels of TNF-α on P. gingivalis challenge. In addition, full expression of IL-6 and RANTES by MØ to P. gingivalis was dependent on IRF3. Lastly, employing MØ from IRF3(-/-) and IRF7(-/-) mice we observed a significant role for IRF3 and a modest role for IRF7 in the P. gingivalis-elicited TNF-α response. These studies identify a role for IRF3 in the inflammatory response by MØ to the periodontal pathogen P. gingivalis.

  6. Differential inflammatory response to acrylonitrile in rat primary astrocytes and microglia.

    Science.gov (United States)

    Caito, Samuel W; Yu, Yingchun; Aschner, Michael

    2014-05-01

    Acrylonitrile (ACN) is extensively used in the production of plastics, resins, nitriles and other commercial products. Chronic low dose exposures to ACN cause glial cell tumors in rats, primarily microglial in origin. Recently it has been determined that astrocytes and microglia respond to ACN-induced oxidative stress differently, which may influence cell-specific activation of inflammatory and carcinogenic pathways. This study was conducted to compare the inflammatory responses of astrocytes and microglia following ACN treatment in vitro to further characterize differential sensitivities and adaptive responses in these cell types. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p53 levels were measured along with levels of 12 different cytokines and chemokines in primary rat microglia and astrocytes. Additionally levels of cytochrome P450 2E1 (CYP2E1) were measured to evaluate the cells' ability to metabolize ACN. Results indicate that while both cells upregulate p53 and NF-κB, the cytokines and chemokines produced differ between the cell types. Astrocytes, but not microglia, upregulated CYP2E1 in response to ACN, which may be due to the astrocytes accumulating more ACN than the microglia. Altogether our data implicate the inflammatory response as an important event in ACN-induced neurotoxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Aspergillus fumigatus Triggers Inflammatory Responses by Stage-Specific beta-Glucan Display.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available Inhalation of fungal spores (conidia occurs commonly and, in specific circumstances, can result in invasive disease. We investigated the murine inflammatory response to conidia of Aspergillus fumigatus, the most common invasive mold in immunocompromised hosts. In contrast to dormant spores, germinating conidia induce neutrophil recruitment to the airways and TNF-alpha/MIP-2 secretion by alveolar macrophages. Fungal beta-glucans act as a trigger for the induction of these inflammatory responses through their time-dependent exposure on the surface of germinating conidia. Dectin-1, an innate immune receptor that recognizes fungal beta-glucans, is recruited in vivo to alveolar macrophage phagosomes that have internalized conidia with exposed beta-glucans. Antibody-mediated blockade of Dectin-1 partially inhibits TNF-alpha/MIP-2 induction by metabolically active conidia. TLR-2- and MyD88-mediated signals provide an additive contribution to macrophage activation by germinating conidia. Selective responsiveness to germinating conidia provides the innate immune system with a mechanism to restrict inflammatory responses to metabolically active, potentially invasive fungal spores.

  8. Aspergillus fumigatus triggers inflammatory responses by stage-specific beta-glucan display.

    Directory of Open Access Journals (Sweden)

    Tobias M Hohl

    2005-11-01

    Full Text Available Inhalation of fungal spores (conidia occurs commonly and, in specific circumstances, can result in invasive disease. We investigated the murine inflammatory response to conidia of Aspergillus fumigatus, the most common invasive mold in immunocompromised hosts. In contrast to dormant spores, germinating conidia induce neutrophil recruitment to the airways and TNF-alpha/MIP-2 secretion by alveolar macrophages. Fungal beta-glucans act as a trigger for the induction of these inflammatory responses through their time-dependent exposure on the surface of germinating conidia. Dectin-1, an innate immune receptor that recognizes fungal beta-glucans, is recruited in vivo to alveolar macrophage phagosomes that have internalized conidia with exposed beta-glucans. Antibody-mediated blockade of Dectin-1 partially inhibits TNF-alpha/MIP-2 induction by metabolically active conidia. TLR-2- and MyD88-mediated signals provide an additive contribution to macrophage activation by germinating conidia. Selective responsiveness to germinating conidia provides the innate immune system with a mechanism to restrict inflammatory responses to metabolically active, potentially invasive fungal spores.

  9. Tobacco and e-cigarette products initiate Kupffer cell inflammatory responses.

    Science.gov (United States)

    Rubenstein, David A; Hom, Sarah; Ghebrehiwet, Berhane; Yin, Wei

    2015-10-01

    Kupffer cells are liver resident macrophages that are responsible for screening and clearing blood of pathogens and foreign particles. It has recently been shown that Kupffer cells interact with platelets, through an adhesion based mechanism, to aid in pathogen clearance and then these platelets re-enter the general systemic circulation. Thus, a mechanism has been identified that relates liver inflammation to possible changes in the systemic circulation. However, the role that Kupffer cells play in cardiovascular disease initiation/progression has not been elucidated. Thus, our objective was to determine whether or not Kupffer cells are responsive to a classical cardiovascular risk factor and if these changes can be transmitted into the general systemic circulation. If Kupffer cells initiate inflammatory responses after exposure to classical cardiovascular risk factors, then this provides a potential alternative/synergistic pathway for cardiovascular disease initiation. We aimed to elucidate the prevalence of this potential pathway. We hypothesized that Kupffer cells would initiate a robust inflammatory response after exposure to tobacco cigarette or e-cigarette products and that the inflammatory response would have the potential to antagonize other salient cells for cardiovascular disease progression. To test this, Kupffer cells were incubated with tobacco smoke extracts, e-cigarette vapor extracts or pure nicotine. Complement deposition onto Kupffer cells, Kupffer cell complement receptor expression, oxidative stress production, cytokine release and viability and density were assessed after the exposure. We observed a robust inflammatory response, oxidative stress production and cytokine release after Kupffer cells were exposed to tobacco or e-cigarette extracts. We also observed a marginal decrease in cell viability coupled with a significant decrease in cell density. In general, this was not a function of the extract formulation (e.g. tobacco vs. e

  10. Agent-based modeling of endotoxin-induced acute inflammatory response in human blood leukocytes.

    Directory of Open Access Journals (Sweden)

    Xu Dong

    2010-02-01

    Full Text Available Inflammation is a highly complex biological response evoked by many stimuli. A persistent challenge in modeling this dynamic process has been the (nonlinear nature of the response that precludes the single-variable assumption. Systems-based approaches offer a promising possibility for understanding inflammation in its homeostatic context. In order to study the underlying complexity of the acute inflammatory response, an agent-based framework is developed that models the emerging host response as the outcome of orchestrated interactions associated with intricate signaling cascades and intercellular immune system interactions.An agent-based modeling (ABM framework is proposed to study the nonlinear dynamics of acute human inflammation. The model is implemented using NetLogo software. Interacting agents involve either inflammation-specific molecules or cells essential for the propagation of the inflammatory reaction across the system. Spatial orientation of molecule interactions involved in signaling cascades coupled with the cellular heterogeneity are further taken into account. The proposed in silico model is evaluated through its ability to successfully reproduce a self-limited inflammatory response as well as a series of scenarios indicative of the nonlinear dynamics of the response. Such scenarios involve either a persistent (noninfectious response or innate immune tolerance and potentiation effects followed by perturbations in intracellular signaling molecules and cascades.The ABM framework developed in this study provides insight on the stochastic interactions of the mediators involved in the propagation of endotoxin signaling at the cellular response level. The simulation results are in accordance with our prior research effort associated with the development of deterministic human inflammation models that include transcriptional dynamics, signaling, and physiological components. The hypothetical scenarios explored in this study would

  11. Agent-based modeling of endotoxin-induced acute inflammatory response in human blood leukocytes.

    Science.gov (United States)

    Dong, Xu; Foteinou, Panagiota T; Calvano, Steven E; Lowry, Stephen F; Androulakis, Ioannis P

    2010-02-18

    Inflammation is a highly complex biological response evoked by many stimuli. A persistent challenge in modeling this dynamic process has been the (nonlinear) nature of the response that precludes the single-variable assumption. Systems-based approaches offer a promising possibility for understanding inflammation in its homeostatic context. In order to study the underlying complexity of the acute inflammatory response, an agent-based framework is developed that models the emerging host response as the outcome of orchestrated interactions associated with intricate signaling cascades and intercellular immune system interactions. An agent-based modeling (ABM) framework is proposed to study the nonlinear dynamics of acute human inflammation. The model is implemented using NetLogo software. Interacting agents involve either inflammation-specific molecules or cells essential for the propagation of the inflammatory reaction across the system. Spatial orientation of molecule interactions involved in signaling cascades coupled with the cellular heterogeneity are further taken into account. The proposed in silico model is evaluated through its ability to successfully reproduce a self-limited inflammatory response as well as a series of scenarios indicative of the nonlinear dynamics of the response. Such scenarios involve either a persistent (non)infectious response or innate immune tolerance and potentiation effects followed by perturbations in intracellular signaling molecules and cascades. The ABM framework developed in this study provides insight on the stochastic interactions of the mediators involved in the propagation of endotoxin signaling at the cellular response level. The simulation results are in accordance with our prior research effort associated with the development of deterministic human inflammation models that include transcriptional dynamics, signaling, and physiological components. The hypothetical scenarios explored in this study would potentially improve

  12. Faecal calprotectin assay after induction with anti-Tumour Necrosis Factor α agents in inflammatory bowel disease: Prediction of clinical response and mucosal healing at one year.

    Science.gov (United States)

    Guidi, Luisa; Marzo, Manuela; Andrisani, Gianluca; Felice, Carla; Pugliese, Daniela; Mocci, Giammarco; Nardone, Olga; De Vitis, Italo; Papa, Alfredo; Rapaccini, Gianlodovico; Forni, Franca; Armuzzi, Alessandro

    2014-11-01

    Faecal calprotectin levels correlate with inflammation in inflammatory bowel disease. We evaluated the role of faecal calprotectin after anti-Tumour Necrosis Factor α induction in inflammatory bowel disease patients to predict therapeutic effect at one year. Faecal calprotectin levels were measured in stools of 63 patients before and after induction of anti-Tumour Necrosis Factor α therapy. Clinical activity, measured by clinical indices, was assessed before and after biologic treatment. Clinical responders after induction were included in the study and colonoscopy was performed before and after one year of treatment to assess mucosal healing. 63 patients (44 Crohn's disease, 19 ulcerative colitis) were prospectively included (41.2% males, mean age at diagnosis 33 years). A sustained clinical response during the first year was observed in 57% of patients; median faecal calprotectin was 106 μg/g after induction versus 308 μg/g pre-induction (p<0.0001). Post-induction faecal calprotectin was significantly lower in responders versus non-responders (p=0.0002). Post-induction faecal calprotectin had 83% sensitivity and 74% specificity (cut-off ≤ 168 μg/g) for predicting a sustained clinical response at one year (p=0.0001); also, sensitivity was 79% and specificity 57% (cut-off ≤ 121 μg/g) for predicting mucosal healing (p=0.0001). In inflammatory bowel disease faecal calprotectin assay after anti-Tumour Necrosis Factor α induction can be used as a marker to predict sustained clinical response and mucosal healing at one year. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  13. Chasing Responsible Sourcing: The case of UK retailers and sustainable seafood

    OpenAIRE

    Chironna, Serena

    2016-01-01

    Responsible Sourcing is gaining growing importance for companies willing to demonstrate responsibility and commitment to sustainable practices. Sourcing is a key element of supply chain management and by adopting responsible sourcing practices, companies can greatly contribute to the sustainability of their entire supply chains. Being close to both customers and suppliers, retailers hold a particularly influential position in the supply chain and their sourcing choices can play a key role for...

  14. Reseña: Critical Studies on Corporate Responsibility, Governance and Sustainability, Vol. 4 y 6

    Directory of Open Access Journals (Sweden)

    Adrián Zicari

    2014-10-01

    Full Text Available Corporate Social Irresponsibility: A Challenging Concept. Series: Critical Studies on Corporate Responsibility, Governance and Sustainability, Vol. 4. Ralph Tench, William Sun and Brian Jones, 2012, Emerald Group Publishing Limited, 315 pages. Communicating Corporate Social Responsibility Perspectives and Practice. Series: Critical Studies on Corporate Responsibility, Governance and Sustainability, Vol. 6. Ralph Tench, William Sun and Brian Jones, 2014, Emerald Group Publishing Limited, 456 pages

  15. Importance of TLR2 on hepatic immune and non-immune cells to attenuate the strong inflammatory liver response during Trypanosoma cruzi acute infection.

    Directory of Open Access Journals (Sweden)

    Eugenio Antonio Carrera-Silva

    Full Text Available BACKGROUND: Toll-like receptors (TLR and cytokines play a central role in the pathogen clearance as well as in pathological processes. Recently, we reported that TLR2, TLR4 and TLR9 are differentially modulated in injured livers from BALB/c and C57BL/6 (B6 mice during Trypanosoma cruzi infection. However, the molecular and cellular mechanisms involved in local immune response remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we demonstrate that hepatic leukocytes from infected B6 mice produced higher amounts of pro-inflammatory cytokines than BALB/c mice, whereas IL10 and TGFβ were only released by hepatic leukocytes from BALB/c. Strikingly, a higher expression of TLR2 and TLR4 was observed in hepatocytes of infected BALB/c mice. However, in infected B6 mice, the strong pro-inflammatory response was associated with a high and sustained expression of TLR9 and iNOS in leukocytes and hepatic tissue respectively. Additionally, co-expression of gp91- and p47-phox NADPH oxidase subunits were detected in liver tissue of infected B6 mice. Notably, the pre-treatment previous to infection with Pam3CSK4, TLR2-agonist, induced a significant reduction of transaminase activity levels and inflammatory foci number in livers of infected B6 mice. Moreover, lower pro-inflammatory cytokines and increased TGFβ levels were detected in purified hepatic leukocytes from TLR2-agonist pre-treated B6 mice. CONCLUSIONS/SIGNIFICANCE: Our results describe some of the main injurious signals involved in liver immune response during the T. cruzi acute infection. Additionally we show that the administration of Pam3CSk4, previous to infection, can attenuate the exacerbated inflammatory response of livers in B6 mice. These results could be useful to understand and design novel immune strategies in controlling liver pathologies.

  16. Functional Roles of p38 Mitogen-Activated Protein Kinase in Macrophage-Mediated Inflammatory Responses

    Directory of Open Access Journals (Sweden)

    Yanyan Yang

    2014-01-01

    Full Text Available Inflammation is a natural host defensive process that is largely regulated by macrophages during the innate immune response. Mitogen-activated protein kinases (MAPKs are proline-directed serine and threonine protein kinases that regulate many physiological and pathophysiological cell responses. p38 MAPKs are key MAPKs involved in the production of inflammatory mediators, including tumor necrosis factor-α (TNF-α and cyclooxygenase-2 (COX-2. p38 MAPK signaling plays an essential role in regulating cellular processes, especially inflammation. In this paper, we summarize the characteristics of p38 signaling in macrophage-mediated inflammation. In addition, we discuss the potential of using inhibitors targeting p38 expression in macrophages to treat inflammatory diseases.

  17. Interactions between Intestinal Microbiota and Host Immune Response in Inflammatory Bowel Disease

    Science.gov (United States)

    Zhang, Ming; Sun, Kaiji; Wu, Yujun; Yang, Ying; Tso, Patrick; Wu, Zhenlong

    2017-01-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. Although the etiology and pathogenesis of IBD remain unclear, both genetic susceptibility and environmental factors are implicated in the initiation and progression of IBD. Recent studies with experimental animal models and clinical patients indicated that the intestinal microbiota is one of the critical environmental factors that influence nutrient metabolism, immune responses, and the health of the host in various intestinal diseases, including ulcerative colitis and Crohn’s disease. The objective of this review is to highlight the crosstalk between gut microbiota and host immune response and the contribution of this interaction to the pathogenesis of IBD. In addition, potential therapeutic strategies targeting the intestinal micro-ecosystem in IBD are discussed. PMID:28855901

  18. Strategies for modulating the inflammatory response after decompression from abdominal compartment syndrome

    Science.gov (United States)

    2012-01-01

    Background Management of the open abdomen is an increasingly common part of surgical practice. The purpose of this review is to examine the scientific background for the use of temporary abdominal closure (TAC) in the open abdomen as a way to modulate the local and systemic inflammatory response, with an emphasis on decompression after abdominal compartment syndrome (ACS). Methods A review of the relevant English language literature was conducted. Priority was placed on articles published within the last 5 years. Results/Conclusion Recent data from our group and others have begun to lay the foundation for the concept of TAC as a method to modulate the local and/or systemic inflammatory response in patients with an open abdomen resulting from ACS. PMID:22472164

  19. Effect of acupuncture intervention on the intestinal mucosal inflammatory response and immune response balance in animals with ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Meng-Fan Yang

    2017-07-01

    Full Text Available Objective: To study the effect of acupuncture intervention on the intestinal mucosal inflammatory response and immune response balance in animals with ulcerative colitis (UC. Methods: Adult, male SPF SD rats were selected and randomly divided into the control group, UC group and acupuncture group, and then the acupuncture intervention was established after the UC animal model was established. 14 d after intervention, the expression of inflammatory mediators and Th1/Th2/Th17/Treg cytokines in intestinal mucosa, and the levels of inflammatory mediators and Th1/Th2/Th17/Treg cytokines in serum were detected. Results: NF-kB, HMGB-1, TNF-α, IL-1β, IFN-γ and IL-17 mRNA expression in intestinal mucosa as well as HMGB-1, TNF-α, IL-1β, IFN-γ and IL-17 levels in serum of UC group were significantly higher than those of control group while IL-4, IL-5 and TGF-β1 mRNA expression in intestinal mucosa as well as IL-4, IL-5 and TGF-β1 levels in serum were significantly lower than those of control group; NF-kB, HMGB-1, TNF-α, IL-1β, IFN-γ and IL-17 mRNA expression in intestinal mucosa as well as HMGB-1, TNF-α, IL-1β, IFN-γ and IL-17 levels in serum of acupuncture group were significantly lower than those of UC group while IL-4, IL-5 and TGF-β1 mRNA expression in intestinal mucosa as well as IL-4, IL-5 and TGF-β1 levels in serum were significantly higher than those of UC group. Conclusions: Acupuncture intervention can regulate the intestinal mucosal inflammatory response and immune response of animals with ulcerative colitis.

  20. Knowledge, responsibility and ethics of sustainability in view of the global change

    OpenAIRE

    Ayestarán, Ignacio

    2010-01-01

    This article explores the interrelationship among scientificknowledge, ethical debates and the question of responsibility through sustainability thinking. In a globalising world which appears to be establishing itself, sustainability should form the basis for achieving a new ethics, shared on both a local and global scale. The sustainability culture should become an integral part in this process, in which the rights of future generations, of non-human species and global shared resources are t...

  1. Substance P ameliorates collagen II-induced arthritis in mice via suppression of the inflammatory response

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Hyun Sook [College of Medicine, East-West Medical Research Institute, Kyung Hee University, 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-702 (Korea, Republic of); Son, Youngsook, E-mail: ysson@khu.ac.kr [Graduate School of Biotechnology and Department of Genetic Engineering, College of Life Science, Kyung Hee University Global Campus, Seochun-dong, Kiheung-ku, Yong In 441-706 (Korea, Republic of)

    2014-10-10

    Highlights: • SP can increase IL-10 levels and reduce TNF-α and IL-17 levels in RA. • SP causes the increase in T{sub reg}, M2 macrophage, and MSCs in RA. • SP-induced immune suppression leads to the blockade of RA progression. • SP can be used as the therapeutics for autoimmune-related inflammatory diseases. - Abstract: Current rheumatoid arthritis (RA) therapies such as biologics inhibiting pathogenic cytokines substantially delay RA progression. However, patient responses to these agents are not always complete and long lasting. This study explored whether substance P (SP), an 11 amino acids long endogenous neuropeptide with the novel ability to mobilize mesenchymal stem cells (MSC) and modulate injury-mediated inflammation, can inhibit RA progression. SP efficacy was evaluated by paw swelling, clinical arthritis scoring, radiological analysis, histological analysis of cartilage destruction, and blood levels of tumor necrosis factor-alpha (TNF-α) interleukin (IL)-10, and IL-17 in vivo. SP treatment significantly reduced local inflammatory signs, mean arthritis scores, degradation of joint cartilage, and invasion of inflammatory cells into the synovial tissues. Moreover, the SP treatment markedly reduced the size of spleens enlarged by excessive inflammation in CIA, increased IL-10 levels, and decreased TNF-α and IL-17 levels. Mobilization of stem cells and induction of T{sub reg} and M2 type macrophages in the circulation were also increased by the SP treatment. These effect of SP might be associated with the suppression of inflammatory responses in RA and, furthermore, blockade of RA progression. Our results propose SP as a potential therapeutic for autoimmune-related inflammatory diseases.

  2. Intratracheal synthetic CpG oligodeoxynucleotide causes acute lung injury with systemic inflammatory response

    Directory of Open Access Journals (Sweden)

    Hasegawa Naoki

    2009-09-01

    Full Text Available Abstract Bacterial genome is characterized by frequent unmethylated cytosine-phosphate-guanine (CpG motifs. Deleterious effects can occur when synthetic oligodeoxynucleotides (ODN with unmethylated CpG dinucleotides (CpG-ODN are administered in a systemic fashion. We aimed to evaluate the effect of intratracheal CpG-ODN on lung inflammation and systemic inflammatory response. C57BL/6J mice received intratracheal administration of CpG-ODN (0.01, 0.1, 1.0, 10, or 100 μM or control ODN without CpG motif. Bronchoalveolar lavage (BAL fluid was obtained 3 or 6 h or 1, 2, 7, or 14 days after the instillation and subjected to a differential cell count and cytokine measurement. Lung permeability was evaluated as the BAL fluid-to-plasma ratio of the concentration of human serum albumin that was injected 1 h before euthanasia. Nuclear factor (NF-κB DNA binding activity was also evaluated in lung homogenates. Intratracheal administration of 10 μM or higher concentration of CpG-ODN induced significant inflammatory cell accumulation into the airspace. The peak accumulation of neutrophils and lymphocytes occurred 1 and 2 days after the CpG-ODN administration, respectively. Lung permeability was increased 1 day after the 10 μM CpG-ODN challenge. CpG-ODN also induced nuclear translocation of NF-κB and upregulation of various inflammatory cytokines in BAL fluid and plasma. Histopathology of the lungs and liver revealed acute lung injury and liver damage with necrosis, respectively. Control ODN without CpG motif did not induce any inflammatory change. Since intratracheal CpG-ODN induced acute lung injury as well as systemic inflammatory response, therapeutic strategies to neutralize bacterial DNA that is released after administration of bactericidal agents should be considered.

  3. Histamine Induces Bovine Rumen Epithelial Cell Inflammatory Response via NF-κB Pathway

    Directory of Open Access Journals (Sweden)

    Xudong Sun

    2017-06-01

    Full Text Available Background/Aims: Subacute ruminal acidosis (SARA is a common disease in high-producing lactating cows. Rumenitis is the initial insult of SARA and is associated with the high concentrations of histamine produced in the rumen of dairy cows during SARA. However, the exact mechanism remains unclear. The objective of the current study is to investigate whether histamine induces inflammation of rumen epithelial cells and the underlying mechanism of this process. Methods: Bovine rumen epithelial cells were cultured and treated with different concentrations of histamine and pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor cultured in different pH medium (pH 7.2 or 5.5. qRT-PCR, Western-blotting, ELISA and immunocytofluorescence were used to evaluate whether histamine activated the NF-κB pathway and inflammatory cytokines. Results: The results showed that histamine significantly increased the activity of IKK β and the phosphorylation levels of IκB α, as well as upregulated the mRNA and protein expression levels of NF-κB p65 in the rumen epithelial cells cultured in neutral (pH=7.2 and acidic (pH=5.5 medium. Furthermore, histamine treatment also significantly increased the transcriptional activity of NF-κB p65. High expression and transcriptional activity of NF-κB p65 significantly increased the mRNA expressions and concentrations of inflammatory cytokines, tumor necrosis factor alpha (TNF-α, interleukin 6 (IL-6 and interleukin 1 beta (IL-1β, thereby inducing the inflammatory response in bovine rumen epithelial cells. However, inhibition of NF-κB p65 by PDTC significantly decreased the expressions and concentrations of the inflammatory cytokines induced by histamine in the rumen epithelial cells cultured in the neutral and acidic medium. Conclusion: The present data indicate that histamine induces the inflammatory response of bovine rumen epithelial cells through the NF-κB pathway.

  4. The mast cell integrates the splanchnic and systemic inflammatory response in portal hypertension

    Directory of Open Access Journals (Sweden)

    Arias Jorge-Luis

    2007-09-01

    Full Text Available Abstract Portal hypertension is a clinical syndrome that is difficult to study in an isolated manner since it is always associated with a greater or lesser degree of liver functional impairment. The aim of this review is to integrate the complications related to chronic liver disease by using both, the array of mast cell functions and mediators, since they possibly are involved in the pathophysiological mechanisms of these complications. The portal vein ligated rat is the experimental model most widely used to study this syndrome and it has been considered that a systemic inflammatory response is produced. This response is mediated among other inflammatory cells by mast cells and it evolves in three linked pathological functional systems. The nervous functional system presents ischemia-reperfusion and edema (oxidative stress and would be responsible for hyperdynamic circulation; the immune functional system causes tissue infiltration by inflammatory cells, particularly mast cells and bacteria (enzymatic stress and the endocrine functional system presents endothelial proliferation (antioxidative and antienzymatic stress and angiogenesis. Mast cells could develop a key role in the expression of these three phenotypes because their mediators have the ability to produce all the aforementioned alterations, both at the splanchnic level (portal hypertensive enteropathy, mesenteric adenitis, liver steatosis and the systemic level (portal hypertensive encephalopathy. This hypothetical splanchnic and systemic inflammatory response would be aggravated during the progression of the chronic liver disease, since the antioxidant ability of the body decreases. Thus, a critical state is produced, in which the appearance of noxious factors would favor the development of a dedifferentiation process protagonized by the nervous functional system. This system rapidly induces an ischemia-reperfusion phenotype with hydration and salinization of the body (hepatorenal

  5. Dietary supplementation of glycine modulates inflammatory response indicators in broiler chickens.

    Science.gov (United States)

    Takahashi, Kazuaki; Aoki, Akira; Takimoto, Testuya; Akiba, Yukio

    2008-11-01

    Three experiments were conducted to investigate the effect of dietary glycine (Gly) supplementation on inflammatory responses in broiler chicks fed a basal diet using maize and soybean meal as the primary ingredients. Inflammation-related processes following lipopolysaccharide (LPS) injection were examined by analysing plasma concentrations of nitrate plus nitrite (NOx) and ceruloplasmin (Cer) in experiments 1 and 2, or expression of several genes in the spleen and liver including IL-1 beta and -6, TNF-like ligand (TL)1A, inducible NO synthase, interferon (IFN)-gamma and toll-like receptor (TLR) 4 were examined in experiment 3. Growth performance was also determined following immunological stimulation by both LPS and Sephadex injection in experiment 2. In experiment 1, birds fed a diet supplemented with Gly at 10 or 20 g/kg showed lower responses in plasma NOx and Cer than birds fed the diet supplemented with Gly at 0 or 40 g/kg. In experiment 2, a similar effect of Gly supplementation at 10 g/kg on plasma NOx and Cer was observed when chicks were fed either an isonitrogenous diet with Gly or glutamic acid (Glu). Gly-supplemented diet-fed birds showed better growth performance than Glu-supplemented diet-fed birds. The splenic expression of inflammatory response-related genes in birds fed a diet supplemented with Gly at 10 g/kg diet was lower than that of birds fed the basal diet in experiment 3. These results suggest that dietary Gly supplementation modulates the inflammatory response partly through changes in the expression of pro-inflammatory cytokines such as IL-1, IL-6, IFN-gamma and TL1A.

  6. Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin

    Energy Technology Data Exchange (ETDEWEB)

    Tilton, Susan C., E-mail: susan.tilton@pnnl.gov [Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Waters, Katrina M.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Zangar, Richard C. [Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Lee, K. Monica [Battelle Toxicology Northwest, Richland, WA 99352 (United States); Bigelow, Diana J.; Pounds, Joel G.; Corley, Richard A. [Pacific Northwest National Laboratory, Richland, WA 99352 (United States)

    2013-03-01

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures. - Highlights: ► Obesity modulates inflammatory markers in BAL fluid after LPS exposure. ► Obese animals have a unique transcriptional signature in lung after LPS exposure. ► Obesity elevates inflammatory stress and reduces antioxidant capacity in the lung

  7. Cerebral inflammatory response and predictors of admission clinical grade after aneurysmal subarachnoid hemorrhage

    OpenAIRE

    Hanafy, Khalid A.; Stuart, R. Morgan; Fernandez, Luis; Schmidt, J. Michael; Claassen, Jan; Lee, Kiwon; Connolly, E. Sander; Mayer, Stephan A.; Badjatia, Neeraj

    2009-01-01

    Poor admission clinical grade is the most important determinant of outcome after aneurysmal subarachnoid hemorrhage (aSAH); however, little attention has been focused on independent predictors of poor admission clinical grade. We hypothesized that the cerebral inflammatory response initiated at the time of aneurysm rupture contributes to ultra-early brain injury and poor admission clinical grade. We sought to identify factors known to contribute to cerebral inflammation as well as markers of ...

  8. Inflammatory response in chronic degenerative endometritis mares treated with platelet-rich plasma.

    Science.gov (United States)

    Reghini, Maria Fernanda S; Ramires Neto, Carlos; Segabinazzi, Lorenzo G; Castro Chaves, Maria Manoela B; Dell'Aqua, Camila de Paula F; Bussiere, Maria Clara C; Dell'Aqua, José Antonio; Papa, Frederico O; Alvarenga, Marco Antonio

    2016-07-15

    Degenerative changes of the endometrium are directly related to age and fertility in mares. Chronic degenerative endometritis (CDE) is correlated with uterine fluid retention and reduced ability to clear uterine inflammation. Recent research in the areas of equine surgery and sports medicine has shown that platelet-rich plasma (PRP) treatment acts as an immunomodulator of the inflammatory response. Therefore, the aim of this study was to determine if the uterine infusion of PRP could modulate the local inflammatory response and modify the intrauterine NO concentrations after artificial insemination (AI) in both normal mares and those with CDE. Thirteen mares with endometrium classified as grade III on the histology (mares with CDE) and eight mares with endometrial histological classification I or II-a normal mares were selected to investigate the effect of PRP therapy. The mares were inseminated with fresh semen in two consecutive cycles in a crossover study design. Thereby, each mare served as its own control and the treatment was performed with intrauterine PRP infusion four hours after AI. The percentage of neutrophils in uterine cytology (CIT, %), uterine fluid accumulation observed on ultrasonography (FLU, mm) and nitric oxide concentration of uterine fluid (NO, μM) were analyzed before and 24 hours after AI. The results reported that mares with CDE (CIT, 68.3 ± 3.27, FLU, 10.7 ± 1.61) have a higher (P  0.05) between categories of mares. In treated cycles with PRP, the intrauterine inflammatory response decrease (P PRP was effective in modulating the exacerbated uterine inflammatory response to semen in mares with CDE but did not reduce NO concentrations in intrauterine fluid. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Sustainable occupational responses to climate change through lifestyle choices.

    Science.gov (United States)

    Hocking, Clare; Kroksmark, Ulla

    2013-03-01

    Abstract Occupational therapists and occupational scientists are increasingly aware of the relationship between occupation and global climate change, with some working to raise awareness of the issues and others proposing that an occupational perspective can make a valuable contribution to understanding and addressing the issues. In this discussion paper the United Nations Global Survey on Sustainable Lifestyles ( 1 ), which reports young adults' beliefs about everyday occupations that have a substantial impact on the environment (food, housekeeping, and transportation) is introduced. The authors argue that the survey findings are a valuable resource for occupational therapists who are concerned about global climate change and work with young adults (age 18-35), providing valuable insights into their concerns and preferences in relation to sustainability. To illustrate the insights contained in the reports, findings from four countries are presented: New Zealand and Sweden, the authors' countries of origin, and the Philippines and Lebanon which have people living in New Zealand and Sweden. Application to individual and community-based interventions to promote more sustainable lifestyles is suggested, along with studies to examine the perspectives of young adults with a disability, as their concerns and sustainability preferences might differ due to the barriers that limit their participation in educational and vocational occupations.

  10. Responsible and Sustainable Tourism : Strengthening Small-Scale ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Women in the developing world continue to face obstacles that limit their ability to establish careers and become leaders in the fields of science, technology, engineering, and mathematics ... Itzama Project : Sustainable Indigenous Development based on the Ethnobotanical Garden and Traditional Medicine Concept.

  11. HIF-1α expression in keloid and its correlation with angiogenesis, inflammatory response and apoptosis

    Directory of Open Access Journals (Sweden)

    Fei-Lun Ye

    2017-09-01

    Full Text Available Objective: To study the expression of hypoxia-inducible factor-1α (HIF-1α in keloid and its correlation with angiogenesis, inflammatory response and apoptosis. Methods: Keloid samples removed in the Third People’s Hospital of Chengdu between June 2014 and March 2017 were selected as the pathology group of the research, and normal skin tissues removed in the Third People’s Hospital of Chengdu due to injury were selected as the control group of the research. The expression of HIF-1α, angiogenesis molecules, inflammatory response cytokines and apoptosis molecules in keloid samples normal skin tissues were detected. Results: HIF- 1α, VEGF165, Flt-1, Flk-1, Ang-1, Tie-2, PGE2, PGF2α, MIF, Livin and Survivin mRNA expression in keloid of pathology group were significantly higher than those in normal skin tissue of control group while TSG-6, Caspase-3, Caspase-7 and Caspase-9 mRNA expression were significantly lower than those in normal skin tissue of control group; HIF-1α mRNA expression was positively correlated with VEGF165, Flt-1, Flk-1, Ang-1, Tie-2, PGE2, PGF2α, MIF, Livin and Survivin mRNA expression, and negatively correlated with TSG-6, Caspase-3, Caspase-7 and Caspase-9 mRNA expression. Conclusion: HIF-1α is highly expressed in keloid and can promote angiogenesis and inflammatory response and inhibit apoptosis.

  12. Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

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    Maes Michael

    2012-06-01

    Full Text Available Abstract It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia, physio-somatic (fatigue, hyperalgesia, malaise, anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuroinflammation and (neurodegenerative processes following less well defined triggers.

  13. Time-course evaluation and treatment of skin inflammatory immune response after ultraviolet B irradiation.

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    Paz, Mariela L; Ferrari, Alejandro; Weill, Federico S; Leoni, Juliana; Maglio, Daniel H Gonzalez

    2008-10-01

    Skin exposure to high doses of ultraviolet B (UVB) radiation generates a severe inflammatory skin response. In the present study we aim to investigate, using in vitro and in vivo models, the time-course of the inflammatory skin immune response after an acute exposure to UVB irradiation, as well as its modulation by a topical non-steroidal anti-inflammatory drug (NSAID) treatment, naproxen. PGE2 production and TNF-alpha levels increase in a post-irradiation time-dependent manner both in vivo and in vitro. This production pattern is also reflected in the iNOS expression levels in vivo and in the IL-6 levels in vitro. Changes observed in these mediators are correlated with histological alterations and dermal infiltration after the acute UVB irradiation. Naproxen treatment notably reduces PGE2 production and iNOS expression, reflecting the COX-NOS crosstalk already reported, although it causes an important increment in TNF-alpha synthesis in the epidermis of irradiated mice. Taken together, our data indicates that the epidermis is severely damaged by UVB radiation but then it is able to fully recover, and that the immune response is modulated by the NSAID treatment, since it is able to reduce the levels of some mediators as well as it can increase others.

  14. Equine colostral carbohydrates reduce lipopolysaccharide-induced inflammatory responses in equine peripheral blood mononuclear cells.

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    Vendrig, J C; Coffeng, L E; Fink-Gremmels, J

    2012-12-01

    Increasing evidence suggests that reactions to lipopolysaccharide (LPS), particularly in the gut, can be partly or completely mitigated by colostrum- and milk-derived oligosaccharides. Confirmation of this hypothesis could lead to the development of new therapeutic concepts. To demonstrate the influence of equine colostral carbohydrates on the inflammatory response in an in vitro model with equine peripheral blood mononuclear cells (PBMCs). Carbohydrates were extracted from mare colostrum, and then evaluated for their influence on LPS-induced inflammatory responses in PBMCs isolated from the same mares, mRNA expression of tumour necrosis factor-alpha, interleukin-6 and interleukin-10 was measured as well as the protein levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10). Equine colostral carbohydrates significantly reduced LPS-induced TNF-alpha protein at both times measured and significantly reduced LPS-induced TNF-alpha, IL-6 and IL-10 mRNA expression by PBMCs. Moreover, cell viability significantly increased in the presence of high concentrations of colostral carbohydrates. Carbohydrates derived from equine colostrum reduce LPS-induced inflammatory responses of equine PBMCs. Colostrum and milk-derived carbohydrates are promising candidates for new concepts in preventive and regenerative medicine.

  15. PKC activation induces inflammatory response and cell death in human bronchial epithelial cells.

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    Hyunhee Kim

    Full Text Available A variety of airborne pathogens can induce inflammatory responses in airway epithelial cells, which is a crucial component of host defence. However, excessive inflammatory responses and chronic inflammation also contribute to different diseases of the respiratory system. We hypothesized that the activation of protein kinase C (PKC is one of the essential mechanisms of inflammatory response in airway epithelial cells. In the present study, we stimulated human bronchial lung epithelial (BEAS-2B cells with the phorbol ester Phorbol 12, 13-dibutyrate (PDBu, and examined gene expression profile using microarrays. Microarray analysis suggests that PKC activation induced dramatic changes in gene expression related to multiple cellular functions. The top two interaction networks generated from these changes were centered on NFκB and TNF-α, which are two commonly known pathways for cell death and inflammation. Subsequent tests confirmed the decrease in cell viability and an increase in the production of various cytokines. Interestingly, each of the increased cytokines was differentially regulated at mRNA and/or protein levels by different sub-classes of PKC isozymes. We conclude that pathological cell death and cytokine production in airway epithelial cells in various situations may be mediated through PKC related signaling pathways. These findings suggest that PKCs can be new targets for treatment of lung diseases.

  16. Suppressive effects of lysozyme on polyphosphate-mediated vascular inflammatory responses

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Jiwoo [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566 (Korea, Republic of); Ku, Sae-Kwang [Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610 (Korea, Republic of); Lee, Suyeon [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566 (Korea, Republic of); Bae, Jong-Sup, E-mail: baejs@knu.ac.kr [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566 (Korea, Republic of)

    2016-06-10

    Lysozyme, found in relatively high concentration in blood, saliva, tears, and milk, protects us from the ever-present danger of bacterial infection. Previous studies have reported proinflammatory responses of endothelial cells to the release of polyphosphate(PolyP). In this study, we examined the anti-inflammatory responses and mechanisms of lysozyme and its effects on PolyP-induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behavior of human neutrophils, and vascular permeability were determined in PolyP-activated HUVECs and mice. Lysozyme suppressed the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/or production of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6. Furthermore, lysozyme demonstrated protective effects on PolyP-mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of lysozyme on various systemic inflammatory diseases, such as sepsis or septic shock. -- Highlights: •PolyP is shown to be an important mediator of vascular inflammation. •Lysozyme inhibited PolyP-mediated hyperpermeability. •Lysozyme inhibited PolyP-mediated septic response. •Lysozyme reduced PolyP-induced septic mortality.

  17. A prospective randomized study of the inflammatory responses to multiport and singleport laparoscopic hysterectomies.

    Science.gov (United States)

    Tormena, Renata Assef; Ribeiro, Sérgio Conti; Soares, José Maria; Maciel, Gustavo Arantes Rosa; Baracat, Edmund Chada

    2017-07-01

    To evaluate the inflammatory responses induced by laparoscopic hysterectomies with multiport and singleport approaches. This was a pilot prospective randomized study that included 42 women candidates for hysterectomy at School of Medicine, Hospital das Clínicas, USP. The patients were randomized to two groups: MP-TLH (total laparoscopic hysterectomy with 3 abdominal incisions), and SP-TLH (total laparoscopic hysterectomy with a single umbilical incision).We evaluated the inflammatory response (via CRP, IL-6, IL-10, TNFα, VEGF and leukogram assessments), surgical time, postoperative pain, blood loss and surgical complications in both groups. Both techniques were similar regarding C-reactive protein (p=.666), IL-6 (p=.833), IL-10 (p=.420), TNF-α(p=.098), VEGF (p=.092) and the leukogram (p=.712) measures. The operative time was significantly longer in the SP-TLH group than in the MP-TLH group (p=.001). The pain evaluation was similar in both groups (p=.170). Hemoglobin variation and the aspirated blood volume were similar in both groups (p=.493 and p=.347). There were no major complications. Multiport and singleport laparoscopic approaches are both safe methods for hysterectomy. Although SP-TLH resulted in a significantly longer operative time than MP-TLH, no differences were observed between the groups in inflammatory responses, blood loss and postoperative pain.

  18. Nonsteroidal anti-inflammatory drugs may affect cytokine response and benefit healing of combat-related extremity wounds.

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    Lisboa, Felipe A; Bradley, Matthew J; Hueman, Matthew T; Schobel, Seth A; Gaucher, Beverly J; Styrmisdottir, Edda L; Potter, Benjamin K; Forsberg, Jonathan A; Elster, Eric A

    2017-04-01

    After adequate operative debridement and antimicrobial therapies, combat-related extremity wounds that either heal or fail are both associated with a distinct inflammatory response. Short-term use of nonsteroidal anti-inflammatory drugs in postoperative pain management may affect this response and, by consequence, the healing potential of these wounds. We investigated whether patients treated with nonsteroidal anti-inflammatory drugs had a distinct inflammatory response; different rates of critical colonization, defined as >105 colony forming units on quantitative bacteriology; and healing potential. We retrospectively reviewed the records of 73 patients with combat-related extremity wounds. Patients were separated into 2 groups: those who received nonsteroidal anti-inflammatory drugs during the debridement period (nonsteroidal anti-inflammatory drugs group, N = 17) and those who did not (control group; N = 56). Serum and wound tissue samples collected during each operative debridement were measured for 32 known cytokines and tested for quantitative bacteriology, respectively. We compared cytokine concentrations between groups and then designed a logistic regression model to identify variables associated with successful wound healing, while controlling for known confounders. Despite similar demographics and wound characteristics, the nonsteroidal anti-inflammatory drugs group had significant lesser concentrations of inflammatory cytokines, interleukin-2, interleukin-6, interleukin-8, and monocyte chemoattractant protein-1. On multivariate analysis, nonsteroidal anti-inflammatory drug treatment emerged as a predictor of successful wound healing after controlling for known confounders such as wound size, tobacco use, Acute Physiology and Chronic Health Evaluation II score, and critical colonization. Treatment with nonsteroidal anti-inflammatory drugs for postoperative pain management after major combat-related extremity trauma is associated with lesser

  19. The role of oxidative stress and inflammatory response in the pathogenesis of mastitis in dairy cows

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    Nino Maćešić

    2017-01-01

    Full Text Available Mastitis is one of the most frequent diseases of dairy cows throughout the world, therefore it causes the greatest economic losses in dairy cattle industry. These losses are reflected through: reduced milk production, increased costs of medication and the other animal health services, reduced fertility, early culling of animals and the value of discarded milk. Mastitis is also important from the aspects of public health, milk processing and animal welfare. In the pathogenesis of mastitis the key role plays the innate immune response which is the first line of defence against the pathogen invasion of the udder. The innate immune response generates an inflammatory reaction which is the elementary response of an organism to the tissue trauma induced by any physical, chemical or biological causative agent, but primarily it is the protective mechanism of a vital significance which includes increased phagocytic activity, secretion of antimicrobial substances, fibrosis as well as the alterations in tissue structure of affected organ or body cavity. The release of a number of inflammatory mediators as well as reactive oxygen species (ROS is an important part of inflammatory response. In dairy cows, the metabolic challenge that occurred during the transition from dry period to early lactation may additionally increase the release of ROS which may contribute to development of oxidative stress and inflammatory response. Oxidative stress is defined as a shift in the balance from cellular oxidation-reduction reactions towards oxidation, i.e. to the state of excessive release of oxidants when their removal by antioxidants is impaired and even insufficient. During peripartum period antioxidantive status of dairy cows is seriously impaired and consequently both the oxidative stress and inflammatory response may present the predisposing factors to their higher susceptibility to intramammary infections (IMI and mastitis. This association between oxidative stress

  20. The role of oxidative stress and inflammatory response in the pathogenesis of mastitis in dairy cows

    Directory of Open Access Journals (Sweden)

    Romana Turk

    2017-04-01

    Full Text Available Mastitis is one of the most frequent diseases of dairy cows throughout the world, therefore it causes the greatest economic losses in dairy cattle industry. These losses are reflected through: reduced milk production, increased costs of medication and the other animal health services, reduced fertility, early culling of animals and the value of discarded milk. Mastitis is also important from the aspects of public health, milk processing and animal welfare. In the pathogenesis of mastitis the key role plays the innate immune response which is the first line of defence against the pathogen invasion of the udder. The innate immune response generates an inflammatory reaction which is the elementary response of an organism to the tissue trauma induced by any physical, chemical or biological causative agent, but primarily it is the protective mechanism of a vital significance which includes increased phagocytic activity, secretion of antimicrobial substances, fibrosis as well as the alterations in tissue structure of affected organ or body cavity. The release of a number of inflammatory mediators as well as reactive oxygen species (ROS is an important part of inflammatory response. In dairy cows, the metabolic challenge that occurred during the transition from dry period to early lactation may additionally increase the release of ROS which may contribute to development of oxidative stress and inflammatory response. Oxidative stress is defined as a shift in the balance from cellular oxidation-reduction reactions towards oxidation, i.e. to the state of excessive release of oxidants when their removal by antioxidants is impaired and even insufficient. During peripartum period antioxidantive status of dairy cows is seriously impaired and consequently both the oxidative stress and inflammatory response may present the predisposing factors to their higher susceptibility to intramammary infections (IMI and mastitis. This association between oxidative stress

  1. Peroxisome Proliferator-Activated Receptors in the Modulation of the Immune/Inflammatory Response in Atherosclerosis

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    Ana Z. Fernandez

    2008-01-01

    Full Text Available Inflammation has been recognized as an important hallmark of atherosclerosis. The pharmacological activation of PPAR- by the thiazolidinediones in diabetes, and of PPAR- by the fibrates in hyperlipidemia has been shown to help to reduce inflammatory markers in preclinical and clinical studies. PPARs are known to modulate immune pathways through at least three different mechanisms: by direct binding to PPRE of anti-inflammatory cytokines genes; by transrepression of transcription factors like NF-B and AP-1; or by corepression. The regulation of the inflammatory pathways by PPARs can be achieved on each one of the cells involved in the atherosclerotic process, that is, monocytes, macrophages, T cells, endothelial cells, and smooth muscle cells. Moreover, as each of these cellular components is interconnected with each other, PPAR activation in one cell type could affect the other ones. As activation of PPARs has clear ant-inflammatory benefits, PPARs ligands should be considered as a new therapeutical approach to ameliorate the exacerbated immune response in atherosclerotic diseases.

  2. Caffeine prevents LPS-induced inflammatory responses in RAW264.7 cells and zebrafish.

    Science.gov (United States)

    Hwang, Ji-Hyun; Kim, Kui-Jin; Ryu, Su-Jung; Lee, Boo-Yong

    2016-03-25

    Caffeine is a white crystalline xanthine alkaloid found in the seeds of coffee plants and leaves of the tea bush. In this study, we evaluated whether caffeine exerts anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation both in vitro and in vivo. RAW264.7 cells were treated with various concentrations of caffeine in the presence or absence of LPS. Caffeine decreased the LPS-induced inflammatory mediator, nitric oxide (NO). Caffeine treatment also reduced the expression of pro-inflammatory genes, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-3, IL-6 and IL-12, and decreased both IL-6 secretion and phosphorylated p38MAPK expression in LPS-treated RAW264.7 cells. Caffeine inhibited nuclear translocation of nuclear factor κB (NF-κB) via IκBα phosphorylation. In addition, caffeine inhibited LPS-induced NO production in zebrafish. These results suggest that caffeine may suppress LPS-induced inflammatory responses in RAW264.7 cells by regulating NF-κB activation and MAPK phosphorylation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. The protective effects of extra virgin olive oil on immune-mediated inflammatory responses.

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    Casas, Rosa; Estruch, Ramon; Sacanella, Emilio

    2017-11-13

    The increasing interest in the Mediterranean diet (MeDiet) hinges on the relevant role it plays in inflammatory diseases. Several clinical, epidemiological and experimental evidences suggest that consumption of the MeDiet reduces the incidence of certain pathologies related to oxidative stress, chronic inflammation and immune system diseases such as cancer, atherosclerosis and cardiovascular disease (CVD). These reductions can be partially attributed to extra virgin olive oil (EVOO) consumption which has been described as a key bioactive food because of its high nutritional quality and its particular composition of fatty acids, vitamins and polyphenols. Indeed, the beneficial effects of EVOO have been linked to its fatty acid composition, which is very rich in monounsaturated fatty acids (MUFA), and has moderate saturated and polyunsaturated fatty acids (PUFA). The current knowledge available on the beneficial effects of EVOO and its phenolic compounds, specifically its biological properties and antioxidant capacity against immune-mediated inflammatory responses (atherosclerosis, rheumatoid arthritis, diabetes, obesity, cancer, inflammatory bowel disease or neurodegenerative disease, among others) in addition to its potential clinical applications. The increasing body of studies carried out provides compelling evidence that olive polyphenols are potential candidates to combat chronic inflammatory states. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Fibrinogen modulates leukocyte recruitment in vivo during the acute inflammatory response.

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    Vitorino de Almeida, V; Silva-Herdade, A; Calado, A; Rosário, H S; Saldanha, C

    2015-01-01

    Besides playing an important role in blood hemostases, fibrinogen also regulates leukocyte function in inflammation. Our previous in vitro studies showed that the adhesive behaviour of the neutrophil is modulated by soluble fibrinogen when present at a physiological concentration. This led us to propose that this plasma glycoprotein might further influence leukocyte recruitment in vivo and thus contribute to the inflammatory response. To address this in vivo, leukocyte recruitment was here investigated under acute inflammatory conditions in the absence of soluble fibrinogen in the blood circulation. For such, intravital microscopy on mesentery post-capillary venules was performed on homozygous fibrinogen α chain-deficient mice ((α-/-) mice). Acute inflammatory states were induced by perfusing platelet activating factor (PAF) over the exposed tissue. As control animals, two groups of mice expressing soluble fibrinogen in circulation were used, namely, C57BL/6 wild type animals and heterozygous fibrinogen α chain-deficient mice ((α+/-) mice). Under acute inflammatory conditions, an abnormal pattern of recruitment was observed for leukocytes in homozygous (α-/-) mice in comparison to both control groups. In fact, the former exhibited a significantly decreased number of rolling leukocytes that nevertheless, migrated with increased rolling velocities when compared to leukocytes from control animals. Consistently, homozygous mice further displayed a diminished number of adherent leukocytes than the other groups. Altogether our observations led us to conclude that leukocyte recruitment in homozygous (α-/-) mice is compromised what strongly suggests a role for soluble fibrinogen in leukocyte recruitment in inflammation.

  5. Royal Jelly Inhibits Pseudomonas aeruginosa Adherence and Reduces Excessive Inflammatory Responses in Human Epithelial Cells

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    Heni Susilowati

    2017-01-01

    Full Text Available Pseudomonas aeruginosa is a Gram-negative bacterium and causes respiratory infection especially in elderly patients. Royal jelly has been used worldwide as a traditional remedy and as a nutrient; however, the effect against P. aeruginosa is unclear. The aim of this study was to analyze antibacterial, antiadherent, and anti-inflammatory effects of royal jelly against P. aeruginosa. Wild-type strain PAO1 and clinical isolates of P. aeruginosa were used for antibacterial assay and antiadherent assay to abiotic surface and epithelial cells, which are pharynx (Detroit 562 and lung (NCI-H292 epithelial cells. In anti-inflammatory assay, epithelial cells were pretreated with royal jelly before bacterial exposure to investigate its inhibitory effect on interleukin (IL-8 and macrophage inflammatory protein-3α/CCL20 overproduction. Although royal jelly did not have antibacterial activity at concentration of 50% w/v, antiadherent activity was confirmed on the abiotic surface and epithelial cells under concentration of 25%. Pretreatment with royal jelly significantly inhibited overproduction of IL-8 and CCL20 from both cells. These results demonstrated that royal jelly inhibits P. aeruginosa adherence and protects epithelial cells from excessive inflammatory responses against P. aeruginosa infection. Our findings suggested that royal jelly may be a useful supplement as complementary and alternative medicine for preventing respiratory infection caused by P. aeruginosa.

  6. Non-canonical Glucocorticoid Receptor Transactivation of gilz by Alcohol Suppresses Cell Inflammatory Response

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    Hang Pong Ng

    2017-06-01

    Full Text Available Acute alcohol exposure suppresses cell inflammatory response. The underlying mechanism has not been fully defined. Here we report that alcohol was able to activate glucocorticoid receptor (GR signaling in the absence of glucocorticoids (GCs and upregulated glucocorticoid-induced leucine zipper (gilz, a prominent GC-responsive gene. Such a non-canonical activation of GR was not blocked by mifepristone, a potent GC competitor. The proximal promoter of gilz, encompassing five GC-responsive elements (GREs, was incorporated and tested in a luciferase reporter system. Deletion and/or mutation of the GREs abrogated the promoter responsiveness to alcohol. Thus, the GR–GRE interaction transduced the alcohol action on gilz. Alcohol induced GR nuclear translocation, which was enhanced by the alcohol dehydrogenase inhibitor fomepizole, suggesting that it was alcohol, not its metabolites, that engendered the effect. Gel mobility shift assay showed that unliganded GR was able to bind GREs and such interaction withstood clinically relevant levels of alcohol. GR knockout via CRISPR/Cas9 gene targeting or GILZ depletion via small RNA interference diminished alcohol suppression of cell inflammatory response to LPS. Thus, a previously unrecognized, non-canonical GR activation of gilz is involved in alcohol modulation of cell immune response.

  7. Cytokine balance in human malaria: does Plasmodium vivax elicit more inflammatory responses than Plasmodium falciparum?

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    Raquel M Gonçalves

    Full Text Available BACKGROUND: The mechanisms by which humans regulate pro- and anti-inflammatory responses on exposure to different malaria parasites remains unclear. Although Plasmodium vivax usually causes a relatively benign disease, this parasite has been suggested to elicit more host inflammation per parasitized red blood cell than P. falciparum. METHODOLOGY/PRINCIPAL FINDINGS: We measured plasma concentrations of seven cytokines and two soluble tumor necrosis factor (TNF-α receptors, and evaluated clinical and laboratory outcomes, in Brazilians with acute uncomplicated infections with P. vivax (n = 85, P. falciparum (n = 30, or both species (n = 12, and in 45 asymptomatic carriers of low-density P. vivax infection. Symptomatic vivax malaria patients, compared to those infected with P. falciparum or both species, had more intense paroxysms, but they had no clear association with a pro-inflammatory imbalance. To the contrary, these patients had higher levels of the regulatory cytokine interleukin (IL-10, which correlated positively with parasite density, and elevated IL-10/TNF-α, IL-10/interferon (IFN-γ, IL-10/IL-6 and sTNFRII/TNF-α ratios, compared to falciparum or mixed-species malaria patient groups. Vivax malaria patients had the highest levels of circulating soluble TNF-α receptor sTNFRII. Levels of regulatory cytokines returned to normal values 28 days after P. vivax clearance following chemotherapy. Finally, asymptomatic carriers of low P. vivax parasitemias had substantially lower levels of both inflammatory and regulatory cytokines than did patients with clinical malaria due to either species. CONCLUSIONS: Controlling fast-multiplying P. falciparum blood stages requires a strong inflammatory response to prevent fulminant infections, while reducing inflammation-related tissue damage with early regulatory cytokine responses may be a more cost-effective strategy in infections with the less virulent P. vivax parasite. The early induction

  8. Histamine release and fibrinogen adsorption mediate acute inflammatory responses to biomaterial implants in humans

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    Eaton John W

    2007-07-01

    Full Text Available Abstract Background Medical implants often fail as a result of so-called foreign body reactions during which inflammatory cells are recruited to implant surfaces. Despite the clinical importance of this phenomenon, the mechanisms involved in these reactions to biomedical implants in humans are not well understood. The results from animal studies suggest that both fibrinogen adsorption to the implant surface and histamine release by local mast cells are involved in biomaterial-mediated acute inflammatory responses. The purpose of this study was to test this hypothesis in humans. Methods Thirteen male medical student volunteers (Caucasian, 21–30 years of age were employed for this study. To assess the importance of fibrinogen adsorption, six volunteers were implanted with polyethylene teraphthalate disks pre-coated with their own (fibrinogen-containing plasma or (fibrinogen-free serum. To evaluate the importance of histamine, seven volunteers were implanted with uncoated disks with or without prior oral administration of histamine receptor antagonists. The acute inflammatory response was estimated 24 hours later by measuring the activities of implant-associated phagocyte-specific enzymes. Results Plasma coated implants accumulated significantly more phagocytes than did serum coated implants and the recruited cells were predominantly macrophage/monocytes. Administration of both H1 and H2 histamine receptor antagonists greatly reduced the recruitment of macrophages/monocytes and neutrophils on implant surfaces. Conclusion In humans – as in rodents – biomaterial-mediated inflammatory responses involve at least two crucial events: histamine-mediated phagocyte recruitment and phagocyte accumulation on implant surfaces engendered by spontaneously adsorbed host fibrinogen. Based on these results, we conclude that reducing fibrinogen:surface interactions should enhance biocompatibility and that administration of histamine receptor antagonists prior

  9. Allicin enhances host pro-inflammatory immune responses and protects against acute murine malaria infection.

    Science.gov (United States)

    Feng, Yonghui; Zhu, Xiaotong; Wang, Qinghui; Jiang, Yongjun; Shang, Hong; Cui, Liwang; Cao, Yaming

    2012-08-08

    During malaria infection, multiple pro-inflammatory mediators including IFN-γ, TNF and nitric oxide (NO) play a crucial role in the protection against the parasites. Modulation of host immunity is an important strategy to improve the outcome of malaria infection. Allicin is the major biologically active component of garlic and shows anti-microbial activity. Allicin is also active against protozoan parasites including Plasmodium, which is thought to be mediated by inhibiting cysteine proteases. In this study, the immunomodulatory activities of allicin were assessed during acute malaria infection using a rodent malaria model Plasmodium yoelii 17XL. To determine whether allicin modulates host immune responses against malaria infection, mice were treated with allicin after infection with P. yoelii 17XL. Mortality was checked daily and parasitaemia was determined every other day. Pro-inflammatory mediators and IL-4 were quantified by ELISA, while NO level was determined by the Griess method. The populations of dendritic cells (DCs), macrophages, CD4+ T and regulatory T cells (Treg) were assessed by FACS. Allicin reduced parasitaemia and prolonged survival of the host in a dose-dependent manner. This effect is at least partially due to improved host immune responses. Results showed that allicin treatment enhanced the production of pro-inflammatory mediators such as IFN-γ, TNF, IL-12p70 and NO. The absolute numbers of CD4+ T cells, DCs and macrophages were significantly higher in allicin-treated mice. In addition, allicin promoted the maturation of CD11c+ DCs, whereas it did not cause major changes in IL-4 and the level of anti-inflammatory cytokine IL-10. Allicin could partially protect host against P. yoelii 17XL through enhancement of the host innate and adaptive immune responses.

  10. Allicin enhances host pro-inflammatory immune responses and protects against acute murine malaria infection

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    Feng Yonghui

    2012-08-01

    Full Text Available Abstract Background During malaria infection, multiple pro-inflammatory mediators including IFN-γ, TNF and nitric oxide (NO play a crucial role in the protection against the parasites. Modulation of host immunity is an important strategy to improve the outcome of malaria infection. Allicin is the major biologically active component of garlic and shows anti-microbial activity. Allicin is also active against protozoan parasites including Plasmodium, which is thought to be mediated by inhibiting cysteine proteases. In this study, the immunomodulatory activities of allicin were assessed during acute malaria infection using a rodent malaria model Plasmodium yoelii 17XL. Methods To determine whether allicin modulates host immune responses against malaria infection, mice were treated with allicin after infection with P. yoelii 17XL. Mortality was checked daily and parasitaemia was determined every other day. Pro-inflammatory mediators and IL-4 were quantified by ELISA, while NO level was determined by the Griess method. The populations of dendritic cells (DCs, macrophages, CD4+ T and regulatory T cells (Treg were assessed by FACS. Results Allicin reduced parasitaemia and prolonged survival of the host in a dose-dependent manner. This effect is at least partially due to improved host immune responses. Results showed that allicin treatment enhanced the production of pro-inflammatory mediators such as IFN-γ, TNF, IL-12p70 and NO. The absolute numbers of CD4+ T cells, DCs and macrophages were significantly higher in allicin-treated mice. In addition, allicin promoted the maturation of CD11c+ DCs, whereas it did not cause major changes in IL-4 and the level of anti-inflammatory cytokine IL-10. Conclusions Allicin could partially protect host against P. yoelii 17XL through enhancement of the host innate and adaptive immune responses.

  11. Histamine release and fibrinogen adsorption mediate acute inflammatory responses to biomaterial implants in humans

    Science.gov (United States)

    Zdolsek, Johann; Eaton, John W; Tang, Liping

    2007-01-01

    Background Medical implants often fail as a result of so-called foreign body reactions during which inflammatory cells are recruited to implant surfaces. Despite the clinical importance of this phenomenon, the mechanisms involved in these reactions to biomedical implants in humans are not well understood. The results from animal studies suggest that both fibrinogen adsorption to the implant surface and histamine release by local mast cells are involved in biomaterial-mediated acute inflammatory responses. The purpose of this study was to test this hypothesis in humans. Methods Thirteen male medical student volunteers (Caucasian, 21–30 years of age) were employed for this study. To assess the importance of fibrinogen adsorption, six volunteers were implanted with polyethylene teraphthalate disks pre-coated with their own (fibrinogen-containing) plasma or (fibrinogen-free) serum. To evaluate the importance of histamine, seven volunteers were implanted with uncoated disks with or without prior oral administration of histamine receptor antagonists. The acute inflammatory response was estimated 24 hours later by measuring the activities of implant-associated phagocyte-specific enzymes. Results Plasma coated implants accumulated significantly more phagocytes than did serum coated implants and the recruited cells were predominantly macrophage/monocytes. Administration of both H1 and H2 histamine receptor antagonists greatly reduced the recruitment of macrophages/monocytes and neutrophils on implant surfaces. Conclusion In humans – as in rodents – biomaterial-mediated inflammatory responses involve at least two crucial events: histamine-mediated phagocyte recruitment and phagocyte accumulation on implant surfaces engendered by spontaneously adsorbed host fibrinogen. Based on these results, we conclude that reducing fibrinogen:surface interactions should enhance biocompatibility and that administration of histamine receptor antagonists prior to, and shortly after

  12. Epidermal keratinocytes initiate wound healing and pro-inflammatory immune responses following percutaneous schistosome infection.

    Science.gov (United States)

    Bourke, Claire D; Prendergast, Catriona T; Sanin, David E; Oulton, Tate E; Hall, Rebecca J; Mountford, Adrian P

    2015-03-01

    Keratinocytes constitute the majority of cells in the skin's epidermis, the first line of defence against percutaneous pathogens. Schistosome larvae (cercariae) actively penetrate the epidermis to establish infection, however the response of keratinocytes to invading cercariae has not been investigated. Here we address the hypothesis that cercariae activate epidermal keratinocytes to promote the development of a pro-inflammatory immune response in the skin. C57BL/6 mice were exposed to Schistosoma mansoni cercariae via each pinna and non-haematopoietic cells isolated from epidermal tissue were characterised for the presence of different keratinocyte sub-sets at 6, 24 and 96 h p.i. We identified an expansion of epidermal keratinocyte precursors (CD45(-), CD326(-), CD34(+)) within 24 h of infection relative to naïve animals. Following infection, cells within the precursor population displayed a more differentiated phenotype (α6integrin(-)) than in uninfected skin. Parallel immunohistochemical analysis of pinnae cryosections showed that this expansion corresponded to an increase in the intensity of CD34 staining, specifically in the basal bulge region of hair follicles of infected mice, and a higher frequency of keratinocyte Ki67(+) nuclei in both the hair follicle and interfollicular epidermis. Expression of pro-inflammatory cytokine and stress-associated keratin 6b genes was also transiently upregulated in the epidermal tissue of infected mice. In vitro exposure of keratinocyte precursors isolated from neonatal mouse skin to excretory/secretory antigens released by penetrating cercariae elicited IL-1α and IL-1β production, supporting a role for keratinocyte precursors in initiating cutaneous inflammatory immune responses. Together, these observations indicate that S.mansoni cercariae and their excretory/secretory products act directly upon epidermal keratinocytes, which respond by initiating barrier repair and pro-inflammatory mechanisms similar to those

  13. Biaryl amide compounds reduce the inflammatory response in macrophages by regulating Dectin-1.

    Science.gov (United States)

    Hyung, Kyeong Eun; Lee, Mi Ji; Lee, Yun-Jung; Lee, Do Ik; Min, Hye Young; Park, So-Young; Min, Kyung Hoon; Hwang, Kwang Woo

    2016-03-01

    Macrophages are archetypal innate immune cells that play crucial roles in the recognition and phagocytosis of invading pathogens, which they identify using pattern recognition receptors (PRRs). Dectin-1 is essential for antifungal immune responses, recognizing the fungal cellular component β-glucan, and its role as a PRR has been of increasing interest. Previously, we discovered and characterized a novel biaryl amide compound, MPS 03, capable of inhibiting macrophage phagocytosis of zymosan. Therefore, in this study we aimed to identify other biaryl amide compounds with greater effectiveness than MPS 03, and elucidate their cellular mechanisms. Several MPS 03 derivatives were screened, four of which reduced zymosan phagocytosis in a similar manner to MPS 03. To establish whether such phagocytosis inhibition influenced the production of inflammatory mediators, pro-inflammatory cytokine and nitric oxide (NO) levels were measured. The production of TNF-α, IL-6, IL-12, and NO was significantly reduced in a dose-dependent manner. Moreover, the inflammation-associated MAPK signaling pathway was also affected by biaryl amide compounds. To investigate the underlying cellular mechanism, PRR expression was measured. MPS 03 and its derivatives were found to inhibit zymosan phagocytosis by decreasing Dectin-1 expression. Furthermore, when macrophages were stimulated by zymosan after pretreatment with biaryl amide compounds, downstream transcription factors such as NFAT, AP-1, and NF-κB were downregulated. In conclusion, biaryl amide compounds reduce zymosan-induced inflammatory responses by downregulating Dectin-1 expression. Therefore, such compounds could be used to inhibit Dectin-1 in immunological experiments and possibly regulate excessive inflammatory responses. Copyright © 2016. Published by Elsevier B.V.

  14. The hemic response of white-spotted bamboo sharks (Chiloscyllium plagiosum) with inflammatory disease.

    Science.gov (United States)

    Alexander, Amy B; Parkinson, Lily A; Grant, Krystan R; Carlson, Eric; Campbell, Terry W

    2016-05-01

    As elasmobranch medicine becomes more commonplace, there continues to be confusion with techniques and evaluation of the shark hemogram and it remains unknown if they are able to mount an inflammatory hemic response. The aims of this study were to compare two total white blood cell (WBC) count techniques, establish a reference interval for captive white-spotted bamboo sharks (Chiloscyllium plagiosum), and determine if elasmobranchs are capable of mounting an inflammatory hemic response. Correlation statistics were performed on hematologic results for healthy female bamboo sharks to assess the use of Natt-Herrick's and phloxine methods. Total WBC counts and differentials were obtained from males with severe traumatic clasper wounds and compared to the healthy females. We elected clasper amputation as the preferred treatment intervention and post-operative hematology was performed one month later. There was poor correlation of leukocyte counts between the two WBC count methods. Hematologic values were established for the females and males pre- and post-operatively. Males with wounds had a marked leukocytosis and heterophilia. Post-operative blood work showed a resolution of total WBC count and a trend toward resolution of the heterophilia. This study provides hematologic values for white-spotted bamboo sharks and confirms that the Natt-Herrick's method is preferred for lymphocytic species. Hematologic differences present in males with clasper wounds suggests that elasmobranchs do mount an inflammatory hemic response. Treatment via clasper amputation proved to be a safe and efficient means for clinical treatment that led to a trend toward resolution of the inflammatory leukogram. Zoo Biol. 35:251-259, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. The effects of age on inflammatory and coagulation-fibrinolysis response in patients hospitalized for pneumonia.

    Directory of Open Access Journals (Sweden)

    Sachin Kale

    2010-11-01

    Full Text Available To determine whether inflammatory and hemostasis response in patients hospitalized for pneumonia varies by age and whether these differences explain higher mortality in the elderly.In an observational cohort of subjects with community-acquired pneumonia (CAP recruited from emergency departments (ED in 28 hospitals, we divided subjects into 5 age groups (85% subjects, older subjects had modestly increased hemostasis markers and IL-6 levels (p<0.01.Modest age-related increases in coagulation response occur during hospitalization for CAP; however these differences do not explain the large differences in mortality. Despite clinical recovery, immune resolution may be delayed in older adults at discharge.

  16. Injury-Induced Type I IFN Signaling Regulates Inflammatory Responses in the Central Nervous System

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Owens, Trevor

    2010-01-01

    Innate glial response is critical for the induction of inflammatory mediators and recruitment of leukocytes to sites of the injury in the CNS. We have examined the involvement of type I IFN signaling in the mouse hippocampus following sterile injury (transection of entorhinal afferents). Type I...... in increased leukocyte infiltration into the lesion-reactive hippocampus. Axonal lesion-induced CXCL10 gene expression was abrogated, whereas matrix metalloproteinase 9 mRNA was elevated in IFNAR-deficient mice. Our findings point to a role for type I IFN signaling in regulation of CNS response to sterile...

  17. Sustainability as the basic principle of responsible budgetary policy

    Directory of Open Access Journals (Sweden)

    Anton Viktorovich Galukhin

    2014-05-01

    Full Text Available The author touches upon rather critical issues of management of the regional budget system sustainability. The prospect to studying this issue is confirmed at the highest level – by the RF President. The article indicates that the main components of the budgets financial sustainability concept are the following: the territory’s self-sufficiency (independence, its solvency, income and expenditure balance. The swot analysis of the public finances state in the Northwestern Federal District regions has revealed lowering independence of the territories, debt burden deterioration in the post-crisis period and the unsolved problem of income and expenses imbalance. The study shows the territories’ capacity constraints to find additional financial resources, although the anti-crisis instruments of the budget process (regional reserve funds are not used in full measure. The analysis has resulted in the development of directions to stimulate the regional budget system sustainability, such as the modernization model of fiscal federalism, strengthening and development of tax potential, improving the budget expenditures efficiency and encouraging the use of regional reserve funds potential. According to the author, the timeliness of these measures is to be achieved through continuous financial situation monitoring in the RF subjects

  18. The local inflammatory responses to infection of the peritoneal cavity in humans: Their regulation by cytokines, macrophages, and other leukocytes

    NARCIS (Netherlands)

    M.W.J.A. Fieren (Marien)

    2012-01-01

    textabstractStudies on infection-induced inflammatory reactions in humans rely largely on findings in the blood compartment. Peritoneal leukocytes from patients treated with peritoneal dialysis offer a unique opportunity to study in humans the inflammatory responses taking place at the site of

  19. SOCS2 and SOCS3 expression in ulcerative colitis and their correlation with inflammatory response and immune response

    Directory of Open Access Journals (Sweden)

    Le Huang1

    2017-05-01

    Full Text Available Objective: To study the correlation of SOCS2 and SOCS3 expression in ulcerative colitis tissue with inflammatory response and immune response. Methods: Ulcerative colitis lesions and normal mucosa from colonoscopic biopsy in Central Hospital of Zibo Mining Refco Group Ltd between May 2014 and July 2016 were selected and enrolled in UC group and control group respectively. RNA was extracted to determine mRNA expression of SOCS2 and SOCS3 as well as inflammatory response JAKs/STATs pathway molecules; protein was extracted to determine the contents of immune response cytokines. Results: SOCS2 mRNA expression in intestinal mucosa of UC group was not significantly different from that of control group, and SOCS3 mRNA expression was significantly lower than that of control group; JAK1, JAK2, JAK3, STAT1, STAT3 and STAT5 mRNA expression as well as IFN-γ and IL-17 protein contents in intestinal mucosa of UC group were significantly higher than those of control group while IL-4 and IL-10 protein contents were significantly lower than those of control group; JAK1, JAK2, JAK3, STAT1, STAT3 and STAT5 mRNA expression as well as IFN-γ and IL-17 protein contents in UC group of intestinal mucosa with low SOCS3 expression were significantly higher than those of intestinal mucosa with high SOCS3 expression while IL-4 and IL-10 protein contents were significantly lower than those of intestinal mucosa with high SOCS3 expression. Conclusion: Low expression of SOCS3 in ulcerative colitis can aggravate the inflammatory reaction and cause the imbalance of Th1/Th2 and Th17/Treg immune response.

  20. Inflammatory cytokines and plasma redox status responses in hypertensive subjects after heat exposure

    Directory of Open Access Journals (Sweden)

    S.F. Fonseca

    2016-03-01

    Full Text Available Hypertension is characterized by a pro-inflammatory status, including redox imbalance and increased levels of pro-inflammatory cytokines, which may be exacerbated after heat exposure. However, the effects of heat exposure, specifically in individuals with inflammatory chronic diseases such as hypertension, are complex and not well understood. This study compared the effects of heat exposure on plasma cytokine levels and redox status parameters in 8 hypertensive (H and 8 normotensive (N subjects (age: 46.5±1.3 and 45.6±1.4 years old, body mass index: 25.8±0.8 and 25.6±0.6 kg/m2, mean arterial pressure: 98.0±2.8 and 86.0±2.3 mmHg, respectively. They remained at rest in a sitting position for 10 min in a thermoneutral environment (22°C followed by 30 min in a heated environmental chamber (38°C and 60% relative humidity. Blood samples were collected before and after heat exposure. Plasma cytokine levels were measured using sandwich ELISA kits. Plasma redox status was determined by thiobarbituric acid reactive substances (TBARS levels and ferric reducing ability of plasma (FRAP. Hypertensive subjects showed higher plasma levels of IL-10 at baseline (P<0.05, although levels of this cytokine were similar between groups after heat exposure. Moreover, after heat exposure, hypertensive individuals showed higher plasma levels of soluble TNF receptor (sTNFR1 and lower TBARS (P<0.01 and FRAP (P<0.05 levels. Controlled hypertensive subjects, who use angiotensin-converting-enzyme inhibitor (ACE inhibitors, present an anti-inflammatory status and balanced redox status. Nevertheless, exposure to a heat stress condition seems to cause an imbalance in the redox status and an unregulated inflammatory response.

  1. Muscle cells challenged with saturated fatty acids mount an autonomous inflammatory response that activates macrophages

    Directory of Open Access Journals (Sweden)

    Pillon Nicolas J

    2012-10-01

    Full Text Available Abstract Obesity is associated with chronic low-grade inflammation. Within adipose tissue of mice fed a high fat diet, resident and infiltrating macrophages assume a pro-inflammatory phenotype characterized by the production of cytokines which in turn impact on the surrounding tissue. However, inflammation is not restricted to adipose tissue and high fat-feeding is responsible for a significant increase in pro-inflammatory cytokine expression in muscle. Although skeletal muscle is the major disposer of dietary glucose and a major determinant of glycemia, the origin and consequence of muscle inflammation in the development of insulin resistance are poorly understood. We used a cell culture approach to investigate the vectorial crosstalk between muscle cells and macrophages upon exposure to physiological, low levels of saturated and unsaturated fatty acids. Inflammatory pathway activation and cytokine expression were analyzed in L6 muscle cells expressing myc-tagged GLUT4 (L6GLUT4myc exposed to 0.2 mM palmitate or palmitoleate. Conditioned media thereof, free of fatty acids, were then tested for their ability to activate RAW264.7 macrophages. Palmitate -but not palmitoleate- induced IL-6, TNFα and CCL2 expression in muscle cells, through activation of the NF-κB pathway. Palmitate (0.2 mM alone did not induce insulin resistance in muscle cells, yet conditioned media from palmitate-challenged muscle cells selectively activated macrophages towards a pro-inflammatory phenotype. These results demonstrate that low concentrations of palmitate activate autonomous inflammation in muscle cells to release factors that turn macrophages pro-inflammatory. We hypothesize that saturated fat-induced, low-grade muscle cell inflammation may trigger resident skeletal muscle macrophage polarization, possibly contributing to insulin resistance in vivo.

  2. CORPORATE GOVERNANCE, SOCIAL RESPONSIBILITY AND SUSTAINABILITY A SURVEY OF WATER USE IN INDUSTRY

    National Research Council Canada - National Science Library

    DOINA PRODAN PALADE; LEON DUMITRU DANIEL

    2015-01-01

    ...’ corporate governance and social responsibility. The work aims to highlight some of the main issues regarding the sustainable use of water, as a finite and vulnerable resource, essential element for life and environment...

  3. When not every response to climate change is a good one: identifying principles for sustainable adaptation

    CSIR Research Space (South Africa)

    Eriksen, S

    2011-01-01

    Full Text Available ; third, integrate local knowledge into adaptation responses; and fourth, consider potential feedbacks between local and global processes. We argue that fundamental societal transformations are required in order to achieve sustainable development pathways...

  4. Extracellular Adenosine Generation in the Regulation of Pro-Inflammatory Responses and Pathogen Colonization

    Directory of Open Access Journals (Sweden)

    M. Samiul Alam

    2015-05-01

    Full Text Available Adenosine, an immunomodulatory biomolecule, is produced by the ecto-enzymes CD39 (nucleoside triphosphate dephosphorylase and CD73 (ecto-5'-nucleotidase by dephosphorylation of extracellular ATP. CD73 is expressed by many cell types during injury, infection and during steady-state conditions. Besides host cells, many bacteria also have CD39-CD73-like machinery, which helps the pathogen subvert the host inflammatory response. The major function for adenosine is anti-inflammatory, and most recent research has focused on adenosine’s control of inflammatory mechanisms underlying various autoimmune diseases (e.g., colitis, arthritis. Although adenosine generated through CD73 provides a feedback to control tissue damage mediated by a host immune response, it can also contribute to immunosuppression. Thus, inflammation can be a double-edged sword: it may harm the host but eventually helps by killing the invading pathogen. The role of adenosine in dampening inflammation has been an area of active research, but the relevance of the CD39/CD73-axis and adenosine receptor signaling in host defense against infection has received less attention. Here, we review our recent knowledge regarding CD73 expression during murine Salmonellosis and Helicobacter-induced gastric infection and its role in disease pathogenesis and bacterial persistence. We also explored a possible role for the CD73/adenosine pathway in regulating innate host defense function during infection.

  5. Different inflammatory responses induced by three LDL-lowering apheresis columns.

    Science.gov (United States)

    Hovland, Anders; Hardersen, Randolf; Sexton, Joe; Mollnes, Tom Eirik; Lappegård, Knut Tore

    2009-01-01

    Low-density lipoprotein (LDL) apheresis is well-established in selected patients with uncontrolled LDL levels. As such treatment affects biomarkers important in atherosclerosis and acute coronary syndromes, we systematically compared the inflammatory response induced by three LDL apheresis columns. Three patients with heterozygous familial hypercholesterolemia participated in a cross-over study with six consecutive treatments with three different LDL apheresis columns: DL-75 (whole blood adsorption), LA-15 (plasma adsorption), and EC-50W (plasma filtration). Biochemical parameters and inflammatory biomarkers, including complement activation products and 27 cytokines, chemokines, and growth factors were measured before and after treatment. Complement was activated through the alternative pathway. The final end product sC5b-9 increased significantly (P < 0.01) and equally with all devices, whereas the anaphylatoxins C3a and C5a were lower by use of the adsorption columns. Hs-CRP was reduced by 77% (DL-75), 72% (LA-15), and 43% (EC-50W). The cytokines were consistently either increased (IL-1ra, IP-10, MCP-1), decreased (IFN-gamma, TNF-alpha, RANTES, PDGF, VEGF), or hardly changed (including IL-6, IL8, MIP-1alphabeta) during treatment. The changes were in general less pronounced with the adsorption columns. All columns reduced LDL significantly and to the same extent. In conclusion, three LDL-apheresis devices with equal cholesterol-lowering effect differed significantly with respect to the inflammatory response.

  6. Integrin-substrate interactions underlying shear-induced inhibition of the inflammatory response of endothelial cells.

    Science.gov (United States)

    Luu, N Thin; Glen, Katie E; Egginton, Stuart; Rainger, G Ed; Nash, Gerard B

    2013-02-01

    Conditioning of endothelial cells by shear stress suppresses their response to inflammatory cytokines. We questioned whether signalling through different integrin-matrix interactions, previously associated with the pathogenic effects of disturbed flow, supported the anti-inflammatory action of steady shear. Primary human endothelial cells were cultured on different substrates and exposed to shear stress (2.0Pa) for varying periods before stimulation with tumour necrosis factor-α (TNF). Shear-conditioning inhibited cytokine-induced recruitment of flowing neutrophils. However, the effect was similar for culture on collagen, laminin or fibronectin, even when seeding was reduced to 2 hours, and shear to 3 hours before TNF treatment (to minimise deposition of endothelial matrix). Nevertheless, in short- or longer-term cultures, reduction in expression of β(1)-integrin (but not β(3)-integrin) using siRNA essentially ablated the effect of shear-conditioning on neutrophil recruitment. Studies of focal adhesion kinase (FAK) phosphorylation, siRNA against FAK and a FAK-inhibitor (PF573228) indicated that FAK activity was an essential component downstream of β(1)-integrin. In addition, MAP-kinase p38 was phosphorylated downstream of FAK and also required for functional modification. Mechanotransduction through β(1)-integrins, FAK and p38 is required for anti-inflammatory effects of steady shear stress. Separation of the pathways which underlie pathological versus protective responses of different patterns of flow is required to enable therapeutic modification or mimicry, respectively.

  7. Protective effect of taraxasterol against rheumatoid arthritis by the modulation of inflammatory responses in mice

    Science.gov (United States)

    Jiang, Shu-Hua; Ping, Li-Feng; Sun, Feng-Yan; Wang, Xiao-Lei; Sun, Zhi-Juan

    2016-01-01

    Taraxasterol is an effective component of dandelion that has anti-inflammatory effects in vivo and in vitro. The present study was performed to explore whether taraxasterol exhibits a protective effect against rheumatoid arthritis through the modulation of inflammatory responses in mice. Eight-week-old CCR9-deficient mice were injected with a collagen II monoclonal antibody cocktail to create a rheumatoid arthritis model. In the experimental group, arthritic model mice were treated with 10 mg/kg taraxasterol once per day for 5 days. Treatment with taraxasterol significantly increased the pain thresholds and reduced the clinical arthritic scores of the mice in the experimental group compared with those of the model group. Furthermore, treatment with taraxasterol significantly suppressed tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and nuclear factor-κB protein expression levels compared with those in the rheumatoid arthritis model mice. Taraxasterol treatment also significantly reduced nitric oxide, prostaglandin E2 and cyclooxygenase-2 levels compared with those in the rheumatoid arthritis model group. These observations indicate that the protective effect of taraxasterol against rheumatoid arthritis is mediated via the modulation of inflammatory responses in mice. PMID:28101182

  8. Lipid Bodies: Inflammatory Organelles Implicated in Host-Trypanosoma cruzi Interplay during Innate Immune Responses

    Directory of Open Access Journals (Sweden)

    Heloisa D'Avila

    2012-01-01

    Full Text Available The flagellated protozoa Trypanosoma cruzi is the causal agent of Chagas' disease, a significant public health issue and still a major cause of morbidity and mortality in Latin America. Acute Chagas' disease elicits a strong inflammatory response. In order to control the parasite multiplication, cells of the monocytic lineage are highly mobilized. Monocyte differentiation leads to the formation of phagocytosing macrophages, which are strongly activated and direct host defense. A distinguishing feature of Chagas' disease-triggered macrophages is the presence of increased numbers of distinct cytoplasmic organelles termed lipid bodies or lipid droplets. These organelles are actively formed in response to the parasite and are sites for synthesis and storage of inflammatory mediators. This review covers current knowledge on lipid bodies elicited by the acute Chagas' disease within inflammatory macrophages and discusses the role of these organelles in inflammation. The increased knowledge of lipid bodies in pathogenic mechanisms of infections may not only contribute to the understanding of pathogen-host interactions but may also identify new targets for intervention.

  9. Acute-Phase Inflammatory Response to Single-Bout HIIT and Endurance Training: A Comparative Study.

    Science.gov (United States)

    Kaspar, Felix; Jelinek, Herbert F; Perkins, Steven; Al-Aubaidy, Hayder A; deJong, Bev; Butkowski, Eugene

    2016-01-01

    This study compared acute and late effect of single-bout endurance training (ET) and high-intensity interval training (HIIT) on the plasma levels of four inflammatory cytokines and C-reactive protein and insulin-like growth factor 1. Cohort study with repeated-measures design. Seven healthy untrained volunteers completed a single bout of ET and HIIT on a cycle ergometer. ET and HIIT sessions were held in random order and at least 7 days apart. Blood was drawn before the interventions and 30 min and 2 days after the training sessions. Plasma samples were analyzed with ELISA for the interleukins (IL), IL-1β, IL-6, and IL-10, monocyte chemoattractant protein-1 (MCP-1), insulin growth factor 1 (IGF-1), and C-reactive protein (CRP). Statistical analysis was with Wilcoxon signed-rank tests. ET led to both a significant acute and long-term inflammatory response with a significant decrease at 30 minutes after exercise in the IL-6/IL-10 ratio (-20%; p = 0.047) and a decrease of MCP-1 (-17.9%; p = 0.03). This study demonstrates that ET affects the inflammatory response more adversely at 30 minutes after exercise compared to HIIT. However, this is compensated by a significant decrease in MCP-1 at two days associated with a reduced risk of atherosclerosis.

  10. Hypoxia modulates phenotype, inflammatory response, and leishmanial infection of human dendritic cells.

    Science.gov (United States)

    Bosseto, Maira Cegatti; Palma, Patricia Vianna Bonini; Covas, Dimas Tadeu; Giorgio, Selma

    2010-02-01

    Development of hypoxic areas occurs during infectious and inflammatory processes and dendritic cells (DCs) are involved in both innate and adaptive immunity in diseased tissues. Our group previously reported that macrophages exposed to hypoxia were infected with the intracellular parasite Leishmania amazonensis, but showed reduced susceptibility to the parasite. This study shows that although hypoxia did not alter human DC viability, it significantly altered phenotypic and functional characteristics. The expression of CD1a, CD80, and CD86 was significantly reduced in DCs exposed to hypoxia, whereas CD11c, CD14, CD123, CD49 and HLA-DR expression remained unaltered in DCs cultured in hypoxia or normoxia. DC secretion of IL-12p70, the bioactive interleukin-12 (IL-12), a cytokine produced in response to inflammatory mediators, was enhanced under hypoxia. In addition, phagocytic activity (Leishmania uptake) was not impaired under hypoxia, although this microenviroment induced infected DCs to reduce parasite survival, consequently controlling the infection rate. All these data support the notion that a hypoxic microenvironment promotes selective pressure on DCs to assume a phenotype characterized by pro-inflammatory and microbial activities in injured or inflamed tissues and contribute to the innate immune response.

  11. The Inhibitory Effect of Tartary Buckwheat Extracts on Adipogenesis and Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Mak-Soon Lee

    2017-07-01

    Full Text Available Tartary buckwheat (Fagopyrum tataricum has been established globally as a nutritionally important food item, particularly owing to high levels of bioactive compounds such as rutin. This study investigated the effect of tartary buckwheat extracts (TBEs on adipogenesis and inflammatory response in 3T3-L1 cells. TBEs inhibited lipid accumulation, triglyceride content, and glycerol-3-phosphate dehydrogenase (GPDH activity during adipocyte differentiation of 3T3 L1 cells. The mRNA levels of genes involved in fatty acid synthesis, such as peroxisome proliferator-activated receptor-γ (PPAR-γ, CCAAT/enhancer binding protein-α (CEBP-α, adipocyte protein 2 (aP2, acetyl-CoA carboxylase (ACC, fatty acid synthase (FAS, and stearoylcoenzyme A desaturase-1 (SCD-1, were suppressed by TBEs. They also reduced the mRNA levels of inflammatory mediators such as tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, monocyte chemoattractant protein 1 (MCP-1, and inducible nitric oxide synthase (iNOS. In addition, TBEs were decreased nitric oxide (NO production. These results suggest that TBEs may inhibit adipogenesis and inflammatory response; therefore, they seem to be beneficial as a food ingredient to prevent obesity-associated inflammation.

  12. Gastrodin relieved complete Freund's adjuvant-induced spontaneous pain by inhibiting inflammatory response.

    Science.gov (United States)

    Sun, Ting; Wang, Jian; Li, Xiang; Li, Yu-Jiao; Feng, Dan; Shi, Wen-Long; Zhao, Ming-Gao; Wang, Jian-Bo; Wu, Yu-Mei

    2016-12-01

    The analgesic effects of gastrodin (GAS), an active component derived from the Chinese herb Tian ma (Gastrodia elata Blume), on chronic inflammatory pain of mice and the involved molecular mechanisms were investigated. GAS significantly attenuated mice chronic inflammatory pain induced by hindpaw injection of complete Freund's adjuvant (CFA) and the accompanying anxiety-like behaviors. GAS administration reduced CFA-induced up-regulation of GluR1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, GluN2A- and GluN2B-containing N-methyl-d-aspartate (NMDA) receptors, and Ca(2+)/calmodulin-dependent protein kinase II-alpha (CaMKII-α) in the anterior cingulate cortex (ACC). The GluN2A and GluN2B subunits of NMDA receptors, the GluR1 type of AMPA receptor, and CaMKII-α are key molecules responsible for neuroplasticity involved in chronic pain and the accompanying anxiety. Moreover, GAS administration reduced the activation of astrocyte and microglia and the induction of TNF-α and IL-6 in the ACC of the CFA-injected mice. Therefore, GAS administration relieved chronic pain, exerted anxiolytic effects by regulating neuroplasticity molecules, and attenuated the inflammatory response by reducing the induction of TNF-α and IL-6 in the ACC of the CFA-injected mice. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Role of histamine in the inhibitory effects of phycocyanin in experimental models of allergic inflammatory response.

    Science.gov (United States)

    Remirez, D; Ledón, N; González, R

    2002-01-01

    It has recently been reported that phycocyanin, a biliprotein found in the blue-green microalgae Spirulina, exerts anti-inflammatory effects in some animal models of inflammation. Taking into account these findings, we decided to elucidate whether phycocyanin might exert also inhibitory effects in the induced allergic inflammatory response and on histamine release from isolated rat mast cells. In in vivo experiments, phycocyanin (100, 200 and 300mg/kg post-orally (p.o.)) was administered 1 h before the challenge with 1 microg of ovalbumin (OA) in the ear of mice previously sensitized with OA. One hour later, myeloperoxidase activity and ear edema were assessed. Phycocyanin significantly reduced both parameters. In separate experiments, phycocyanin (100 and 200 mg/kg p.o.) also reduced the blue spot area induced by intradermal injections of histamine, and the histamine releaser compound 48/80 in rat skin. In concordance with the former results, phycocyanin also significantly reduced histamine release induced by compound 48/80 from isolated peritoneal rat mast cells. The inhibitory effects of phycocyanin were dose dependent. Taken together, our results suggest that inhibition of allergic inflammatory response by phycocyanin is mediated, at least in part, by inhibition of histamine release from mast cells. PMID:12061428

  14. Nuclear Control of the Inflammatory Response in Mammals by Peroxisome Proliferator-Activated Receptors

    Directory of Open Access Journals (Sweden)

    Stéphane Mandard

    2013-01-01

    Full Text Available Peroxisome proliferator-activated receptors (PPARs are ligand-activated transcription factors that play pivotal roles in the regulation of a very large number of biological processes including inflammation. Using specific examples, this paper focuses on the interplay between PPARs and innate immunity/inflammation and, when possible, compares it among species. We focus on recent discoveries establishing how inflammation and PPARs interact in the context of obesity-induced inflammation and type 2 diabetes, mostly in mouse and humans. We illustrate that PPARγ ability to alleviate obesity-associated inflammation raises an interesting pharmacologic potential. In the light of recent findings, the protective role of PPARα and PPARβ/δ against the hepatic inflammatory response is also addressed. While PPARs agonists are well-established agents that can treat numerous inflammatory issues in rodents and humans, surprisingly very little has been described in other species. We therefore also review the implication of PPARs in inflammatory bowel disease; acute-phase response; and central, cardiac, and endothelial inflammation and compare it along different species (mainly mouse, rat, human, and pig. In the light of the data available in the literature, there is no doubt that more studies concerning the impact of PPAR ligands in livestock should be undertaken because it may finally raise unconsidered health and sanitary benefits.

  15. HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Mudan Lu

    2015-01-01

    Full Text Available Background/Purpose. HMGB1, which may act as a proinflammatory mediator, has been proposed to contribute to the pathogenesis of multiple chronic inflammatory and autoimmune diseases including systemic lupus erythematosus (SLE; however, the precise mechanism of HMGB1 in the pathogenic process of SLE remains obscure. Method. The expression of HMGB1 was measured by ELISA and western blot. The ELISA was also applied to detect proinflammatory cytokines levels. Furthermore, nephritic pathology was evaluated by H&E staining of renal tissues. Results. In this study, we found that HMGB1 levels were significantly increased and correlated with SLE disease activity in both clinical patients and murine model. Furthermore, gain- and loss-of-function analysis showed that HMGB1 exacerbated the severity of SLE. Of note, the HMGB1 levels were found to be associated with the levels of proinflammatory cytokines such as TNF-α and IL-6 in SLE patients. Further study demonstrated that increased HMGB1 expression deteriorated the severity of SLE via enhancing macrophage inflammatory response. Moreover, we found that receptor of advanced glycation end products played a critical role in HMGB1-mediated macrophage inflammatory response. Conclusion. These findings suggested that HMGB1 might be a risk factor for SLE, and manipulation of HMGB1 signaling might provide a therapeutic strategy for SLE.

  16. Suppressive effects of lysozyme on polyphosphate-mediated vascular inflammatory responses.

    Science.gov (United States)

    Chung, Jiwoo; Ku, Sae-Kwang; Lee, Suyeon; Bae, Jong-Sup

    2016-06-10

    Lysozyme, found in relatively high concentration in blood, saliva, tears, and milk, protects us from the ever-present danger of bacterial infection. Previous studies have reported proinflammatory responses of endothelial cells to the release of polyphosphate(PolyP). In this study, we examined the anti-inflammatory responses and mechanisms of lysozyme and its effects on PolyP-induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behavior of human neutrophils, and vascular permeability were determined in PolyP-activated HUVECs and mice. Lysozyme suppressed the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/or production of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6. Furthermore, lysozyme demonstrated protective effects on PolyP-mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of lysozyme on various systemic inflammatory diseases, such as sepsis or septic shock. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication

    Directory of Open Access Journals (Sweden)

    Gefei Wang

    2016-01-01

    Full Text Available Unlike stereotypical neurotropic viruses, influenza A viruses have been detected in the brain tissues of human and animal models. To investigate the interaction between neurons and influenza A viruses, mouse cortical neurons were isolated, infected with human H1N1 influenza virus, and then examined for the production of various inflammatory molecules involved in immune response. We found that replication of the influenza virus in neurons was limited, although early viral transcription was not affected. Virus-induced neuron viability decreased at 6 h postinfection (p.i. but increased at 24 h p.i. depending upon the viral strain. Virus-induced apoptosis and cytopathy in primary cortical neurons were not apparent at 24 h p.i. The mRNA levels of inflammatory cytokines, chemokines, and type I interferons were upregulated at 6 h and 24 h p.i. These results indicate that the influenza virus induces inflammatory response in mouse primary cortical neurons with limited viral replication. The cytokines released in viral infection-induced neuroinflammation might play critical roles in influenza encephalopathy, rather than in viral replication-induced cytopathy.

  18. Role of histamine in the inhibitory effects of phycocyanin in experimental models of allergic inflammatory response

    Directory of Open Access Journals (Sweden)

    D. Remirez

    2002-01-01

    Full Text Available It has recently been reported that phycocyanin, a biliprotein found in the blue-green microalgae Spirulina, exerts anti-inflammatory effects in some animal models of inflammation. Taking into account these findings, we decided to elucidate whether phycocyanin might exert also inhibitory effects in the induced allergic inflammatory response and on histamine release from isolated rat mast cells. In in vivo experiments, phycocyanin (100, 200 and 300 mg/kg post-orally (p.o. was administered 1 h before the challenge with 1 μg of ovalbumin (OA in the ear of mice previously sensitized with OA. One hour later, myeloperoxidase activity and ear edema were assessed. Phycocyanin significantly reduced both parameters. In separate experiments, phycocyanin (100 and 200 mg/kg p.o. also reduced the blue spot area induced by intradermal injections of histamine, and the histamine releaser compound 48/80 in rat skin. In concordance with the former results, phyco-cyanin also significantly reduced histamine release induced by compound 48/80 from isolated peritoneal rat mast cells. The inhibitory effects of phycocyanin were dose dependent. Taken together, our results suggest that inhibition of allergic inflammatory response by phycocyanin is mediated, at least in part, by inhibition of histamine release from mast cells.

  19. Influential Factors and Strategy of Sustainable Product Development under Corporate Social Responsibility in Taiwan

    Directory of Open Access Journals (Sweden)

    Jui-Che Tu

    2013-01-01

    Full Text Available This study aimed to adopt the perspective of corporate social responsibility (CSR to explore the intention of sustainable product development in Taiwan, as well as leading to the creation of influential factors that affect corporate sustainable product development intention. In this research, the induction analysis was conducted to understand the implementation of sustainable product development, and this was supplemented with questionnaire surveys and in-depth interviews to evaluate developmental intention. In addition, principal component analysis was used for factor analysis and content analysis in the 6 W expression method, leading to the creation of the influential factors. The research results have demonstrated that the factors affecting the intention of corporate sustainable product development include having a sustainable design and a development purpose, a corporate development purpose, sustainable development concepts, a sustainable design value, a sustainability concept, and a manufacturing process quality. For sustainable product development, corporate social responsibility needs to be most concerned with the added value of products, regulation requirements, and accommodation of the industrial chain, costs, and quality.

  20. Corporate social responsibility as a factor of sustainable development

    OpenAIRE

    N. Suprun

    2009-01-01

    The author investigates the bases of corporate social responsibility as a factor of balanced socio-economic development and increase in competitiveness of the business and social sectors. The article provides analysis of the tendencies of the formation of corporate social responsibility in the world business practice and defines priorities of the development of corporate social responsibility in Ukraine.

  1. Differences in postprandial inflammatory responses to a 'modern' v. traditional meat meal: a preliminary study.

    Science.gov (United States)

    Arya, Fatemeh; Egger, Sam; Colquhoun, David; Sullivan, David; Pal, Sebely; Egger, Garry

    2010-09-01

    A low-grade inflammatory response ('metaflammation') has been found to be associated with certain chronic diseases. Proposed inducers of this have been aspects of the modern lifestyle, including newly introduced foods. Plasma TAG, and the inflammatory cytokines C-reactive protein (CRP), TNF-alpha and IL-6 were compared in a randomised, cross-over trial using ten healthy subjects before and after eating 100 g of kangaroo, or a 'new' form of hybridised beef (wagyu) separated by about 1 week. Postprandial levels for 1 and 2 h of TAG, IL-6 and TNF-alpha were significantly higher after eating wagyu compared with kangaroo (P = 0.002 for TAG at 1 h, P meat (kangaroo). Further studies using isoenergetic intake and isolating fatty acid components of meats are proposed.

  2. Equol suppresses inflammatory response and bone erosion due to rheumatoid arthritis in mice.

    Science.gov (United States)

    Lin, I-Chian; Yamashita, Shuya; Murata, Motoki; Kumazoe, Motofumi; Tachibana, Hirofumi

    2016-06-01

    Rheumatoid arthritis (RA) is a chronic and systemic autoimmune inflammatory disease. Typical pathological findings of RA include persistent synovitis and bone degradation in the peripheral joints. Equol, a metabolite of the major soybean isoflavone daidzein, shows superior bioactivity than other isoflavones. We investigated the effects of equol administration on inflammatory response and bone erosion in mice with collagen-induced arthritis (CIA). The severity of arthritis symptoms was significantly low in the equol-administered CIA mice. In addition, equol administration improved the CIA-induced bone mineral density decline. In the inflamed area of CIA mice, equol administration suppressed the expression of interleukin-6 and its receptor. Furthermore, equol reduced the expression of genes associated with bone formation inhibition, osteoclast and immature osteoblast specificity and cartilage destruction. These results suggest that equol suppresses RA development and RA-induced bone erosion by regulating inflammation and bone metabolism. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses

    Science.gov (United States)

    Aho, Vilma; Ollila, Hanna M.; Kronholm, Erkki; Bondia-Pons, Isabel; Soininen, Pasi; Kangas, Antti J.; Hilvo, Mika; Seppälä, Ilkka; Kettunen, Johannes; Oikonen, Mervi; Raitoharju, Emma; Hyötyläinen, Tuulia; Kähönen, Mika; Viikari, Jorma S.A.; Härmä, Mikko; Sallinen, Mikael; Olkkonen, Vesa M.; Alenius, Harri; Jauhiainen, Matti; Paunio, Tiina; Lehtimäki, Terho; Salomaa, Veikko; Orešič, Matej; Raitakari, Olli T.; Ala-Korpela, Mika; Porkka-Heiskanen, Tarja

    2016-01-01

    Sleep loss and insufficient sleep are risk factors for cardiometabolic diseases, but data on how insufficient sleep contributes to these diseases are scarce. These questions were addressed using two approaches: an experimental, partial sleep restriction study (14 cases and 7 control subjects) with objective verification of sleep amount, and two independent epidemiological cohorts (altogether 2739 individuals) with questions of sleep insufficiency. In both approaches, blood transcriptome and serum metabolome were analysed. Sleep loss decreased the expression of genes encoding cholesterol transporters and increased expression in pathways involved in inflammatory responses in both paradigms. Metabolomic analyses revealed lower circulating large HDL in the population cohorts among subjects reporting insufficient sleep, while circulating LDL decreased in the experimental sleep restriction study. These findings suggest that prolonged sleep deprivation modifies inflammatory and cholesterol pathways at the level of gene expression and serum lipoproteins, inducing changes toward potentially higher risk for cardiometabolic diseases. PMID:27102866

  4. Dihydro-CDDO-trifluoroethyl amide suppresses inflammatory responses in macrophages via activation of Nrf2

    Energy Technology Data Exchange (ETDEWEB)

    Li, Bin [Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012 (China); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States); Abdalrahman, Akram; Lai, Yimu; Janicki, Joseph S. [Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States); Ward, Keith W.; Meyer, Colin J. [Department of Pharmacology, Reata Pharmaceuticals, Inc., Irving, TX 75063 (United States); Wang, Xing Li [Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012 (China); Tang, Dongqi, E-mail: Dongqi.Tang@uscmed.sc.edu [Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012 (China); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States); Cui, Taixing, E-mail: taixing.cui@uscmed.sc.edu [Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012 (China); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States)

    2014-02-21

    Highlights: • Dh404 suppresses the expression of a selected set of pro-inflammatory cytokines in inflamed macrophages via activating Nrf2. • Dh404 activates Nrf2 while keeping Keap1 function intact in macrophages. • Dh404 minimally regulates NF-κB pathway in macrophages. - Abstract: Nuclear factor erythroid 2-related factor (Nrf2) is the major regulator of cellular defenses against various pathological stresses in a variety of organ systems, thus Nrf2 has evolved to be an attractive drug target for the treatment and/or prevention of human disease. Several synthetic oleanolic triterpenoids including dihydro-CDDO-trifluoroethyl amide (dh404) appear to be potent activators of Nrf2 and exhibit chemopreventive promises in multiple disease models. While the pharmacological efficacy of Nrf2 activators may be dependent on the nature of Nrf2 activation in specific cell types of target organs, the precise role of Nrf2 in mediating biological effects of Nrf2 activating compounds in various cell types remains to be further explored. Herein we report a unique and Nrf2-dependent anti-inflammatory profile of dh404 in inflamed macrophages. In lipopolysaccharide (LPS)-inflamed RAW264.7 macrophages, dh404 dramatically suppressed the expression of pro-inflammatory cytokines including inducible nitric oxide synthase (iNOS), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1 beta (MIP-1β), while minimally regulating the expression of interleulin-6 (IL-6), IL-1β, and tumor necrosis factor alpha (TNFα). Dh404 potently activated Nrf2 signaling; however, it did not affect LPS-induced NF-κB activity. Dh404 did not interrupt the interaction of Nrf2 with its endogenous inhibitor Kelch-like ECH associating protein 1 (Keap1) in macrophages. Moreover, knockout of Nrf2 blocked the dh404-induced anti-inflammatory responses in LPS-inflamed macrophages. These results demonstrated that dh404 suppresses pro-inflammatory responses in macrophages via an activation

  5. Effects of propofol and desflurane anaesthesia on the alveolar inflammatory response to one-lung ventilation.

    Science.gov (United States)

    Schilling, T; Kozian, A; Kretzschmar, M; Huth, C; Welte, T; Bühling, F; Hedenstierna, G; Hachenberg, T

    2007-09-01

    One-lung ventilation (OLV) induces a pro-inflammatory response including cytokine release and leucocyte recruitment in the ventilated lung. Whether volatile or i.v. anaesthetics differentially modulate the alveolar inflammatory response to OLV is unclear. Thirty patients, ASA II or III, undergoing open thoracic surgery were randomized to receive either propofol 4 mg kg(-1) h(-1) (n = 15) or 1 MAC desflurane in air (n = 15) during thoracic surgery. Analgesia was provided by i.v. infusion of remifentanil (0.25 microg kg(-1) min(-1)) in both groups. The patients were mechanically ventilated according to a standard protocol during two-lung ventilation and OLV. Fibre optic bronchoalveolar lavage (BAL) of the ventilated lung was performed before and after OLV and 2 h postoperatively. Alveolar cells, protein, tumour necrosis factor alpha (TNFalpha), interleukin (IL)-8, soluble intercellular adhesion molecule-1 (sICAM), IL10, and polymorphonuclear (PMN) elastase were determined in the BAL fluid. Data were analysed by parametric or non-parametric tests, as indicated. In both groups, an increase in pro-inflammatory markers was found after OLV and 2 h postoperatively; however, the fraction of alveolar granulocytes (median 63.7 vs 31.1%, P < 0.05) was significantly higher in the propofol group compared with the desflurane group. The time courses of alveolar elastase, IL-8, and IL-10 differed between groups, and alveolar TNFalpha (7.4 vs 3.1 pg ml(-1), P < 0.05) and sICAM-1 (52.3 vs 26.3 ng ml(-1), P < 0.05) were significantly higher in the propofol group. These data indicate that pro-inflammatory reactions during OLV were influenced by the type of general anaesthesia. Different patterns of alveolar cytokines may be a result of increased granulocyte recruitment during propofol anaesthesia.

  6. Absent in melanoma 2 (AIM2) in rat dental pulp mediates the inflammatory response during pulpitis.

    Science.gov (United States)

    Wang, Yafei; Zhai, Shafei; Wang, Haijing; Jia, Qian; Jiang, Wenkai; Zhang, Xiao; Zhang, Ansheng; Liu, Jun; Ni, Longxing

    2013-11-01

    In recent years, the inflammasome has been determined to play an important role in inflammatory diseases. However, the role of the inflammasome in pulpitis remains unclear. Absent in melanoma 2 (AIM2) is a type of inflammasome that recognizes cytosolic double stranded DNA and forms a caspase-1-activating inflammasome with apoptosis-associated speck-like protein containing a caspase activating recruiting domain. In this study, we determined whether AIM2 was expressed in pulp cells and defined the role of AIM2 in the initiation of inflammation within the dental pulp. In the in vivo study, the right maxillary molars from male adult Sprague-Dawley rats (250-350 g) were exposed to the pulp. In the in vitro study, the pulp cells isolated from the mandibular incisors of the Sprague-Dawley rats (2 weeks) were conventionally cultured. Immunofluorescence staining was used to determine the expression and distribution of AIM2 in the rat dental pulp tissues and cells in the presence or absence of inflammatory stimulation. Western blotting and real-time polymerase chain reaction were performed to determine whether there was a correlation between AIM2 expression levels and inflammation both in vivo and in vitro. In healthy dental pulp tissues and cells, AIM2 was only detected in the odontoblast layer. Stimulation significantly increased AIM2 expression in both the dental pulp tissues and cultured cells. The mRNA and protein levels of AIM2 were significantly up-regulated in response to inflammatory stimulation in a dose-dependent manner. Moreover, we also found that AIM2 expression correlated with interleukin-1 levels. These results reveal a direct relationship between the AIM2 inflammasome and pulpitis. Our study demonstrates that AIM2 is expressed in dental pulp tissues and mediates the inflammatory response during pulpitis. Therapeutic interventions aimed at reducing AIM2 expression may be beneficial in the treatment of pulpitis. Copyright © 2013 American Association of

  7. Sex differences in the inflammatory response of primary astrocytes to lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Santos-Galindo María

    2011-07-01

    Full Text Available Abstract Background Numerous neurological and psychiatric disorders show sex differences in incidence, age of onset, symptomatology or outcome. Astrocytes, one of the glial cell types of the brain, show sex differences in number, differentiation and function. Since astrocytes are involved in the response of neural tissue to injury and inflammation, these cells may participate in the generation of sex differences in the response of the brain to pathological insults. To explore this hypothesis, we have examined whether male and female astrocytes show a different response to an inflammatory challenge and whether perinatal testosterone influences this response. Methods Cortical astrocyte cultures were prepared from postnatal day 1 (one day after birth male or female CD1 mice pups. In addition, cortical astrocyte cultures were also prepared from female pups that were injected at birth with 100 μg of testosterone propionate or vehicle. Cultures were treated for 5 hours with medium containing lipopolysaccharide (LPS or with control medium. The mRNA levels of IL6, interferon-inducible protein 10 (IP10, TNFα, IL1β, Toll-like receptor 4 (TLR4, steroidogenic acute regulatory protein and translocator protein were assessed by quantitative real-time polymerase chain reaction. Statistical significance was assessed by unpaired t-test or by one-way analysis of variance followed by the Tukey post hoc test. Results The mRNA levels of IL6, TNFα and IL1β after LPS treatment were significantly higher in astrocytes derived from male or androgenized females compared to astrocytes derived from control or vehicle-injected females. In contrast, IP10 mRNA levels after LPS treatment were higher in astrocytes derived from control or vehicle-injected females than in those obtained from males or androgenized females. The different response of male and female astrocytes to LPS was due neither to differences in the basal expression of the inflammatory molecules nor to

  8. 11β-Hydroxysteroid dehydrogenase 1 contributes to the pro-inflammatory response of keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Itoi, Saori; Terao, Mika, E-mail: mterao@derma.med.osaka-u.ac.jp; Murota, Hiroyuki; Katayama, Ichiro

    2013-10-18

    Highlights: •We investigate the role of 11β-HSD1 in skin inflammation. •Various stimuli increase expression of 11β-HSD1 in keratinocytes. •11β-HSD1 knockdown by siRNA decreases cortisol levels in media. •11β-HSD1 knockdown abrogates the response to pro-inflammatory cytokines. •Low-dose versus high-dose cortisol has opposing effects on keratinocyte inflammation. -- Abstract: The endogenous glucocorticoid, cortisol, is released from the adrenal gland in response to various stress stimuli. Extra-adrenal cortisol production has recently been reported to occur in various tissues. Skin is known to synthesize cortisol through a de novo pathway and through an activating enzyme. The enzyme that catalyzes the intracellular conversion of hormonally-inactive cortisone into active cortisol is 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). We recently reported that 11β-HSD1 is expressed in normal human epidermal keratinocytes (NHEKs) and negatively regulates proliferation of NHEKs. In this study, we investigated the role of 11β-HSD1 in skin inflammation. Expression of 11β-HSD1 was induced by UV-B irradiation and in response to the pro-inflammatory cytokines, IL-1β and TNFα. Increased cortisol concentrations in culture media also increased in response to these stimuli. To investigate the function of increased 11β-HSD1 in response to pro-inflammatory cytokines, we knocked down 11β-HSD1 by transfecting siRNA. Production of IL-6 and IL-8 in response to IL-1β or TNFα stimulation was attenuated in NHEKs transfected with si11β-HSD1 compared with control cells. In addition, IL-1β-induced IL-6 production was enhanced in cultures containing 1 × 10{sup −13} M cortisol, whereas 1 × 10{sup −5} M cortisol attenuated production of IL-6. Thus, cortisol showed immunostimulatory and immunosuppressive activities depending on its concentration. Our results indicate that 11β-HSD1 expression is increased by various stimuli. Thus, regulation of cytosolic cortisol

  9. Addressing the Inflammatory Response to Clinically Relevant Polymers by Manipulating the Host Response Using ITIM Domain-Containing Receptors

    Directory of Open Access Journals (Sweden)

    Joshua B. Slee

    2014-09-01

    Full Text Available Tissue contacting surfaces of medical devices initiate a host inflammatory response, characterized by adsorption of blood proteins and inflammatory cells triggering the release of cytokines, reactive oxygen species (ROS and reactive nitrogen species (RNS, in an attempt to clear or isolate the foreign object from the body. This normal host response contributes to device-associated pathophysiology and addressing device biocompatibility remains an unmet need. Although widespread attempts have been made to render the device surfaces unreactive, the establishment of a completely bioinert coating has been untenable and demonstrates the need to develop strategies based upon the molecular mechanisms that define the interaction between host cells and synthetic surfaces. In this review, we discuss a family of transmembrane receptors, known as immunoreceptor tyrosine-based inhibitory motif (ITIM-containing receptors, which show promise as potential targets to address aberrant biocompatibility. These receptors repress the immune response and ensure that the intensity of an immune response is appropriate for the stimuli. Particular emphasis will be placed on the known ITIM-containing receptor, Signal Regulatory Protein Alpha (SIRPα, and its cognate ligand CD47. In addition, this review will discuss the potential of other ITIM-containing proteins as targets for addressing the aberrant biocompatibility of polymeric biomaterials.

  10. Cross-sex transplantation alters gene expression and enhances inflammatory response in the transplanted kidneys.

    Science.gov (United States)

    Wang, Lei; Song, Jiangping; Wang, Shaohui; Buggs, Jacentha; Chen, Rongjun; Zhang, Jie; Wang, Liqing; Rong, Song; Li, Wenbin; Wei, Jin; Liu, Ruisheng

    2017-08-01

    Kidney transplantation (KTX) is a life-saving procedure for patients with end-stage renal disease. Expression levels of many genes in the kidney vary between males and females, which may play an essential role in the sex differences in graft function. However, whether these differences are affected after cross-sex-KTX is unknown. In the present study, we assessed postoperative changes in genotype, function, and inflammatory responses of the grafts in same-sex- and cross-sex-KTX. Single kidney transplants were performed between same and different sex C57BL/6 mice paired into four combination groups: female donor/female recipient (F/F); male donor/male recipient (M/M); female donor/male recipient (F/M); and male donor/female recipient (M/F). The remnant native kidney was removed 4 days posttransplant. Expression levels of genes related to the contractility of the afferent arteriole and tubular sodium reabsorption were assessed. Same-sex-KTX did not significantly alter the magnitude or sex difference pattern of gene expression in male or female grafts. Cross-sex-KTX showed an attenuated sex difference in gene expressions. The measurements of endothelin 1, endothelin ETA receptor, Na+-K--2Cl cotransporter 2 (NKCC2), and epithelial Na+ channels (ENaC) subunits exhibited decreases in M/F compared with M/M and increases in F/M compared with F/F. There were no significant differences in hemodynamics or sodium excretion in response to acute volume expansion for any sex combinations. Cross-sex-KTX stimulated more robust inflammatory responses than same-sex-KTX. IL-6 and KC mRNA levels elevated 5- to 20-fold in cross-sex-KTX compared with same-sex-KTX. In conclusion, cross-sex-KTX alters gene expression levels and induces inflammatory responses, which might play an important role in long-term graft function. Copyright © 2017 the American Physiological Society.

  11. Food deprivation alters thermoregulatory responses to lipopolysaccharide by enhancing cryogenic inflammatory signaling via prostaglandin D2.

    Science.gov (United States)

    Krall, Catherine M; Yao, Xiujuan; Hass, Martha A; Feleder, Carlos; Steiner, Alexandre A

    2010-06-01

    We tested the hypothesis that food deprivation alters body temperature (T(b)) responses to bacterial LPS by enhancing inflammatory signaling that decreases T(b) (cryogenic signaling) rather than by suppressing inflammatory signaling that increases T(b) (febrigenic signaling). Free-feeding or food-deprived (24 h) rats received LPS at doses (500 and 2,500 microg/kg iv) that are high enough to activate both febrigenic and cryogenic signaling. At these doses, LPS caused fever in rats at an ambient temperature of 30 degrees C, but produced hypothermia at an ambient temperature of 22 degrees C. Whereas food deprivation had little effect on LPS fever, it enhanced LPS hypothermia, an effect that was particularly pronounced in rats injected with the higher LPS dose. Enhancement of hypothermia was not due to thermogenic incapacity, since food-deprived rats were fully capable of raising T(b) in response to the thermogenic drug CL316,243 (1 mg/kg iv). Neither was enhancement of hypothermia associated with altered plasma levels of cytokines (TNF-alpha, IL-1beta, and IL-6) or with reduced levels of an anti-inflammatory hormone (corticosterone). The levels of PGD(2) and PGE(2) during LPS hypothermia were augmented by food deprivation, although the ratio between them remained unchanged. Food deprivation, however, selectively enhanced the responsiveness of rats to the cryogenic action of PGD(2) (100 ng icv) without altering the responsiveness to febrigenic PGE(2) (100 ng icv). These findings support our hypothesis and indicate that cryogenic signaling via PGD(2) underlies enhancement of LPS hypothermia by food deprivation.

  12. Training reduces catabolic and inflammatory response to a single practice in female volleyball players.

    Science.gov (United States)

    Eliakim, Alon; Portal, Shawn; Zadik, Zvi; Meckel, Yoav; Nemet, Dan

    2013-11-01

    We examined the effect of training on hormonal and inflammatory response to a single volleyball practice in elite adolescent players. Thirteen female, national team level, Israeli volleyball players (age 16.0 ± 1.4 years, Tanner stage 4-5) participated in the study. Blood samples were collected before and immediately after a typical 60 minutes of volleyball practice, before and after 7 weeks of training during the initial phase of the season. Training involved tactic and technical drills (20% of time), power and speed drills (25% of time), interval sessions (25% of time), endurance-type training (15% of time), and resistance training (15% of time). To achieve greater training responses, the study was performed during the early phase (first 7 weeks) of the volleyball season. Hormonal measurements included the anabolic hormones growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein-3, the catabolic hormone cortisol, the proinflammatory marker interleukin-6 (IL-6), and the anti-inflammatory marker IL-1 receptor antagonist. Training led to a significant improvement of vertical jump, anaerobic properties (peak and mean power by the Wingate Anaerobic Test), and predicted VO2max (by the 20-m shuttle run). Volleyball practice, both before and after the training intervention, was associated with a significant increase of serum lactate, GH, and IL-6. Training resulted in a significantly reduced cortisol response ([INCREMENT]cortisol: 4.2 ± 13.7 vs. -4.4 ± 12.3 ng · ml, before and after training, respectively; p volleyball practice. The results suggest that along with the improvement of power and anaerobic and aerobic characteristics, training reduces the catabolic and inflammatory response to exercise.

  13. AMP-activated protein kinase reduces inflammatory responses and cellular senescence in pulmonary emphysema.

    Science.gov (United States)

    Cheng, Xiao-Yu; Li, Yang-Yang; Huang, Cheng; Li, Jun; Yao, Hong-Wei

    2017-04-04

    Current drug therapy fails to reduce lung destruction of chronic obstructive pulmonary disease (COPD). AMP-activated protein kinase (AMPK) has emerged as an important integrator of signals that control energy balance and lipid metabolism. However, there are no studies regarding the role of AMPK in reducing inflammatory responses and cellular senescence during the development of emphysema. Therefore, we hypothesize that AMPK reduces inflammatroy responses, senescence, and lung injury. To test this hypothesis, human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (SAECs) were treated with cigarette smoke extract (CSE) in the presence of a specific AMPK activator (AICAR, 1 mM) and inhibitor (Compound C, 5 μM). Elastase injection was performed to induce mouse emphysema, and these mice were treated with a specific AMPK activator metformin as well as Compound C. AICAR reduced, whereas Compound C increased CSE-induced increase in IL-8 and IL-6 release and expression of genes involved in cellular senescence. Knockdown of AMPKα1/α2 increased expression of pro-senescent genes (e.g., p16, p21, and p66shc) in BEAS-2B cells. Prophylactic administration of an AMPK activator metformin (50 and 250 mg/kg) reduced while Compound C (4 and 20 mg/kg) aggravated elastase-induced airspace enlargement, inflammatory responses and cellular senescence in mice. This is in agreement with therapeutic effect of metformin (50 mg/kg) on airspace enlargement. Furthermore, metformin prophylactically protected against but Compound C further reduced mitochondrial proteins SOD2 and SIRT3 in emphysematous lungs. In conclusion, AMPK reduces abnormal inflammatory responses and cellular senescence, which implicates as a potential therapeutic target for COPD/emphysema.

  14. Neural mechanisms linking social status and inflammatory responses to social stress

    Science.gov (United States)

    Dedovic, Katarina; Slavich, George M.; Jarcho, Michael R.; Breen, Elizabeth C.; Bower, Julienne E.; Irwin, Michael R.; Eisenberger, Naomi I.

    2016-01-01

    Social stratification has important implications for health and well-being, with individuals lower in standing in a hierarchy experiencing worse outcomes than those higher up the social ladder. Separate lines of past research suggest that alterations in inflammatory processes and neural responses to threat may link lower social status with poorer outcomes. This study was designed to bridge these literatures to investigate the neurocognitive mechanisms linking subjective social status and inflammation. Thirty-one participants reported their subjective social status, and underwent a functional magnetic resonance imaging scan while they were socially evaluated. Participants also provided blood samples before and after the stressor, which were analysed for changes in inflammation. Results showed that lower subjective social status was associated with greater increases in inflammation. Neuroimaging data revealed lower subjective social status was associated with greater neural activity in the dorsomedial prefrontal cortex (DMPFC) in response to negative feedback. Finally, results indicated that activation in the DMPFC in response to negative feedback mediated the relation between social status and increases in inflammatory activity. This study provides the first evidence of a neurocognitive pathway linking subjective social status and inflammation, thus furthering our understanding of how social hierarchies shape neural and physiological responses to social interactions. PMID:26979965

  15. Neural mechanisms linking social status and inflammatory responses to social stress.

    Science.gov (United States)

    Muscatell, Keely A; Dedovic, Katarina; Slavich, George M; Jarcho, Michael R; Breen, Elizabeth C; Bower, Julienne E; Irwin, Michael R; Eisenberger, Naomi I

    2016-06-01

    Social stratification has important implications for health and well-being, with individuals lower in standing in a hierarchy experiencing worse outcomes than those higher up the social ladder. Separate lines of past research suggest that alterations in inflammatory processes and neural responses to threat may link lower social status with poorer outcomes. This study was designed to bridge these literatures to investigate the neurocognitive mechanisms linking subjective social status and inflammation. Thirty-one participants reported their subjective social status, and underwent a functional magnetic resonance imaging scan while they were socially evaluated. Participants also provided blood samples before and after the stressor, which were analysed for changes in inflammation. Results showed that lower subjective social status was associated with greater increases in inflammation. Neuroimaging data revealed lower subjective social status was associated with greater neural activity in the dorsomedial prefrontal cortex (DMPFC) in response to negative feedback. Finally, results indicated that activation in the DMPFC in response to negative feedback mediated the relation between social status and increases in inflammatory activity. This study provides the first evidence of a neurocognitive pathway linking subjective social status and inflammation, thus furthering our understanding of how social hierarchies shape neural and physiological responses to social interactions. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  16. Characterisation of the cytokine inflammatory response in LPS stimulated full-term cord blood.

    Science.gov (United States)

    Powell, Corrina; Orsi, Nicolas; Simpson, Nigel; Levene, Malcolm

    2004-01-01

    Abnormal inflammatory responses are implicated in the pathogenesis of neonatal disease. This study aimed to describe the neonatal cytokine response using an in vitro model of stimulated cord blood. Cord blood samples (n = 12) were incubated in RPMI 1640 medium with and without lipopolysaccharide. Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, interferon (IFN)-gamma and IL-10 were determined by multiplex immunoassay at 0, 1, 3, 6 and 24 hours of incubation. The difference between stimulated and control response was defined as the potential secretory capacity (mean +/- S.E.M.; pg/million white cells). Analysis included a Kruskal-Wallis test and post-hoc Mann-Whitney U test. All cytokine capacities increased rapidly by 1 hour (p<0.001), except IL-10 (p=0.04). TNF-alpha peaked between 3-6 hours (1581 +/- 377 pg/million WC), declining by 24 hours. Similarly, IFN-gamma peaked at 3 hours. Capacity ascended throughout the incubation period for IL-6, IL-8 (631 +/- 75 pg/million WC) and IL-10 (311 +/- 37 pg/million WC). Overall, IFN-gamma capacity was lowest (72 +/- 10 pg/million WC) and IL-6 capacity was greatest (61489 +/- 7059 pg/million WC). The neonatal inflammatory response is chronologically similar to that determined in adults. Immature neonatal T-cell function may account for the lower IFN-gamma production. These results may expand our knowledge of neonatal disease, etiology and management.

  17. Correlation of neonatal pulmonary surfactant protein A gene polymorphism with pneumonia susceptibility and inflammatory response

    Directory of Open Access Journals (Sweden)

    Yi He

    2017-06-01

    Full Text Available Objective: To study the correlation of neonatal pulmonary surfactant protein A gene polymorphism with pneumonia susceptibility and inflammatory response. Methods: Neonates who were born and diagnosed with pneumonia in Zigong Maternity and Child Healthcare Hospital between September 2015 and February 2017 were selected as pneumonia group, and neonates without infection were selected as control group. SP-A gene rs1059054 and rs1136454 loci polymorphism, the contents of inflammatory cytokines in serum as well as the expression of inflammatory transcription factors in peripheral blood were determined. Results: The constituent ratio of rs1059054 loci CC genotype of pneumonia group was significantly higher than that of control group while the constituent ratio of CT and TT genotypes were significantly lower than those of control group; the constituent ratio of rs1136454 loci AA genotype was significantly lower than that of control group while the constituent ratio of AG and GG genotypes were significantly higher than those of control group. PCT, sTREM1, TNF-α and IL-6 levels in serum as well as RORγt mRNA expression in peripheral blood of pneumonia children with SP-A gene rs1059054 loci CC genotype were significantly higher than those of pneumonia children with CT genotype and TT genotype while SOCS1 and Foxp3 mRNA expression in peripheral blood were significantly lower than those of pneumonia children with CT genotype and TT genotype; PCT, sTREM1, TNF-α and IL-6 levels in serum as well as RORγt mRNA expression in peripheral blood of pneumonia children with SP-A gene rs1136454 loci AA genotype were significantly lower than those of pneumonia children with AG genotype and GG genotype while SOCS1 and Foxp3 mRNA expression in peripheral blood were significantly higher than those of pneumonia children with AG genotype and GG genotype. Conclusion: Neonatal SP-A gene rs1059054 loci CC genotype can increase the pneumonia susceptibility and aggravate

  18. Shift Work in Rats Results in Increased Inflammatory Response after Lipopolysaccharide Administration: A Role for Food Consumption.

    Science.gov (United States)

    Guerrero-Vargas, Natalí N; Guzmán-Ruiz, Mara; Fuentes, Rebeca; García, Joselyn; Salgado-Delgado, Roberto; Basualdo, María del Carmen; Escobar, Carolina; Markus, Regina P; Buijs, Ruud M

    2015-08-01

    The suprachiasmatic nucleus (SCN) drives circadian rhythms in behavioral and physiological variables, including the inflammatory response. Shift work is known to disturb circadian rhythms and is associated with increased susceptibility to develop disease. In rodents, circadian disruption due to shifted light schedules (jet lag) induced increased innate immune responses. To gain more insight into the influence of circadian disruption on the immune response, we characterized the inflammatory response in a model of rodent shift work and demonstrated that circadian disruption affected the inflammatory response to lipopolysaccharide (LPS) both in vivo and in vitro. Since food consumption is a main disturbing element in the shift work schedule, we also evaluated the inflammatory response to LPS in a group of rats that had no access to food during their working hours. Our results demonstrated that the shift work schedule decreased basal TNF-α levels in the liver but not in the circulation. Despite this, we observed that shift work induced increased cytokine response after LPS stimulation in comparison to control rats. Also, Kupffer cells (liver macrophages) isolated from shift work rats produced more TNF-α in response to in vitro LPS stimulation, suggesting important effects of circadian desynchronization on the functionality of this cell type. Importantly, the effects of shift work on the inflammatory response to LPS were prevented when food was not available during the working schedule. Together, these results show that dissociating behavior and food intake from the synchronizing drive of the SCN severely disturbs the immune response. © 2015 The Author(s).

  19. Sustainable Marketing - a new Era in the Responsible Marketing Development

    National Research Council Canada - National Science Library

    Marek Seretny; Aleksandra Seretny

    2012-01-01

    ... processes - the responsibility which rests upon them in the face of rapid social change worldwide through increasing global economic turbulence, a continuously widening gap between rich and poor...

  20. Apelin protect against multiple organ injury following hemorrhagic shock and decrease the inflammatory response

    National Research Council Canada - National Science Library

    Soliman, Mona; Arafah, Maha

    2015-01-01

    .... Apelin has anti-inflammatory effects on the release of inflammatory mediators. To examine the protective effects of apelin against multiple organ injury and the possible involvement of inflammatory pathways...

  1. Sustainable Development and Corporate Social Responsibility in Sub-Saharan Africa: Evidence from Industries in Cameroon

    Directory of Open Access Journals (Sweden)

    Oyewole Simon Oginni

    2016-05-01

    Full Text Available Present technological innovations and social organizations continue to impose risks and limitations on the efficient performance of the biosphere. Human activities have increasingly short-lived sustainable natural endowments, to the extent that, the multiplier effects have ripples beyond the traditional benefits of economic production and consumption. Therefore, this study addressed practical concerns on how industries in Sub-Saharan Africa promote sustainable development in their corporate social responsibility models, using industries in Cameroon as a case study; it examined economic, social, and environmental components of sustainable development and corporate social responsibility (CSR. Our sample consists of 335 business enterprises from the last Censure Survey of Enterprises in Cameroon. The study adopted a systematic analysis through the Adjusted Residual Test, and the Phi and Cramer’s V tests. Findings revealed that industries in Cameroon prioritize environmental and social dimensions over economic dimensions. However, a few large enterprises implement a broad CSR that promotes sustainable business practices, whereas smaller ones do not; industries in Cameroon implement environmental dimensions of CSR as a safe buffer and a social dimension as philanthropy. Hence, there is no concrete evidence that industries promote sustainable development via CSR in Cameroon. The implementation of a sustainable business model is a precondition for promoting sustainable development via CSR. Industries should realize the concrete value in implementing a sustainable business model that helps to adjust to the complex and increasingly changing business environment.

  2. ALCOHOL ABUSE ENHANCES SYSTEMIC INFLAMMATORY RESPONSE IN PATIENTS AFTER SPONTANEOUS INTRACEREBRAL HAEMORRHAGE

    Directory of Open Access Journals (Sweden)

    Maya Danovska

    2010-11-01

    Full Text Available OBJECTIVE: The role of inflammation in the complex pathophysiology of spontaneous intracerebral hemorrhage (sICH was studied by assessing the relationship between serum C-reactive protein (CRP levels and some clinical and neuroradiological parameters. We also aimed to identify the effects of modifiable vascular risk factors on serum CRP levels.PATIENTS: Forty six patients with sICH admitted to the Department of Neurology and Neurosurgery of the Pleven University Hospital, Bulgaria were examined. Serum CRP levels were measured within the first 48 hours of disease onset and analyzed in relation to neurological deficit severity and clinical outcome after sICH. The impact of some vascular risk factors on the inflammatory marker levels was also studied.RESULTS: We found enhanced CRP levels in patients with severe neurological deficit as assessed by the National Institutes of Health Stroke Scale (NIHSS score. Significantly higher CRP levels were measured in patients with progressive clinical deterioration and worse outcome. Serum CRP levels were also higher in patients with a history of alcohol abuse.CONCLUSIONS: Our results suggest that inflammation plays a crucial role in the development of brain injury after sICH. They show that CRP, a nonspecific inflammatory marker, can serve as an additional diagnostic and prognostic test indicator in the acute stage of sICH thus providing an excellent opportunity for therapeutic interventions while the patient is still in clinic. Patients with a history of systemic alcohol abuse demonstrate stronger inflammatory response indicative for worse prognosis.

  3. Dietary supplementation with fish oil modifies the ability of human monocytes to induce an inflammatory response.

    Science.gov (United States)

    Luu, Nguyet-Thin; Madden, Jackie; Calder, Philip C; Grimble, Robert F; Shearman, Cliff P; Chan, Tim; Dastur, Neville; Howell, William M; Rainger, G Ed; Nash, Gerard B

    2007-12-01

    Monocytes/macrophages are key orchestrators of inflammation and are involved in the pathogenesis of chronic inflammatory disorders, including atherosclerosis. (n-3) Fatty acids, found in fish oil, have been shown to have protective effects in such disorders. To investigate possible modes of action, we used a monocyte:endothelial cell (EC) coculture model to investigate the pro-inflammatory potential of monocytes. Monocytes were isolated from the blood of donors with peripheral arterial disease (PAD) or control donors, before and after a 12-wk supplementation of their diet with fish oil. The monocytes were cultured with human umbilical vein EC (HUVEC) for 24 h, after which the ability of the HUVEC to recruit flowing neutrophils was tested. Monocytes from either group of donors stimulated the EC to support the adhesion and migration of neutrophils. Fish oil supplementation reduced the potency of monocytes from normal subjects, but not those from patients with PAD, to induce recruitment. Concurrent medication may have acted as a complicating factor. On subgroup analysis, only those free of medication showed a significant effect of fish oil. Responses before or after supplementation were not closely linked to patterns of secretion of cytokines by cultured monocytes, tested in parallel monocultures. These results suggest that fish oil can modulate the ability of monocytes to stimulate EC and that this might contribute to their protective effects against chronic inflammatory disorders. Benefits, however, may depend on existing medical status and on other treatments being received.

  4. Effects of Thymol and Carvacrol, Constituents of Thymus vulgaris L. Essential Oil, on the Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Fernanda Carolina Fachini-Queiroz

    2012-01-01

    Full Text Available Thyme (Thymus vulgaris L., Lamiaceae is an aromatic and medicinal plant that has been used in folk medicine, phytopharmaceutical preparations, food preservatives, and as an aromatic ingredient. The effect of Thymus vulgaris essential oil (TEO and its isolated constituents thymol and cavacrol (CVL were studied in the following experimental models: ear edema, carrageenan-induced pleurisy, and chemotaxis in vitro. In the pleurisy model, TEO, CVL, and thymol significantly inhibited inflammatory edema. However, only TEO and CVL inhibited leukocyte migration. In the in vitro chemotaxis experiment, CVL inhibited leukocyte migration, whereas thymol exerted a potent chemoattractant effect. In the ear edema model, CVL (10 mg/ear, applied topically, reduced edema formation, exerting a topical anti-inflammatory effect. Thymol did not reduce edema formation but rather presented an irritative response, probably dependent on histamine and prostanoid release. Our data suggest that the antiinflammatory effects of TEO and CVL are attributable to the inhibition of inflammatory edema and leukocyte migration.

  5. Cytokine Reduction in the Setting of an ARDS-Associated Inflammatory Response with Multiple Organ Failure

    Directory of Open Access Journals (Sweden)

    Karl Träger

    2016-01-01

    Full Text Available A 45-year-old male was admitted to our hospital with a small bowel obstruction due to torsion and was immediately scheduled for surgical intervention. At anesthesia induction, the patient aspirated and subsequently developed a severe SIRS with ARDS and multiple organ failure requiring the use of ECMO, CRRT, antibiotics, and low dose steroids. Due to a rapid deterioration in clinical status and a concurrent surge in inflammatory biomarkers, an extracorporeal cytokine adsorber (CytoSorb was added to the CRRT blood circuit. The combined treatment resulted in a rapid and significant reduction in the levels of circulating inflammatory mediators. This decrease was paralleled by marked clinical stabilization of the patient including a significant improvement in hemodynamic stability and a reduced need for norepinephrine and improved respiratory function as measured by PaO2/FIO2, ventilator parameters, lung mechanics, and indirect measures of capillary leak syndrome. The patient could be discharged to a respiratory weaning unit where successful respiratory weaning could be achieved later on. We attribute the clinical improvement to the rapid control of the hyperinflammatory response and the reduction of inflammatory mediators using a combination of CytoSorb and these other therapies. CytoSorb treatment was safe and well tolerated, with no device-related adverse effects observed.

  6. Obesity and coronary microvascular disease - implications for adipose tissue-mediated remote inflammatory response.

    Science.gov (United States)

    Bagi, Zsolt; Broskova, Zuzana; Feher, Attila

    2014-05-01

    It is believed that obesity has detrimental effects on the coronary circulation. These include immediate changes in coronary arterial vasomotor responsiveness and the development of occlusive large coronary artery disease. Despite its critical role in regulating myocardial perfusion, the altered behavior of coronary resistance arteries, which gives rise to coronary microvascular disease (CMD) is poorly understood in obesity. A chronic, low-grade vascular inflammation has been long considered as one of the main underlying pathology behind CMD. The expanded adipose tissue and the infiltrating macrophages are the major sources of pro-inflammatory mediators that have been implicated in causing inadequate myocardial perfusion and, in a long term, development of heart failure in obese patients. Much less is known the mechanisms regulating the release of these cytokines into the circulation that enable them to exert their remote effects in the coronary microcirculation. This mini review aims to examine recent studies describing alterations in the vasomotor function of coronary resistance arteries and the role of adipose tissue-derived pro-inflammatory cytokines and adipokines in contributing to CMD in obesity. We provide examples of regulatory mechanisms by which adipokines are released from adipose tissue to exert their remote inflammatory effects on coronary microvessels. We identify some of the important challenges and opportunities going forward.

  7. Annatto carotenoids attenuate oxidative stress and inflammatory response after high-calorie meal in healthy subjects.

    Science.gov (United States)

    Roehrs, Miguel; Conte, Lisiane; da Silva, Dariane Trivisiol; Duarte, Thiago; Maurer, Luana Haselein; de Carvalho, José Antonio Mainardi; Moresco, Rafael Noal; Somacal, Sabrina; Emanuelli, Tatiana

    2017-10-01

    The aim of this study was to evaluate the effect of annatto carotenoids intake associated to a single high-calorie meal (high fat and high carbohydrate) in postprandial biochemical, inflammatory and oxidative stress markers. Twelve healthy subjects (6 men, 6 women) were included in this randomised, controlled crossover study. Baseline blood samples were collected from fasting subjects that immediately received high-calorie meal without carotenoid (placebo) or containing 1.2mg/kg bixin (BIX) or 0.06mg/kg norbixin (NBIX). Blood samples were taken 60, 120 and 240min after meal intake. NBIX intake did not affect biochemical blood markers but reduced the postprandial levels of inflammatory cytokines (IL-1, IL-6 and TNF-α) and lipid oxidation 60-120min after meal. BIX only partially prevented postprandial-induced lipid oxidation. Results indicate that the intake of NBIX may be an alternative to reduce the postprandial inflammatory and oxidative stress responses to high-calorie meals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Effects Of Different PUFA Supplementation On Inflammatory Response Markers In Young Soccer Players

    Directory of Open Access Journals (Sweden)

    Radoman Kristina

    2015-12-01

    Full Text Available Considering the limited knowledge regarding the effects of n-3 and n-6 PUFAs on the inflammatory response during physical activity, we aimed to evaluate the level of pro- and anti-inflammatory cytokines in young soccer players before and after a maximal physical load test at the beginning and end of a two-month training process. The study included 75 young footballers from Football School “Kragujevac,” who were followed during the two-month training programme. The subjects were divided into the following groups: 1 control group (consumed a standard diet; 2 group that consumed fish oil (2500 mg of n-3 PUFAs per day; 3 group that consumed nutritional sunflower oil (2500 mg of n-6 PUFAs daily. The maximal progressive exercise test was performed using a treadmill belt. Venous blood samples were drawn 4 times for the determination of cytokine levels (IL-6 and TNF-α: before and after the exercise load test before the two-month training programme (initial measurement and immediately before and after the exercise load test after the two-month training programme (control measurement. Supplementation with fish oil (n-3 has been associated with reduced levels of IL-6 compared with the initial values. After an acute bout of exercise, n-3 PUFAs did not show a significant effect on inflammatory marker dynamics, whereas n-6 PUFAs slightly stimulated the production of TNF-α.

  9. Mycobacterial PIMs inhibit host inflammatory responses through CD14-dependent and CD14-independent mechanisms.

    Directory of Open Access Journals (Sweden)

    Nathalie Court

    Full Text Available Mycobacteria develop strategies to evade the host immune system. Among them, mycobacterial LAM or PIMs inhibit the expression of pro-inflammatory cytokines by activated macrophages. Here, using synthetic PIM analogues, we analyzed the mode of action of PIM anti-inflammatory effects. Synthetic PIM(1 isomer and PIM(2 mimetic potently inhibit TNF and IL-12 p40 expression induced by TLR2 or TLR4 pathways, but not by TLR9, in murine macrophages. We show inhibition of LPS binding to TLR4/MD2/CD14 expressing HEK cells by PIM(1 and PIM(2 analogues. More specifically, the binding of LPS to CD14 was inhibited by PIM(1 and PIM(2 analogues. CD14 was dispensable for PIM(1 and PIM(2 analogues functional inhibition of TLR2 agonists induced TNF, as shown in CD14-deficient macrophages. The use of rough-LPS, that stimulates TLR4 pathway independently of CD14, allowed to discriminate between CD14-dependent and CD14-independent anti-inflammatory effects of PIMs on LPS-induced macrophage responses. PIM(1 and PIM(2 analogues inhibited LPS-induced TNF release by a CD14-dependent pathway, while IL-12 p40 inhibition was CD14-independent, suggesting that PIMs have multifold inhibitory effects on the TLR4 signalling pathway.

  10. Mycobacterial PIMs inhibit host inflammatory responses through CD14-dependent and CD14-independent mechanisms.

    Science.gov (United States)

    Court, Nathalie; Rose, Stéphanie; Bourigault, Marie-Laure; Front, Sophie; Martin, Olivier R; Dowling, Jennifer K; Kenny, Elaine F; O'Neill, Luke; Erard, François; Quesniaux, Valerie F J

    2011-01-01

    Mycobacteria develop strategies to evade the host immune system. Among them, mycobacterial LAM or PIMs inhibit the expression of pro-inflammatory cytokines by activated macrophages. Here, using synthetic PIM analogues, we analyzed the mode of action of PIM anti-inflammatory effects. Synthetic PIM(1) isomer and PIM(2) mimetic potently inhibit TNF and IL-12 p40 expression induced by TLR2 or TLR4 pathways, but not by TLR9, in murine macrophages. We show inhibition of LPS binding to TLR4/MD2/CD14 expressing HEK cells by PIM(1) and PIM(2) analogues. More specifically, the binding of LPS to CD14 was inhibited by PIM(1) and PIM(2) analogues. CD14 was dispensable for PIM(1) and PIM(2) analogues functional inhibition of TLR2 agonists induced TNF, as shown in CD14-deficient macrophages. The use of rough-LPS, that stimulates TLR4 pathway independently of CD14, allowed to discriminate between CD14-dependent and CD14-independent anti-inflammatory effects of PIMs on LPS-induced macrophage responses. PIM(1) and PIM(2) analogues inhibited LPS-induced TNF release by a CD14-dependent pathway, while IL-12 p40 inhibition was CD14-independent, suggesting that PIMs have multifold inhibitory effects on the TLR4 signalling pathway.

  11. Trail (TNF-related apoptosis-inducing ligand) induces an inflammatory response in human adipocytes.

    Science.gov (United States)

    Zoller, Verena; Funcke, Jan-Bernd; Roos, Julian; Dahlhaus, Meike; Abd El Hay, Muad; Holzmann, Karlheinz; Marienfeld, Ralf; Kietzmann, Thomas; Debatin, Klaus-Michael; Wabitsch, Martin; Fischer-Posovszky, Pamela

    2017-07-18

    High serum concentrations of TNF-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor protein family, are found in patients with increased BMI and serum lipid levels. In a model of murine obesity, both the expression of TRAIL and its receptor (TRAIL-R) is elevated in adipose tissue. Accordingly, TRAIL has been proposed as an important mediator of adipose tissue inflammation and obesity-associated diseases. The aim of this study was to investigate if TRAIL regulates inflammatory processes at the level of the adipocyte. Using human Simpson-Golabi-Behmel syndrome (SGBS) cells as a model system, we found that TRAIL induces an inflammatory response in both preadipocytes and adipocytes. It stimulates the expression of interleukin 6 (IL-6), interleukin 8 (IL-8) as well as the chemokines monocyte chemoattractant protein-1 (MCP-1) and chemokine C-C motif ligand 20 (CCL-20) in a time- and dose-dependent manner. By using small molecule inhibitors, we found that both the NFκB and the ERK1/2 pathway are crucial for mediating the effect of TRAIL. Taken together, we identified a novel pro-inflammatory function of TRAIL in human adipocytes. Our findings suggest that targeting the TRAIL/TRAIL-R system might be a useful strategy to tackle obesity-associated adipose tissue inflammation.

  12. Piperine attenuates lipopolysaccharide (LPS)-induced inflammatory responses in BV2 microglia.

    Science.gov (United States)

    Wang-Sheng, Chen; Jie, An; Jian-Jun, Li; Lan, Hong; Zeng-Bao, Xing; Chang-Qing, Li

    2017-01-01

    Piperine, the chief alkaloid isolated from Piper nigrum, has been known to have anti-inflammatory effect. However, the effects of piperine on neuroinflammation have not been reported. In the present study, we evaluated the effects of piperine on neuroinflammation in BV2 microglia and investigated the molecular mechanism. The results showed that piperine significantly inhibited LPS-induced TNF-α, IL-6, IL-1β, and PGE2 production in BV2 cells. Western blot analysis showed that piperine dose-dependently inhibited LPS-induced NF-κB activation. Furthermore, piperine was found to amplify the expression of Nrf2 and HO-1 up-regulated by LPS. In addition, the inhibition of inflammatory mediators by piperine can be reversed by transfection with Nrf2 siRNA. In conclusion, piperine inhibited LPS-induced inflammatory response by activating Nrf2 signaling pathway. These results indicated that piperine may be a promising agent for the treatment of neurodegenerative diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Crocetin Inhibits Lipopolysaccharide-Induced Inflammatory Response in Human Umbilical Vein Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Lei Song

    2016-11-01

    Full Text Available Background/Aim: Crocetin is a readily bioavailable and bioactive compound extracted from Saffron. Previous studies indicated its various biomedical properties including antioxidant and anti-coagulation potencies. However, its effect on inflammation, notably within the cardiovascular system, has not been investigated yet. In the present study, we utilized human umbilical vein endothelial cell (HUVEC to elucidate the effect of Crocetin on vascular inflammation. Methods: Cell viability and toxicity were evaluated by MTT and Lactate dehydrogenase (LDH assay, respectively. Pro-inflammatory chemokine Monocyte Chemoattractant Protein-1 (MCP-1 and Interleukin-8 (IL-8 expressions were determined by RT-PCR and ELISA. With fluorescence labeled U937 cells, we examined immune cell adhesion to the inflamed HUVEC in vitro, which was further confirmed by the H&E staining in the murine subcutaneous endothelium in vivo. Results: Upon Lipopolysaccharide (LPS-induced inflammatory response in HUVECs, Crocetin ameliorated cell cytotoxicity, suppressed MCP-1 and IL-8 expressions through blocking NF-κB p65 signaling transduction. Moreover, Crocetin inhibited immune cells adhesion and infiltration to inflamed endothelium, which is a key step in inflammatory vascular injury. Conclusions: These findings suggest that Crocetin, a natural herb extract, is a potent suppressor of vascular endothelial inflammation.

  14. The cytochrome P450 epoxygenase pathway regulates the hepatic inflammatory response in fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Robert N Schuck

    Full Text Available Fatty liver disease is an emerging public health problem without effective therapies, and chronic hepatic inflammation is a key pathologic mediator in its progression. Cytochrome P450 (CYP epoxygenases metabolize arachidonic acid to biologically active epoxyeicosatrienoic acids (EETs, which have potent anti-inflammatory effects. Although promoting the effects of EETs elicits anti-inflammatory and protective effects in the cardiovascular system, the contribution of CYP-derived EETs to the regulation of fatty liver disease-associated inflammation and injury is unknown. Using the atherogenic diet model of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH, our studies demonstrated that induction of fatty liver disease significantly and preferentially suppresses hepatic CYP epoxygenase expression and activity, and both hepatic and circulating levels of EETs in mice. Furthermore, mice with targeted disruption of Ephx2 (the gene encoding soluble epoxide hydrolase exhibited restored hepatic and circulating EET levels and a significantly attenuated induction of hepatic inflammation and injury. Collectively, these data suggest that suppression of hepatic CYP-mediated EET biosynthesis is an important pathological consequence of fatty liver disease-associated inflammation, and that the CYP epoxygenase pathway is a central regulator of the hepatic inflammatory response in NAFLD/NASH. Future studies investigating the utility of therapeutic strategies that promote the effects of CYP-derived EETs in NAFLD/NASH are warranted.

  15. Melatonin modulates inflammatory response and suppresses burn-induced apoptotic injury

    Directory of Open Access Journals (Sweden)

    Ganka Bekyarova

    2017-04-01

    Full Text Available Introduction: Melatonin, the principal secretory product of the pineal gland, has antioxidant functions as a potent antioxidant and free radical scavenger. Objectives of the present study were to investigate the effect of melatonin against inflammatory response, burn-induced oxidative damage and apoptotic changes of rat liver. Methods: Melatonin (10 mg /kg, i.p. was applied immediately after 30% of total body surface area (TBSA burns on male Wistar rats. The level of malondialdehyde (MDA as a marker of an oxidative stress was quantified by thiobarbituric method. Hepatic TNFα and IL-10 as inflammatory markers were assayed by ELISA. Using light immunоchistochemistry the expression Ki67 proliferative marker was investigated. Results: Hepatic MDA and TNF-α levels increased significantly following burns without any change in IL-10 level. Intracellular vacuolization, hepatic cell degeneration and apoptosis occurred in rats after burns. The number of apoptotic cells was increased whereas no significant increase in Ki67 proliferative marker. Melatonin decreased the MDA and TNF-α content and increased the IL-10 level. It also limited the degenerative changes and formation of apoptotic cells in rat liver but did not increase expression of the marker of proliferation. In conclusion, our data show that melatonin relieves burn-induced hepatic damage associated with modulation of the proinflammatory/anti-inflammatory balance, mitigation of lipid peroxidation and hepatic apoptosis.

  16. Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response.

    Science.gov (United States)

    Cai, Shi-Ying; Ouyang, Xinshou; Chen, Yonglin; Soroka, Carol J; Wang, Juxian; Mennone, Albert; Wang, Yucheng; Mehal, Wajahat Z; Jain, Dhanpat; Boyer, James L

    2017-03-09

    Mechanisms of bile acid-induced (BA-induced) liver injury in cholestasis are controversial, limiting development of new therapies. We examined how BAs initiate liver injury using isolated liver cells from humans and mice and in-vivo mouse models. At pathophysiologic concentrations, BAs induced proinflammatory cytokine expression in mouse and human hepatocytes, but not in nonparenchymal cells or cholangiocytes. These hepatocyte-specific cytokines stimulated neutrophil chemotaxis. Inflammatory injury was mitigated in Ccl2(-/-) mice treated with BA or after bile duct ligation, where less hepatic infiltration of neutrophils was detected. Neutrophils in periportal areas of livers from cholestatic patients also correlated with elevations in their serum aminotransferases. This liver-specific inflammatory response required BA entry into hepatocytes via basolateral transporter Ntcp. Pathophysiologic levels of BAs induced markers of ER stress and mitochondrial damage in mouse hepatocytes. Chemokine induction by BAs was reduced in hepatocytes from Tlr9(-/-) mice, while liver injury was diminished both in conventional and hepatocyte-specific Tlr9(-/-) mice, confirming a role for Tlr9 in BA-induced liver injury. These findings reveal potentially novel mechanisms whereby BAs elicit a hepatocyte-specific cytokine-induced inflammatory liver injury that involves innate immunity and point to likely novel pathways for treating cholestatic liver disease.

  17. Magnesium supplement promotes sciatic nerve regeneration and down-regulates inflammatory response.

    Science.gov (United States)

    Pan, Hung-Chuan; Sheu, Meei-Ling; Su, Hong-Lin; Chen, Ying-Ju; Chen, Chun-Jung; Yang, Dar-Yu; Chiu, Wen-Ta; Cheng, Fu-Chou

    2011-06-01

    Magnesium (Mg) supplements have been shown to significantly improve functional recovery in various neurological disorders. The essential benefits of Mg supplementation in peripheral nerve disorders have not been elucidated yet. The effect and mechanism of Mg supplementation on a sciatic nerve crush injury model was investigated. Sciatic nerve injury was induced in mice by crushing the left sciatic nerve. Mice were randomly divided into three groups with low-, basal- or high-Mg diets (corresponding to 10, 100 or 200% Mg of the basal diet). Neurobehavioral, electrophysiological and regeneration marker studies were conducted to explore nerve regeneration. First, a high Mg diet significantly increased plasma and nerve tissue Mg concentrations. In addition, Mg supplementation improved neurobehavioral, electrophysiological functions, enhanced regeneration marker, and reduced deposits of inflammatory cells as well as expression of inflammatory cytokines. Furthermore, reduced Schwann cell apoptosis was in line with the significant expression of bcl-2, bcl-X(L) and down-regulated expression of active caspase-3 and cytochrome C. In summary, improved neurological function recovery and enhanced nerve regeneration were found in mice with a sciatic nerve injury that were fed a high- Mg diet, and Schwann cells may have been rescued from apoptosis by the suppression of inflammatory responses.

  18. Effects of equine metabolic syndrome on inflammatory responses of horses to intravenous lipopolysaccharide infusion.

    Science.gov (United States)

    Tadros, Elizabeth M; Frank, Nicholas; Donnell, Robert L

    2013-07-01

    To test the hypothesis that inflammatory responses to endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS). Animals-6 healthy horses and 6 horses with EMS. Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline data were obtained 30 minutes before each infusion. After infusion, a physical examination was performed hourly for 9 hours and at 15 and 21 hours; a whole blood sample was collected at 30, 60, 90, 120, 180, and 240 minutes for assessment of inflammatory cytokine gene expression. Liver biopsy was performed between 240 and 360 minutes after infusion. Results-Following lipopolysaccharide infusion in healthy horses and horses with EMS, mean rectal temperature, heart rate, and respiratory rate increased, compared with baseline findings, as did whole blood gene expression of interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α. The magnitude of blood cytokine responses did not differ between groups, but increased expression of IL-6, IL-8, IL-10, and tumor necrosis factor-α persisted for longer periods in EMS-affected horses. Lipopolysaccharide infusion increased liver tissue gene expressions of IL-6 in healthy horses and IL-8 in both healthy and EMS-affected horses, but these gene expressions did not differ between groups. Results supported the hypothesis that EMS affects horses' inflammatory responses to endotoxin by prolonging cytokine expression in circulating leukocytes. These findings are relevant to the association between obesity and laminitis in horses with EMS.

  19. Time-course of changes in inflammatory and performance responses following a soccer game.

    Science.gov (United States)

    Ispirlidis, Ioannis; Fatouros, Ioannis G; Jamurtas, Athanasios Z; Nikolaidis, Michalis G; Michailidis, Ioannis; Douroudos, Ioannis; Margonis, Konstantinos; Chatzinikolaou, Athanasios; Kalistratos, Elias; Katrabasas, Ioannis; Alexiou, Vassilios; Taxildaris, Kiriakos

    2008-09-01

    : To study the effects of a single soccer game on indices of performance, muscle damage, and inflammation during a 6-day recovery period. : Participants were assigned to either an experimental group (E, played in the game; n = 14) or a control group (C, did not participate in the game; n = 10). : Data were collected on a soccer field and at the Physical Education and Sports Science laboratory of the Democritus University of Thrace before and after the soccer game. : Twenty-four elite male soccer players (age, 20.1 +/- 0.8 years; height, 1.78 +/- 0.08 m; weight, 75.2 +/- 6.8 kg). : Muscle strength, vertical jumping, speed, DOMS, muscle swelling, leukocyte count, creatine kinase (CK), lactate dehydrogenase (LDH), C-reactive protein (CRP), cortisol, testosterone, cytokines IL-6 and IL-1b, thioburbituric acid-reactive substances (TBARS), protein carbnyls (PC), and uric acid (UA). : Performance deteriorated 1 to 4 days post-game. An acute-phase inflammatory response consisted of a post-game peak of leukocyte count, cytokines, and cortisol, a 24-hour peak of CRP, TBARS, and DOMS, a 48-hour peak of CK, LDH, and PC, and a 72-hour peak of uric acid. : A single soccer game induces short-term muscle damage and marked but transient inflammatory responses. Anaerobic performance seems to deteriorate for as long as 72-hour post-game. The acute phase inflammatory response in soccer appears to follow the same pattern as in other forms of exercise. These results clearly indicate the need of sufficient recovery for elite soccer players after a game.

  20. Accelerated resolution of inflammation underlies sex differences in inflammatory responses in humans.

    Science.gov (United States)

    Rathod, Krishnaraj S; Kapil, Vikas; Velmurugan, Shanti; Khambata, Rayomand S; Siddique, Umme; Khan, Saima; Van Eijl, Sven; Gee, Lorna C; Bansal, Jascharanpreet; Pitrola, Kavi; Shaw, Christopher; D'Acquisto, Fulvio; Colas, Romain A; Marelli-Berg, Federica; Dalli, Jesmond; Ahluwalia, Amrita

    2017-01-03

    Cardiovascular disease occurs at lower incidence in premenopausal females compared with age-matched males. This variation may be linked to sex differences in inflammation. We prospectively investigated whether inflammation and components of the inflammatory response are altered in females compared with males. We performed 2 clinical studies in healthy volunteers. In 12 men and 12 women, we assessed systemic inflammatory markers and vascular function using brachial artery flow-mediated dilation (FMD). In a further 8 volunteers of each sex, we assessed FMD response to glyceryl trinitrate (GTN) at baseline and at 8 hours and 32 hours after typhoid vaccine. In a separate study in 16 men and 16 women, we measured inflammatory exudate mediators and cellular recruitment in cantharidin-induced skin blisters at 24 and 72 hours. Typhoid vaccine induced mild systemic inflammation at 8 hours, reflected by increased white cell count in both sexes. Although neutrophil numbers at baseline and 8 hours were greater in females, the neutrophils were less activated. Systemic inflammation caused a decrease in FMD in males, but an increase in females, at 8 hours. In contrast, GTN response was not altered in either sex after vaccine. At 24 hours, cantharidin formed blisters of similar volume in both sexes; however, at 72 hours, blisters had only resolved in females. Monocyte and leukocyte counts were reduced, and the activation state of all major leukocytes was lower, in blisters of females. This was associated with enhanced levels of the resolving lipids, particularly D-resolvin. Our findings suggest that female sex protects against systemic inflammation-induced endothelial dysfunction. This effect is likely due to accelerated resolution of inflammation compared with males, specifically via neutrophils, mediated by an elevation of the D-resolvin pathway. ClinicalTrials.gov NCT01582321 and NRES: City Road and Hampstead Ethics Committee: 11/LO/2038. The authors were funded by multiple

  1. Apoptosis and pro-inflammatory cytokine response of mast cells induced by influenza A viruses.

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    Bo Liu

    Full Text Available The pathogenesis of the influenza A virus has been investigated heavily, and both the inflammatory response and apoptosis have been found to have a definitive role in this process. The results of studies performed by the present and other groups have indicated that mast cells may play a role in the severity of the disease. To further investigate cellular responses to influenza A virus infection, apoptosis and inflammatory response were studied in mouse mastocytoma cell line P815. This is the first study to demonstrate that H1N1 (A/WSN/33, H5N1 (A/Chicken/Henan/1/04, and H7N2 (A/Chicken/Hebei/2/02 influenza viruses can induce mast cell apoptosis. They were found to do this mainly through the mitochondria/cytochrome c-mediated intrinsic pathway, and the activation of caspase 8-mediated extrinsic pathway was here found to be weak. Two pro-apoptotic Bcl-2 homology domain 3 (BH3 -only molecules Bim and Puma appeared to be involved in the apoptotic pathways. When virus-induced apoptosis was inhibited in P815 cells using pan-caspase (Z-VAD-fmk and caspase-9 (Z-LEHD-fmk inhibitors, the replication of these three subtypes of viruses was suppressed and the secretions of pro-inflammatory cytokines and chemokines, including IL-6, IL-18, TNF-α, and MCP-1, decreased. The results of this study may further understanding of the role of mast cells in host defense and pathogenesis of influenza virus. They may also facilitate the development of novel therapeutic aids against influenza virus infection.

  2. Cerebral inflammatory response and predictors of admission clinical grade after aneurysmal subarachnoid hemorrhage.

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    Hanafy, Khalid A; Morgan Stuart, R; Fernandez, Luis; Schmidt, J Michael; Claassen, Jan; Lee, Kiwon; Sander Connolly, E; Mayer, Stephan A; Badjatia, Neeraj

    2010-01-01

    Poor admission clinical grade is the most important determinant of outcome after aneurysmal subarachnoid hemorrhage (aSAH); however, little attention has been focused on independent predictors of poor admission clinical grade. We hypothesized that the cerebral inflammatory response initiated at the time of aneurysm rupture contributes to ultra-early brain injury and poor admission clinical grade. We sought to identify factors known to contribute to cerebral inflammation as well as markers of cerebral dysfunction that were associated with poor admission clinical grade. Between 1997 and 2008, 850 consecutive SAH patients were enrolled in our prospective database. Demographic data, physiological parameters, and location and volume of blood were recorded. After univariate analysis, significant variables were entered into a logistic regression model to identify significant associations with poor admission clinical grade (Hunt-Hess grade 4-5). Independent predictors of poor admission grade included a SAH sum score >15/30 (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.5-3.6), an intraventricular hemorrhage sum score >1/12 (OR 3.1, 95% CI 2.1-4.8), aneurysm size >10mm (OR 1.7, 95% CI 1.1-2.6), body temperature 38.3 degrees C (OR 2.5, 95% CI 1.1-5.4), and hyperglycemia >200mg/dL (OR 2.7, 95% CI 1.6-4.5). In a large, consecutive series of prospectively enrolled patients with SAH, the inflammatory response at the time of aneurysm rupture, as reflected by the volume and location of the hemoglobin burden, hyperthermia, and perturbed glucose metabolism, independently predicts poor admission Hunt-Hess grade. Strategies for mitigating the inflammatory response to aneurysmal rupture in the hyper-acute setting may improve the admission clinical grade, which may in turn improve outcomes. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  3. The human metapneumovirus matrix protein stimulates the inflammatory immune response in vitro.

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    Audrey Bagnaud-Baule

    Full Text Available Each year, during winter months, human Metapneumovirus (hMPV is associated with epidemics of bronchiolitis resulting in the hospitalization of many infants. Bronchiolitis is an acute illness of the lower respiratory tract with a consequent inflammation of the bronchioles. The rapid onset of inflammation suggests the innate immune response may have a role to play in the pathogenesis of this hMPV infection. Since, the matrix protein is one of the most abundant proteins in the Paramyxoviridae family virion, we hypothesized that the inflammatory modulation observed in hMPV infected patients may be partly associated with the matrix protein (M-hMPV response. By western blot analysis, we detected a soluble form of M-hMPV released from hMPV infected cell as well as from M-hMPV transfected HEK 293T cells suggesting that M-hMPV may be directly in contact with antigen presenting cells (APCs during the course of infection. Moreover, flow cytometry and confocal microscopy allowed determining that M-hMPV was taken up by dendritic cells (moDCs and macrophages inducing their activation. Furthermore, these moDCs enter into a maturation process inducing the secretion of a broad range of inflammatory cytokines when exposed to M-hMPV. Additionally, M-hMPV activated DCs were shown to stimulate IL-2 and IFN-γ production by allogeneic T lymphocytes. This M-hMPV-mediated activation and antigen presentation of APCs may in part explain the marked inflammatory immune response observed in pathology induced by hMPV in patients.

  4. IκBζ Regulates Human Monocyte Pro-Inflammatory Responses Induced by Streptococcus pneumoniae

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    Sundaram, Kruthika; Rahman, Mohd. Akhlakur; Mitra, Srabani; Knoell, Daren L.; Woodiga, Shireen A.; King, Samantha J.

    2016-01-01

    Pneumococcal lung infections represent a major cause of death worldwide. Single nucleotide polymorphisms (SNPs) in the NFKBIZ gene, encoding the transcription factor IκBζ, are associated with increased susceptibility to invasive pneumococcal disease. We hence analyzed how IκBζ might regulate inflammatory responses to pneumococcal infection. We first demonstrate that IκBζ is expressed in human blood monocytes but not in bronchial epithelial cells, in response to wild type pneumococcal strain D39. D39 transiently induced IκBζ in a dose dependent manner, with subsequent induction of downstream molecules involved in host defense. Of these molecules, IκBζ knockdown reduced the expression of IL-6 and GMCSF. Furthermore, IκBζ overexpression increased the activity of IL-6 and GMCSF promoters, supporting the knockdown findings. Pneumococci lacking either pneumolysin or capsule still induced IκBζ. While inhibition of TLR1/TLR2 blocked D39 induced IκBζ expression, TLR4 inhibition did not. Blockade of p38 MAP kinase and NFκB suppressed D39 induced IκBζ. Overall, our data demonstrates that IκBζ regulates monocyte inflammatory responses to Streptococcus pneumoniae by promoting the production of IL-6 and GMCSF. PMID:27597997

  5. Impact of Mycotoxins Secreted by Aspergillus Molds on the Inflammatory Response of Human Corneal Epithelial Cells

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    Yélian Marc Bossou

    2017-06-01

    Full Text Available Exposure to molds and mycotoxins not only contributes to the onset of respiratory disease, it also affects the ocular surface. Very few published studies concern the evaluation of the effect of mycotoxin exposure on ocular cells. The present study investigates the effects of aflatoxin B1 (AFB1 and gliotoxin, two mycotoxins secreted by Aspergillus molds, on the biological activity of the human corneal epithelial (HCE cells. After 24, 48, and 72 h of exposure, cellular viability and inflammatory response were assessed. Both endpoint cell viability colorimetric assays and continuous cell impedance measurements, providing noninvasive real-time assessment of the effect on cells, were performed. Cytokine gene expression and interleukin-8 release were quantified. Gliotoxin appeared more cytotoxic than AFB1 but, at the same time, led to a lower increase of the inflammatory response reflecting its immunosuppressive properties. Real-time cell impedance measurement showed a distinct profile of cytotoxicity for both mycotoxins. HCE cells appeared to be a well-suited in vitro model to study ocular surface reactivity following biological contaminant exposure. Low, but persistent inflammation, caused by environmental factors, such as fungal toxins, leads to irritation and sensitization, and could be responsible for allergic manifestations which, in turn, could lead to mucosal hyper-reactivity.

  6. 3D culture broadly regulates tumor cell hypoxia response and angiogenesis via pro-inflammatory pathways.

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    DelNero, Peter; Lane, Maureen; Verbridge, Scott S; Kwee, Brian; Kermani, Pouneh; Hempstead, Barbara; Stroock, Abraham; Fischbach, Claudia

    2015-07-01

    Oxygen status and tissue dimensionality are critical determinants of tumor angiogenesis, a hallmark of cancer and an enduring target for therapeutic intervention. However, it is unclear how these microenvironmental conditions interact to promote neovascularization, due in part to a lack of comprehensive, unbiased data sets describing tumor cell gene expression as a function of oxygen levels within three-dimensional (3D) culture. Here, we utilized alginate-based, oxygen-controlled 3D tumor models to study the interdependence of culture context and the hypoxia response. Microarray gene expression analysis of tumor cells cultured in 2D versus 3D under ambient or hypoxic conditions revealed striking interdependence between culture dimensionality and hypoxia response, which was mediated in part by pro-inflammatory signaling pathways. In particular, interleukin-8 (IL-8) emerged as a major player in the microenvironmental regulation of the hypoxia program. Notably, this interaction between dimensionality and oxygen status via IL-8 increased angiogenic sprouting in a 3D endothelial invasion assay. Taken together, our data suggest that pro-inflammatory pathways are critical regulators of tumor hypoxia response within 3D environments that ultimately impact tumor angiogenesis, potentially providing important therapeutic targets. Furthermore, these results highlight the importance of pathologically relevant tissue culture models to study the complex physical and chemical processes by which the cancer microenvironment mediates new vessel formation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Systemic inflammatory response syndrome as a predictor of anastomotic leakage after esophagectomy.

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    Tsujimoto, Hironori; Ono, Satoshi; Takahata, Risa; Hiraki, Shuichi; Yaguchi, Yoshihisa; Kumano, Isao; Matsumoto, Yusuke; Yoshida, Kazumichi; Aiko, Satoshi; Ichikura, Takashi; Yamamoto, Junji; Hase, Kazuo

    2012-01-01

    Esophageal anastomotic leakage is still a major cause of morbidity and mortality after esophagectomy. We conducted this study to elucidate how anastomotic leakage affects the systemic inflammatory response syndrome (SIRS) criteria. The subjects of this retrospective study were 61 patients who underwent esophagectomy. We evaluated their preoperative status, the surgical procedures, and postoperative systemic response, including white blood cell count, heart rate, respiratory rate, body temperature, and laboratory data up to postoperative day (POD) 4. Anastomotic leakage developed in nine patients (14.8%) and was found on POD 7 on average. These patients had a significantly longer hospital stay than those without leakage. Although no difference was observed in postoperative changes of any of the SIRS criteria, the postoperative incidence of SIRS was significantly higher in the patients with anastomotic leakage on POD 4. The number of positive criteria for SIRS was also significantly higher in patients with anastomotic leakage than in those without leakage on PODs 3 and 4. The SIRS scoring system is valuable for evaluating the severity of systemic inflammatory response caused by anastomosis leakage, and may serve as an indicator for prompt management.

  8. The quantification of cellular viability and inflammatory response to stainless steel alloys.

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    Bailey, LeeAnn O; Lippiatt, Sherry; Biancanello, Frank S; Ridder, Stephen D; Washburn, Newell R

    2005-09-01

    The biocompatibility of metallic alloys is critical to the success of many orthopedic therapies. Corrosion resistance and the immune response of the body to wear debris products ultimately determine the performance of these devices. The establishment of quantitative tests of biocompatibility is an important issue for biomaterials development. We have developed an in vitro model to measure the pro-inflammatory cytokine production and in this study investigated the cellular responses induced by nitrogenated and 316L stainless steel alloys in both particulate and solid form. We utilized a murine macrophage cell line, RAW 264.7, to characterize and compare the mRNA profiles of TNF-alpha and IL-1beta in these cells using real time-polymerase chain reaction (RT-PCR). Fluorescence microscopy and flow cytometry were used to probe the viability of the population and to examine the apoptotic pathway. The goals of this work were to develop improved measurement methods for the quantification of cellular inflammatory responses to biomaterials and to obtain data that leads to an enhanced understanding of the ways in which the body responds to biomaterials. Using these techniques, we observed evidence for an association between the upregulation of IL-1beta and reversible apoptosis, and the upregulation of TNF-alpha and irreversible apoptosis.

  9. Characterization of the antiviral and inflammatory responses against Nipah virus in endothelial cells and neurons.

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    Lo, Michael K; Miller, David; Aljofan, Mohammad; Mungall, Bruce A; Rollin, Pierre E; Bellini, William J; Rota, Paul A

    2010-08-15

    Nipah virus (NiV) is a highly pathogenic paramyxovirus which causes fatal encephalitis in up to 75% of infected humans. Endothelial cells and neurons are important cellular targets in the pathogenesis of this disease. In this study, viral replication and the innate immune responses to NiV in these cell types were measured. NiV infected endothelial cells generated a functionally robust IFN-beta response, which correlated with localization of the NiV W protein to the cytoplasm. There was no antiviral response detected in infected neuronal cells. NiV infection of endothelial cells induced a significant increase in secreted inflammatory chemokines, which corresponded with the increased ability of infected cell supernatants to induce monocyte and T-lymphocyte chemotaxis. These results suggest that pro-inflammatory chemokines produced by NiV infected primary endothelial cells in vitro is consistent with the prominent vasculitis observed in infections, and provide initial molecular insights into the pathogenesis of NiV in physiologically relevant cells types.

  10. SOCS Proteins as Regulators of Inflammatory Responses Induced by Bacterial Infections: A Review

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    Skyla A. Duncan

    2017-12-01

    Full Text Available Severe bacterial infections can lead to both acute and chronic inflammatory conditions. Innate immunity is the first defense mechanism employed against invading bacterial pathogens through the recognition of conserved molecular patterns on bacteria by pattern recognition receptors (PRRs, especially the toll-like receptors (TLRs. TLRs recognize distinct pathogen-associated molecular patterns (PAMPs that play a critical role in innate immune responses by inducing the expression of several inflammatory genes. Thus, activation of immune cells is regulated by cytokines that use the Janus kinase/signal transducers and activators of transcription (JAK/STAT signaling pathway and microbial recognition by TLRs. This system is tightly controlled by various endogenous molecules to allow for an appropriately regulated and safe host immune response to infections. Suppressor of cytokine signaling (SOCS family of proteins is one of the central regulators of microbial pathogen-induced signaling of cytokines, principally through the inhibition of the activation of JAK/STAT signaling cascades. This review provides recent knowledge regarding the role of SOCS proteins during bacterial infections, with an emphasis on the mechanisms involved in their induction and regulation of antibacterial immune responses. Furthermore, the implication of SOCS proteins in diverse processes of bacteria to escape host defenses and in the outcome of bacterial infections are discussed, as well as the possibilities offered by these proteins for future targeted antimicrobial therapies.

  11. Antibody and inflammatory responses in laying hens with experimental primary infections of Ascaridia galli.

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    Marcos-Atxutegi, C; Gandolfi, B; Arangüena, T; Sepúlveda, R; Arévalo, M; Simón, F

    2009-04-06

    Ascaridia galli, an intestinal nematode that affects hens and other domestic and wild birds, causes economic losses in avian exploitations. The present work shows that A. galli stimulates a strong antibody response as well as an intense inflammatory reaction, in the intestinal mucous of experimentally infected Lohmann Brown laying hens. IgG antibodies against soluble extracts of A. galli embrionated eggs and adult worms, were detected in both blood and yolks eggs from infected hens during a period of 105 days after the infection. This indicates that hens transfer to their offspring a part of the IgG antibodies produced when they become infected. The antigens responsible for the stimulation of specific IgG were molecules of 30-34, 44-54 and 58-90 kDa, while in the yolk eggs of infected hens a reactivity directed against antigens of molecular weight (M(w)) lower than 50 kDa was detected. Histology revealed traumatic lesions with leukocyte infiltration, and inflammation of the intestinal wall of the infected hens after 105 days of initial infection. The possible influence of the immune and inflammatory response on the population dynamics of the parasite is discussed.

  12. Histamine Induces Bovine Rumen Epithelial Cell Inflammatory Response via NF-κB Pathway.

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    Sun, Xudong; Yuan, Xue; Chen, Liang; Wang, Tingting; Wang, Zhe; Sun, Guoquan; Li, Xiaobing; Li, Xinwei; Liu, Guowen

    2017-01-01

    Subacute ruminal acidosis (SARA) is a common disease in high-producing lactating cows. Rumenitis is the initial insult of SARA and is associated with the high concentrations of histamine produced in the rumen of dairy cows during SARA. However, the exact mechanism remains unclear. The objective of the current study is to investigate whether histamine induces inflammation of rumen epithelial cells and the underlying mechanism of this process. Bovine rumen epithelial cells were cultured and treated with different concentrations of histamine and pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) cultured in different pH medium (pH 7.2 or 5.5). qRT-PCR, Western-blotting, ELISA and immunocytofluorescence were used to evaluate whether histamine activated the NF-κB pathway and inflammatory cytokines. The results showed that histamine significantly increased the activity of IKK β and the phosphorylation levels of IκB α, as well as upregulated the mRNA and protein expression levels of NF-κB p65 in the rumen epithelial cells cultured in neutral (pH=7.2) and acidic (pH=5.5) medium. Furthermore, histamine treatment also significantly increased the transcriptional activity of NF-κB p65. High expression and transcriptional activity of NF-κB p65 significantly increased the mRNA expressions and concentrations of inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and interleukin 1 beta (IL-1β), thereby inducing the inflammatory response in bovine rumen epithelial cells. However, inhibition of NF-κB p65 by PDTC significantly decreased the expressions and concentrations of the inflammatory cytokines induced by histamine in the rumen epithelial cells cultured in the neutral and acidic medium. The present data indicate that histamine induces the inflammatory response of bovine rumen epithelial cells through the NF-κB pathway. © 2017 The Author(s). Published by S. Karger AG, Basel.

  13. Diminazene aceturate (Berenil modulates the host cellular and inflammatory responses to Trypanosoma congolense infection.

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    Shiby Kuriakose

    Full Text Available BACKGROUND: Trypanosoma congolense are extracellular and intravascular blood parasites that cause debilitating acute or chronic disease in cattle and other domestic animals. Diminazene aceturate (Berenil has been widely used as a chemotherapeutic agent for trypanosomiasis in livestock since 1955. As in livestock, treatment of infected highly susceptible BALB/c mice with Berenil leads to rapid control of parasitemia and survival from an otherwise lethal infection. The molecular and biochemical mechanisms of action of Berenil are still not very well defined and its effect on the host immune system has remained relatively unstudied. Here, we investigated whether Berenil has, in addition to its trypanolytic effect, a modulatory effect on the host immune response to Trypanosoma congolense. METHODOLOGY/PRINCIPAL FINDINGS: BALB/c and C57BL/6 mice were infected intraperitoneally with T. congolense, treated with Berenil and the expression of CD25 and FoxP3 on splenic cells was assessed directly ex vivo. In addition, serum levels and spontaneous and LPS-induced production of pro-inflammatory cytokines by splenic and hepatic CD11b⁺ cells were determined by ELISA. Berenil treatment significantly reduced the percentages of CD25⁺ cells, a concomitant reduction in the percentage of regulatory (CD4⁺Foxp3⁺ T cells and a striking reduction in serum levels of disease exacerbating pro-inflammatory cytokines including IL-6, IL-12, TNF and IFN-γ. Furthermore, Berenil treatment significantly suppressed spontaneous and LPS-induced production of inflammatory cytokines by splenic and liver macrophages and significantly ameliorated LPS-induced septic shock and the associated cytokine storm. CONCLUSIONS/SIGNIFICANCE: Collectively, these results provide evidence that in addition to its direct trypanolytic effect, Berenil also modulates the host immune response to the parasite in a manner that dampen excessive immune activation and production of pathology

  14. Recombinant human erythropoietin reduces plasminogen activator inhibitor and ameliorates pro-inflammatory responses following trauma

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    M Mojtahedzadeh

    2011-05-01

    Full Text Available "n  "n Background and the purpose of the study: Besides its hematopoietic effects, erythropoietin (EPO by mobilization of iron and modulation of some inflammatory cytokines has antioxidant and anti-inflammatory properties. The purpose of this study was to evaluate these effects of erythropoietin and its impact on organ function in traumatized patients. "n Methods: Twenty-six ICU-admitted traumatized patients within 24 hrs after trauma were randomly assigned to the EPO (received EPO, 300 units/Kg/day and Control (not received EPO groups. The inflammatory biomarkers including Tumor Necrosis Factor alpha (TNF-α, Interleukin 1 (IL-1, Plasminogen Activator Inhibitor 1 (PAI-1 and Nitrotyrosine were recorded at the admission, 3, 6 and 9 days thereafter. Acute Physiology and Chronic Health Evaluation (APACHE II and Sequential Organ Failure Assessment (SOFA scores were also recorded. "n Results: Among 12 patients (EPO group TNF-α level at the day of 9 (P=0.046, and within EPO group at the days of 3 (P=0.026 ameliorate, 6 (P=0.016, and 9 (P=0.052 were significantly lowered. Level of IL-1 and PAI-1 decreased significantly at days of 3, 6 and 9 post intervention. Also there were significant differences between two groups in the SOFA score during three measured time intervals (the first, third and seventh days. "n Conclusion: From the results of this study it seems that injection of erythrocyte stimulating agent is well tolerated and inhibits the inflammatory response and oxidative stress following trauma.

  15. BMPRII influences the response of pulmonary microvascular endothelial cells to inflammatory mediators.

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    Vengethasamy, Leanda; Hautefort, Aurélie; Tielemans, Birger; Belge, Catharina; Perros, Frédéric; Verleden, Stijn; Fadel, Elie; Van Raemdonck, Dirk; Delcroix, Marion; Quarck, Rozenn

    2016-11-01

    Mutations in the bone morphogenetic protein receptor (BMPR2) gene have been observed in 70 % of patients with heritable pulmonary arterial hypertension (HPAH) and in 11-40 % with idiopathic PAH (IPAH). However, carriers of a BMPR2 mutation have only 20 % risk of developing PAH. Since inflammatory mediators are increased and predict survival in PAH, they could act as a second hit inducing the development of pulmonary hypertension in BMPR2 mutation carriers. Our specific aim was to determine whether inflammatory mediators could contribute to pulmonary vascular cell dysfunction in PAH patients with and without a BMPR2 mutation. Pulmonary microvascular endothelial cells (PMEC) and arterial smooth muscle cells (PASMC) were isolated from lung parenchyma of transplanted PAH patients, carriers of a BMPR2 mutation or not, and from lobectomy patients or lung donors. The effects of CRP and TNFα on mitogenic activity, adhesiveness capacity, and expression of adhesion molecules were investigated in PMECs and PASMCs. PMECs from BMPR2 mutation carriers induced an increase in PASMC mitogenic activity; moreover, endothelin-1 secretion by PMECs from carriers was higher than by PMECs from non-carriers. Recruitment of monocytes by PMECs isolated from carriers was higher compared to PMECs from non-carriers and from controls, with an elevated ICAM-1 expression. CRP increased adhesion of monocytes to PMECs in carriers and non-carriers, and TNFα only in carriers. PMEC from BMPR2 mutation carriers have enhanced adhesiveness for monocytes in response to inflammatory mediators, suggesting that BMPR2 mutation could generate susceptibility to an inflammatory insult in PAH.

  16. Lactobacillus acidophilus alleviates platelet-activating factor-induced inflammatory responses in human intestinal epithelial cells.

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    Alip Borthakur

    Full Text Available Probiotics have been used as alternative prevention and therapy modalities in intestinal inflammatory disorders including inflammatory bowel diseases (IBD and necrotizing enterocolitis (NEC. Pathophysiology of IBD and NEC includes the production of diverse lipid mediators, including platelet-activating factor (PAF that mediate inflammatory responses in the disease. PAF is known to activate NF-κB, however, the mechanisms of PAF-induced inflammation are not fully defined. We have recently described a novel PAF-triggered pathway of NF-κB activation and IL-8 production in intestinal epithelial cells (IECs, requiring the pivotal role of the adaptor protein Bcl10 and its interactions with CARMA3 and MALT1. The current studies examined the potential role of the probiotic Lactobacillus acidophilus in reversing the PAF-induced, Bcl10-dependent NF-κB activation and IL-8 production in IECs. PAF treatment (5 µM×24 h of NCM460 and Caco-2 cells significantly increased nuclear p65 NF-κB levels and IL-8 secretion (2-3-fold, P<0.05, compared to control, which were blocked by pretreatment of the cells for 6 h with L. acidophilus (LA or its culture supernatant (CS, followed by continued treatments with PAF for 24 h. LA-CS also attenuated PAF-induced increase in Bcl10 mRNA and protein levels and Bcl10 promoter activity. LA-CS did not alter PAF-induced interaction of Bcl10 with CARMA3, but attenuated Bcl10 interaction with MALT1 and also PAF-induced ubiquitination of IKKγ. Efficacy of bacteria-free CS of LA in counteracting PAF-induced inflammatory cascade suggests that soluble factor(s in the CS of LA mediate these effects. These results define a novel mechanism by which probiotics counteract PAF-induced inflammation in IECs.

  17. Triggering of inflammasome by aggregated α-synuclein, an inflammatory response in synucleinopathies.

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    Gaia Codolo

    Full Text Available Parkinson's disease (PD is one of the most common neurodegenerative diseases. It is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta of the brain. Another feature is represented by the formation in these cells of inclusions called Lewy bodies (LB, principally constituted by fibrillar α-synuclein (αSyn. This protein is considered a key element in the aetiology of a group of neurodegenerative disorders termed synucleinopathies, which include PD, but the cellular and molecular mechanisms involved are not completely clear. It is established that the inflammatory process plays a crucial role in the pathogenesis and/or progression of PD; moreover, it is known that aggregated αSyn, released by neurons, activates microglia cells to produce pro-inflammatory mediators, such as IL-1β. IL-1β is one of the strongest pro-inflammatory cytokines; it is produced as an inactive mediator, and its maturation and activation requires inflammasome activation. In particular, the NLRP3 inflammasome is activated by a wide variety of stimuli, among which are crystallized and particulate material. In this work, we investigated the possibility that IL-1β production, induced by fibrillar αSyn, is involved the inflammasome activation. We demonstrated the competence of monomeric and fibrillar αSyn to induce synthesis of IL-1β, through TLR2 interaction; we found that the secretion of the mature cytokine was a peculiarity of the fibrillated protein. Moreover, we observed that the secretion of IL-1β involves NLRP3 inflammasome activation. The latter relies on the phagocytosis of fibrillar αSyn, followed by increased ROS production and cathepsin B release into the cytosol. Taken together, our data support the notion that fibrillar αSyn, likely released by neuronal degeneration, acts as an endogenous trigger inducing a strong inflammatory response in PD.

  18. Magnolol inhibits the inflammatory response in mouse mammary epithelial cells and a mouse mastitis model.

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    Wei, Wang; Dejie, Liang; Xiaojing, Song; Tiancheng, Wang; Yongguo, Cao; Zhengtao, Yang; Naisheng, Zhang

    2015-02-01

    Mastitis comprises an inflammation of the mammary gland, which is almost always linked with bacterial infection. The treatment of mastitis concerns antimicrobial substances, but not very successful. On the other hand, anti-inflammatory therapy with Chinese traditional medicine becomes an effective way for treating mastitis. Magnolol is a polyphenolic binaphthalene compound extracted from the stem bark of Magnolia sp., which has been shown to exert a potential for anti-inflammatory activity. The purpose of this study was to investigate the protective effects of magnolol on inflammation in lipopolysaccharide (LPS)-induced mastitis mouse model in vivo and the mechanism of this protective effects in LPS-stimulated mouse mammary epithelial cells (MMECs) in vitro. The damage of tissues was determined by histopathology and myeloperoxidase (MPO) assay. The expression of pro-inflammatory cytokines was determined by enzyme-linked immunosorbent assay (ELISA). Nuclear factor-kappa B (NF-κB), inhibitory kappa B (IκBα) protein, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and Toll-like receptor 4 (TLR4) were determined by Western blot. The results showed that magnolol significantly inhibit the LPS-induced TNF-α, IL-6, and IL-1β production both in vivo and vitro. Magnolol declined the phosphorylation of IκBα, p65, p38, ERK, and JNK in LPS-stimulated MMECs. Furthermore, magnolol inhibited the expression of TLR4 in LPS-stimulated MMECs. In vivo study, it was also observed that magnolol attenuated the damage of mastitis tissues in the mouse models. These findings demonstrated that magnolol attenuate LPS-stimulated inflammatory response by suppressing TLR4/NF-κB/mitogen-activated protein kinase (MAPK) signaling system. Thereby, magnolol may be a therapeutic agent against mastitis.

  19. Metformin activation of AMPK suppresses AGE-induced inflammatory response in hNSCs.

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    Chung, Ming-Min; Nicol, Christopher J; Cheng, Yi-Chuan; Lin, Kuan-Hung; Chen, Yen-Lin; Pei, Dee; Lin, Chien-Hung; Shih, Yi-Nuo; Yen, Chia-Hui; Chen, Shiang-Jiuun; Huang, Rong-Nan; Chiang, Ming-Chang

    2017-03-01

    A growing body of evidence suggests type 2 diabetes mellitus (T2DM) is linked to neurodegenerative diseases such as Alzheimer's disease (AD). Although the precise mechanisms remain unclear, T2DM may exacerbate neurodegenerative processes. AMP-activated protein kinase (AMPK) signaling is an evolutionary preserved pathway that is important during homeostatic energy biogenesis responses at both the cellular and whole-body levels. Metformin, a ubiquitously prescribed anti-diabetic drug, exerts its effects by AMPK activation. However, while the roles of AMPK as a metabolic mediator are generally well understood, its performance in neuroprotection and neurodegeneration are not yet well defined. Given hyperglycemia is accompanied by an accelerated rate of advanced glycosylation end product (AGE) formation, which is associated with the pathogenesis of diabetic neuronal impairment and, inflammatory response, clarification of the role of AMPK signaling in these processes is needed. Therefore, we tested the hypothesis that metformin, an AMPK activator, protects against diabetic AGE induced neuronal impairment in human neural stem cells (hNSCs). In the present study, hNSCs exposed to AGE had significantly reduced cell viability, which correlated with elevated inflammatory cytokine expression, such as IL-1α, IL-1β, IL-2, IL-6, IL-12 and TNF-α. Co-treatment with metformin significantly abrogated the AGE-mediated effects in hNSCs. In addition, metformin rescued the transcript and protein expression levels of acetyl-CoA carboxylase (ACC) and inhibitory kappa B kinase (IKK) in AGE-treated hNSCs. NF-κB is a transcription factor with a key role in the expression of a variety of genes involved in inflammatory responses, and metformin did prevent the AGE-mediated increase in NF-κB mRNA and protein levels in the hNSCs exposed to AGE. Indeed, co-treatment with metformin significantly restored inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) levels in AGE-treated h

  20. Granulomatous Inflammatory Response to a Microchip Implanted in a Dog for Eight Years.

    Science.gov (United States)

    Legallet, Claire; Mankin, Kelley Thieman; Spaulding, Kathy; Mansell, Joanne

    An 8 yr old neutered male springer spaniel dog was referred to Texas A&M University, College of Veterinary Medicine for a large, firm, fixed mass, located in the dorsal cervical tissue. The dog was otherwise healthy and had undergone microchip implantation approximately 8 yr prior. Radiographs, ultrasound, and microchip scanner confirmed the presence of a microchip within the mass. The microchip and associated mass were surgically excised, and histopathologic examination revealed granulomatous inflammation surrounding a cracked microchip. This case represents the first report of a granulomatous inflammatory response to a microchip 8 yr after implantation in a dog and highlights an important differential diagnosis.

  1. [MARKERS OF SYSTEMIC INFLAMMATORY RESPONSE IN PATIENTS OPERATED FOR COMPLICATIONS OF INFECTIOUS ENDOCARDITIS].

    Science.gov (United States)

    Petrova, O V; Shashin, S A; Tarasov, D G

    2015-01-01

    The study of markers of systemic inflammatory response in patients with infectious endocarditis showed that at admittance they had elevated blood C-reactive protein and ferritin levels while leukocyte count and fibrinogen content remained normal. C-reactive protein and ferritin levels increased on day 1 of the postoperative period and tended to grow further on day 3 when both parameters reached maximum values; they started to decrease on day 6 These data indicate that C-reactive protein and ferritin levels can be used to characterise the postoperative conditions of the patients including manifestations of systemic inflammation and outcome of surgical treatment.

  2. C1q binding to Dengue Virus inhibits infection of THP-1 and cellular inflammatory responses

    Science.gov (United States)

    Douradinha, Bruno; McBurney, Sean P.; de Melo, Klecia M. Soares; Smith, Amanda P.; Krishna, Neel K.; Barratt-Boyes, Simon M.; Evans, Jared D.; Nascimento, Eduardo J. M.; Marques, Ernesto T. A

    2014-01-01

    Summary Dengue virus infection elicits a spectrum of clinical presentations ranging from asymptomatic to severe disease. The mechanisms leading to severe dengue are not known, however it has been reported that the complement system is hyper-activated in severe dengue. Screening of complement proteins demonstrated that C1q, a pattern recognition molecule, can bind directly to Dengue Virus Envelope protein and to whole Dengue Virus serotype 2. Incubation of Dengue Virus serotype 2 with C1q prior to infection of THP-1 cells led to decreased virus infectivity and modulation of mRNA expression of immunoregulatory molecules suggesting reduced inflammatory responses. PMID:24246304

  3. Dietary tryptophan and methionine as modulators of European seabass (Dicentrarchus labrax) immune status and inflammatory response.

    Science.gov (United States)

    Machado, Marina; Azeredo, Rita; Díaz-Rosales, Patricia; Afonso, António; Peres, Helena; Oliva-Teles, Aires; Costas, Benjamín

    2015-02-01

    Amino acids regulate key metabolic pathways important to immune responses and their nutritional supply may increase synthesis of immune-related proteins. The present study aimed to evaluate the effects of dietary supplementation of tryptophan and methionine on European seabass (Dicentrarchus labrax) cellular and humoral status. The immunomodulatory effects of tryptophan and methionine during an inflammatory insult was also evaluated after intraperitoneal injection with inactivated Photobacterium damselae subsp. piscicida (Phdp). A practical isonitrogenous (45% crude protein) and isolipidic (16% crude fat) diets was formulated to include fish meal and a blend of plant feedstuffs as protein sources and fish oil as the main lipid source (CRL diet). Two other diets were formulated similar to the control but including L-tryptophan or L-methionine at ×2 the requirement level (diets TRP and MET, respectively). European seabass weighing 275 g were fed the experimental diets for a period of 15 days before being sampled (trial 1). Then, fish were subjected to a peritoneal inflammation by intraperitoneally injecting UV killed Phdp (10(6) colony forming units ml(-1)) and sampled following 4 and 24 h post-injection (trial 2). Fish injected with a saline solution served as control. The haematological profile, peripheral cell dynamics and several plasma immune parameters were determined in trials 1 and 2, whereas cell migration to the inflammatory focus was also determined in trial 2. MET positively affected European seabass immune status by improving the peripheral leucocyte response, complement activity and bactericidal capacity, a stronger cellular recruitment to the inflammatory focus, and higher plasma peroxidase and bactericidal activities. TRP also seemed to improve immunostimulation, as there was a trend to augment both cell-mediated immunity and humoral capacity. However, TRP failed to improve an inflammatory response, verified by a decrease in blood phagocyte numbers

  4. Influence of the blood bacterial load on the meningeal inflammatory response in Streptococcus pneumoniae meningitis

    DEFF Research Database (Denmark)

    Østergaard, C; O´Reilly, T; Brandt, C

    2006-01-01

    BACKGROUND: Despite bacteraemia is present in the majority of patients with pneumococcal, little is known about the influence of the systemic infection on the meningeal inflammatory response. METHODS: To explore the role of systemic infection on the meningeal inflammation, experimental meningitis...... levels in 153 pneumococcal meningitis patients with and without presence of bacteraemia. RESULTS: As designed, blood bacterial concentrations were significantly different among three experimental groups during the 16 hours study period (Kruskal Wallis test, P ... to the two other groups between 12-16 hours from time of infection (P meningitis, no significant difference in CSF WBC was observed between patients with or without bacteraemia at admission (n = 103, 1740...

  5. Impact of Thermal Injury on Wound Infiltration and the Dermal Inflammatory Response

    OpenAIRE

    Schwacha, Martin G.; Thobe, Bjoern M; Daniel, TanJanika; Hubbard, William J.

    2010-01-01

    Healing of the burn wound is a critical component of the burn patient's successful recovery. While inflammation is a critical component of the healing process, it is unknown whether the inflammatory response differs between non-burn and burn wounds. To study this, mice were subjected to major burn injury or sham procedure. Wound cells were collected by implantation of polyvinyl alcohol sponges beneath the burn site in injured mice or beneath uninjured skin in sham mice (i.e., non-burn wound)....

  6. SIDS pathogenesis: pathological findings indicate infection and inflammatory responses are involved.

    Science.gov (United States)

    Goldwater, Paul N

    2004-09-01

    This article explores the pathological evidence that supports the hypothesis that infection and inflammation are underlying mechanisms in SIDS. It reviews the pathological findings in relation to the risk factors reported for SIDS and compares these findings with other hypotheses suggested as causes of these unexplained deaths in infants. The roles of environmental factors and bacterial products such as soluble curlin detectable in SIDS sera in triggering cytokine cascades and aberrant inflammatory responses resulting in a toxic shock-like event are also explored. Areas for future research are outlined.

  7. Neutrophil contributions to the induction and regulation of the acute inflammatory response in teleost fish.

    Science.gov (United States)

    Havixbeck, Jeffrey J; Rieger, Aja M; Wong, Michael E; Hodgkinson, Jordan W; Barreda, Daniel R

    2016-02-01

    Neutrophils are essential to the acute inflammatory response, where they serve as the first line of defense against infiltrating pathogens. We report that, on receiving the necessary signals, teleost (Carassius auratus) neutrophils leave the hematopoietic kidney, enter into the circulation, and dominate the initial influx of cells into a site of inflammation. Unlike mammals, teleost neutrophils represent teleost macrophages and also played a role, at least in part, in the downregulation of macrophage reactive oxygen species production. Our results highlight the contributions of neutrophils to both the promotion and the regulation of teleost fish inflammation and provide added context for the evolution of this hematopoietic lineage. © Society for Leukocyte Biology.

  8. IMBALANCES IN PROTEIN METABOLISM IN CRITICAL CARE PATIENT WITH SYSTEMIC INFLAMMATORY RESPONSE SYNDROME AT ADMISSION IN INTENSIVE CARE UNIT.

    Science.gov (United States)

    Bouharras El Idrissi, Hicham; Molina López, Jorge; Pérez Moreno, Irene; Florea, Daniela Ioana; Lobo Támer, Gabriela; Herrera-Quintana, Lourdes; Pérez De La Cruz, Antonio; Rodríguez Elvira, Manuel; Planells Del Pozo, Elena María

    2015-12-01

    trauma and severe infections cause remarkable metabolic changes in patient with SIRS from an adaptive response aimed to control the underlying disease, repairing damaged tissue, and to synthesize substrates. If the attack is intense and sustained and the patient has a compromised nutritional status, can evolve into multiple organ failure and death. assessment of nutritional proteic status and the involvement of proteins and inflammatory factors in critically ill patients. multicenter observational analytical study in critical ill patients at the admission in ICU. patients showed disturbances in clinical nutritional parameters which confirm their hypercatabolic situation, showing malnutrition state at admission, where 42.9% had plasma levels below the reference prealbumin. Amino acid profile was situated below the reference values and 99% of patients had low plasma transferrin. Significant differences were observed in total protein, ferritin and transferrin parameters adjusted by CRP levels, being higher when patients presented high inflammation in the case of ferritin and the opposite for the rest of parameters. Adjusting APACHE and SOFA scores according to low, medium and high severity, results showed significant differences in creatinine, urea, and transferrin, being lower at high severity grade for the last one. critical illness is characterized by a high degree of stress and accelerated degradation of proteins that cause malnutrition, systemic inflammation and organ dysfunction, with a significant association between albumin, ferritin and transferrin. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  9. Challenges, responses and partnership for achieving sustainable tourism and heritage preservation

    Directory of Open Access Journals (Sweden)

    Maksin Marija

    2010-01-01

    Full Text Available The process of globalization has created the situation where the expectations of tourists are the same both with respect to the quality of services in all destinations and with respect to the authencity based on local attractions and experiences, which should be unique and different for each destination. The key element in maintaining destination attractiveness is the protection and presentation of natural and cultural heritage and its sustainable utilization for tourism development. The sustainability concept is of equal importance for long-term tourism development, destination competitiveness and heritage protection. The paper deals with the main challenges to achieving sustainable tourism and points to some key responses to them. Participation, cooperation and partnership should be a vital prerequisite for the implementation and performance of sustainable tourism and heritage protection. This attitude has been tested on several examples of good practice in heritage protection and the sustainable development of tourism destinations in Serbia. .

  10. Longitudinal Profiles of Metabolism and Bioenergetics Associated with Innate Immune Hormonal Inflammatory Responses and Amino-Acid Kinetics in Severe Sepsis and Systemic Inflammatory Response Syndrome in Children.

    Science.gov (United States)

    Spanaki, Anna Maria; Tavladaki, Theonymfi; Dimitriou, Helen; Kozlov, Andrey V; Duvigneau, J Catharina; Meleti, Eftychia; Weidinger, Adelheid; Papakonstantinou, Evangelos; Briassoulis, George

    2018-01-16

    Experimental data indicate that sepsis influences the mitochondrial function and metabolism. We aim to investigate longitudinal bioenergetic, metabolic, hormonal, amino-acid, and innate immunity changes in children with sepsis. Sixty-eight children (sepsis, 18; systemic inflammatory response syndrome [SIRS], 23; healthy controls, 27) were enrolled. Plasma amino acids were determined by high-performance liquid chromatography (HPLC); flow-cytometry expressed as mean fluorescence intensity (MFI) of heat shock protein (HSP) levels from monocytes (m) and neutrophils (n); resistin, adiponectin, and extracellular (e) HSPs evaluated by ELISA; ATP levels in white blood cells by luciferase luminescent assay; lipid peroxidation products (TBARS) by colorimetric test; nitrite and nitrate levels by chemiluminescent assay; biliverdin reductase (BVR) activity by enzymatic assay; and energy-expenditure (EE) by E-COVX. Resistin, eHSP72, eHSP90α, and nitrate were longitudinally higher in sepsis compared with SIRS (pmetabolic pattern were repressed in sepsis compared with SIRS (pmetabolism, mHSP72, and induced resistin and adiponectin (pmetabolic-hormones and eHSP72/HSP90α, repression of bioenergetics and innate immunity, hypo-metabolism, and amino-acid kinetics changes discriminate sepsis from SIRS; malnutrition, hypo-metabolism, and persistently increased resistin and adiponectin are associated with poor outcome. © 2018 American Society for Parenteral and Enteral Nutrition.

  11. Interleukin 37 expression in mice alters sleep responses to inflammatory agents and influenza virus infection

    Directory of Open Access Journals (Sweden)

    Christopher J. Davis

    2017-06-01

    Full Text Available Multiple interactions between the immune system and sleep are known, including the effects of microbial challenge on sleep or the effects of sleep loss on facets of the immune response. Cytokines regulate, in part, sleep and immune responses. Here we examine the role of an anti-inflammatory cytokine, interleukin-37 (IL-37 on sleep in a mouse strain that expresses human IL-37b (IL37tg mice. Constitutive expression of the IL-37 gene in the brains of these mice under resting conditions is low; however, upon an inflammatory stimulus, expression increases dramatically. We measured sleep in three conditions; (a under baseline conditions and after 6 h of sleep loss, (b after bolus intraperitoneal administration of lipopolysaccharide (LPS or IL-1β and (c after intranasal influenza virus challenge. Under baseline conditions, the IL37tg mice had 7% more spontaneous non-rapid eye movement sleep (NREMS during the light period than wild-type (WT mice. After sleep deprivation both WT mice and IL37tg mice slept an extra 21% and 12%, respectively, during the first 6 h of recovery. NREMS responses after sleep deprivation did not significantly differ between WT mice and IL37tg mice. However, in response to either IL-1β or LPS, the increases in time spent in NREMS were about four-fold greater in the WT mice than in the IL37tg mice. In contrast, in response to a low dose of mouse-adapted H1N1 influenza virus, sleep responses developed slowly over the 6 day recording period. By day 6, NREMS increased by 10% and REMS increased by 18% in the IL37tg mice compared to the WT mice. Further, by day 4 IL37tg mice lost less weight, remained more active, and retained their body temperatures closer to baseline values than WT mice. We conclude that conditions that promote IL-37 expression attenuate morbidity to severe inflammatory challenge.

  12. Effect of castration technique on beef calf performance, feed efficiency, and inflammatory response.

    Science.gov (United States)

    Warnock, T M; Thrift, T A; Irsik, M; Hersom, M J; Yelich, J V; Maddock, T D; Lamb, G C; Arthington, J D

    2012-07-01

    The objective of this experiment was to examine the effect of castration technique on daily feed intake (DFI), daily water intake (DWI), growth performance, residual feed intake (RFI), and inflammatory response in weaned beef calves. Seventy-five beef calves (214 ± 3.2 kg; 200 ± 26 d of age) were housed in a GrowSafe 4000 feed intake facility 7 d post weaning (15 calves/pen). Calves were offered a total mixed ration (TDN = 67.3% and CP = 12.2%, DM = 89%) for ad libitum consumption. On d 0, calves were assigned to 1 of 5 treatments (n = 15 calves/treatment): 1) steers castrated surgically pre-weaning (52 d of age; CON); 2) intact bulls (BULL); 3) bulls castrated by the Callicrate Bander on d 0 (No-Bull Enterprises LLC.; BAN); 4) bulls castrated by the Henderson Castrating Tool on d 0 (Stone Mfg & Supply Co.; HEN); and 5) bulls castrated surgically utilizing an emasculator on d 0 (SUR). Average daily gain, DFI, and DWI were recorded over 84 d. Blood was collected from a sub-sample of calves (n = 45) on d 0, 2, 6, 9, 12, and 15 relative to castration. Castration decreased (P = 0.06) ADG for castrates compared with CON from d 0 to 14 but not d 0 to 84. Daily feed intake and DWI were similar (P > 0.10) among treatments during d 0 to 84. Gain:feed was not affected by castration technique; however, RFI tended (P = 0.09) to be negative for CON and BULL compared with castrates on d 0 to 14 but not d 0 to 84. Acute phase protein analyses indicated that surgical castration (SUR or HEN) elicited a short-term inflammatory response in calves, whereas calves castrated with BAN elicited a delayed response. Calves castrated pre-weaning had improved d 0 to 14 ADG, feed intake, and inflammation response compared with calves castrated at weaning. Banding elicited a delayed negative response in ADG, DWI, and inflammation. In weaned calves, castration method did not affect performance, DFI, DWI, or inflammatory response during the 84-d trial.

  13. Initiation of an inflammatory response in resident intestinal lamina propria cells -use of a human organ culture model.

    Directory of Open Access Journals (Sweden)

    Jutta Schröder-Braunstein

    Full Text Available Resident human lamina propria immune cells serve as powerful effectors in host defense. Molecular events associated with the initiation of an intestinal inflammatory response in these cells are largely unknown. Here, we aimed to characterize phenotypic and functional changes induced in these cells at the onset of intestinal inflammation using a human intestinal organ culture model. In this model, healthy human colonic mucosa was depleted of epithelial cells by EDTA treatment. Following loss of the epithelial layer, expression of the inflammatory mediators IL1B, IL6, IL8, IL23A, TNFA, CXCL2, and the surface receptors CD14, TLR2, CD86, CD54 was rapidly induced in resident lamina propria cells in situ as determined by qRT-PCR and immunohistology. Gene microarray analysis of lamina propria cells obtained by laser-capture microdissection provided an overview of global changes in gene expression occurring during the initiation of an intestinal inflammatory response in these cells. Bioinformatic analysis gave insight into signalling pathways mediating this inflammatory response. Furthermore, comparison with published microarray datasets of inflamed mucosa in vivo (ulcerative colitis revealed a significant overlap of differentially regulated genes underlining the in vivo relevance of the organ culture model. Furthermore, genes never been previously associated with intestinal inflammation were identified using this model. The organ culture model characterized may be useful to study molecular mechanisms underlying the initiation of an intestinal inflammatory response in normal mucosa as well as potential alterations of this response in inflammatory bowel disease.

  14. Inflammatory response of disc cells against Propionibacterium acnes depends on the presence of lumbar Modic changes.

    Science.gov (United States)

    Dudli, Stefan; Miller, S; Demir-Deviren, S; Lotz, J C

    2017-09-07

    Intervertebral disc with Propionibacterium acnes (P. acnes) is suggested to be an etiology of Modic type I changes in the adjacent bone marrow. However it is unknown if disc cells can respond to P. acnes and if bone marrow cells respond to bacterial and disc metabolites draining from infected discs. Human disc cells (n = 10) were co-cultured with 10- and 100-fold excess of P. acnes over disc cells for 3 h and 24 h. Lipopolysaccharide was used as positive control. Expression of IL1, IL6, IL8, and CCL2 by disc cells was quantified by quantitative PCR. Lipase activity was measured in culture supernatants (n = 6). Human vertebral bone marrow mononuclear cells (BMNCs) (n = 2) were cultured in conditioned media from disc cell/P. acnes co-cultures and expression of IL1, IL6, IL8, and CCL2 was measured after 24 h. All disc cells responded to lipopolysaccharide but only 6/10 responded to P. acnes with increased cytokine expression. Cytokine increase was time- but not P. acnes concentration-dependent. Disc cell responsiveness was associated with the presence of lumbar Modic changes in the donor. Lipase activity was increased independent of disc cell responsiveness. BMNCs responded with inflammatory activity only when cultured in supernatants from responsive disc cell lines. Disc cell responsiveness to P. acnes associates with the presence of lumbar Modic changes. Furthermore, bone marrow cells had an inflammatory response to the cocktail of disc cytokines and P. acnes metabolites. These data indicate that low virulent P. acnes infection of the disc is a potential exacerbating factor to Modic changes.

  15. Environmentally Responsible Trade and Its Importance for Sustainable Forestry

    Directory of Open Access Journals (Sweden)

    Olena Maxymets

    2006-06-01

    Full Text Available This article focuses on the environmental component of trade, primarily foreign trade, which concerns the interests of many countries. It examines the reciprocal influence of foreign trade and the environment. The author defines environmentally responsible trade and formulates its main principles. She examines the development of trade in forest products globally and in Ukraine and evaluates the impact of different trade restrictions on the condition of forests and the forestry industry. Indicators of the efficiency of foreign trade from the economic and environmental perspectives are proposed. Underlining the need for enterprises to switch over to environmentally responsible trade, the author proposes instruments to achieve this end.

  16. Upregulation of phagocyte-derived catecholamines augments the acute inflammatory response.

    Directory of Open Access Journals (Sweden)

    Michael A Flierl

    Full Text Available Following our recent report that phagocytic cells (neutrophils, PMNs, and macrophages are newly discovered sources of catecholamines, we now show that both epinephrine and norepinephrine directly activate NFkappaB in macrophages, causing enhanced release of proinflammatory cytokines (TNFalpha, IL-1beta, IL-6. Both adrenal-intact (AD+ and adrenalectomized (ADX rodents were used, because ADX animals had greatly enhanced catecholamine release from phagocytes, facilitating our efforts to understand the role of catecholamines released from phagocytes. Phagocytes isolated from adrenalectomized rats displayed enhanced expression of tyrosine-hydroxylase and dopamine-beta-hydroxylase, two key enzymes for catecholamine production and exhibited higher baseline secretion of norepinephrine and epinephrine. The effects of upregulation of phagocyte-derived catecholamines were investigated in two models of acute lung injury (ALI. Increased levels of phagocyte-derived catecholamines were associated with intensification of the acute inflammatory response, as assessed by increased plasma leak of albumin, enhanced myeloperoxidase content in lungs, augmented levels of proinflammatory mediators in bronchoalveolar lavage fluids, and elevated expression of pulmonary ICAM-1 and VCAM-1. In adrenalectomized rats, development of ALI was enhanced and related to alpha(2-adrenoceptors engagement but not to involvement of mineralocorticoid or glucocorticoid receptors. Collectively, these data demonstrate that catecholamines are potent inflammatory activators of macrophages, upregulating NFkappaB and further downstream cytokine production of these cells. In adrenalectomized animals, which have been used to further assess the role of catecholamines, there appears to be a compensatory increase in catecholamine generating enzymes and catecholamines in macrophages, resulting in amplification of the acute inflammatory response via engagement of alpha(2-adrenoceptors.

  17. Inflammatory and metabolic responses to high-fat meals with and without dairy products in men.

    Science.gov (United States)

    Schmid, Alexandra; Petry, Nicolai; Walther, Barbara; Bütikofer, Ueli; Luginbühl, Werner; Gille, Doreen; Chollet, Magali; McTernan, Philip G; Gijs, Martin A M; Vionnet, Nathalie; Pralong, François P; Laederach, Kurt; Vergères, Guy

    2015-06-28

    Postprandial inflammation is an important factor for human health since chronic low-grade inflammation is associated with chronic diseases. Dairy products have a weak but significant anti-inflammatory effect on postprandial inflammation. The objective of the present study was to compare the effect of a high-fat dairy meal (HFD meal), a high-fat non-dairy meal supplemented with milk (HFM meal) and a high-fat non-dairy control meal (HFC meal) on postprandial inflammatory and metabolic responses in healthy men. A cross-over study was conducted in nineteen male subjects. Blood samples were collected before and 1, 2, 4 and 6 h after consumption of the test meals. Plasma concentrations of insulin, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and C-reactive protein (CRP) were measured at each time point. IL-6, TNF-α and endotoxin concentrations were assessed at baseline and endpoint (6 h). Time-dependent curves of these metabolic parameters were plotted, and the net incremental AUC were found to be significantly higher for TAG and lower for CRP after consumption of the HFM meal compared with the HFD meal; however, the HFM and HFD meals were not different from the HFC meal. Alterations in IL-6, TNF-α and endotoxin concentrations were not significantly different between the test meals. The results suggest that full-fat milk and dairy products (cheese and butter) have no significant impact on the inflammatory response to a high-fat meal.

  18. Acute inflammatory responses of nanoparticles in an intra-tracheal instillation rat model.

    Directory of Open Access Journals (Sweden)

    Andrea L Armstead

    Full Text Available Exposure to hard metal tungsten carbide cobalt (WC-Co "dusts" in enclosed industrial environments is known to contribute to the development of hard metal lung disease and an increased risk for lung cancer. Currently, the influence of local and systemic inflammation on disease progression following WC-Co exposure remains unclear. To better understand the relationship between WC-Co nanoparticle (NP exposure and its resultant effects, the acute local pulmonary and systemic inflammatory responses caused by WC-Co NPs were explored using an intra-tracheal instillation (IT model and compared to those of CeO2 (another occupational hazard NP exposure. Sprague-Dawley rats were given an IT dose (0-500 μg per rat of WC-Co or CeO2 NPs. Following 24-hr exposure, broncho-alveolar lavage fluid and whole blood were collected and analyzed. A consistent lack of acute local pulmonary inflammation was observed in terms of the broncho-alveolar lavage fluid parameters examined (i.e. LDH, albumin, and macrophage activation in animals exposed to WC-Co NP; however, significant acute pulmonary inflammation was observed in the CeO2 NP group. The lack of acute inflammation following WC-Co NP exposure contrasts with earlier in vivo reports regarding WC-Co toxicity in rats, illuminating the critical role of NP dose and exposure time and bringing into question the potential role of impurities in particle samples. Further, we demonstrated that WC-Co NP exposure does not induce acute systemic effects since no significant increase in circulating inflammatory cytokines were observed. Taken together, the results of this in vivo study illustrate the distinct differences in acute local pulmonary and systemic inflammatory responses to NPs composed of WC-Co and CeO2; therefore, it is important that the outcomes of pulmonary exposure to one type of NPs may not be implicitly extrapolated to other types of NPs.

  19. Systemic Pregabalin Attenuates Sensorimotor Responses and Medullary Glutamate Release in Inflammatory Tooth Pain Model

    Science.gov (United States)

    Narita, Noriyuki; Kumar, Naresh; Cherkas, Pavel S.; Chiang, Chen Yu; Dostrovsky, Jonathan O.; Coderre, Terence J.; Sessle, Barry J.

    2012-01-01

    Our previous studies have demonstrated that application to the tooth pulp of the inflammatory irritant mustard oil (MO) induces medullary glutamate release and central sensitization in the rat medullary dorsal horn (MDH), as well as nociceptive sensorimotor responses in craniofacial muscles in rats. There is recent evidence that anticonvulsant drugs such as pregabalin that influence glutamatergic neurotransmission are effective in several pain states. The aim of this study was to examine whether systemic administration of pregabalin attenuated glutamate release in the medulla as well as these nociceptive effects reflected in increased electromyographic (EMG) activity induced by MO application to the tooth pulp. Male adult rats were anesthetized with isofluorane (1.0~1.2 %), and jaw and tongue muscle EMG activities were recorded by needle electrodes inserted bilaterally into masseter and anterior digastric muscles and into the genioglossus muscle, and also the medullary release of glutamate was assessed by in vivo microdialysis. Pregabalin or vehicle control (isotonic saline) was administered 30 min before the pulpal application of MO or vehicle control (mineral oil). Application of mineral oil to the maxillary first molar tooth pulp produced no change in baseline EMG activity and glutamate release. However, application of MO to the pulp significantly increased both the medullary release of glutamate and EMG activity in the jaw and tongue muscles for several minutes. In contrast, pre-medication with pregabalin, but not vehicle control, significantly and dose-dependently attenuated the medullary glutamate release and EMG activity in these muscles after MO application to the tooth pulp (ANOVA, ppregabalin may attenuate the medullary release of glutamate and associated nociceptive sensorimotor responses in this acute inflammatory pulpal pain model, and that it may prove useful for the treatment of orofacial inflammatory pain states. PMID:22609939

  20. Effect of Sustained Maternal Responsivity on Later Vocabulary Development in Children with Fragile X Syndrome

    Science.gov (United States)

    Brady, Nancy; Warren, Steven F.; Fleming, Kandace; Keller, Juliana; Sterling, Audra

    2014-01-01

    Purpose: This research explored whether sustained maternal responsivity (a parent-child interaction style characterized by warmth, nurturance, and stability as well as specific behaviors, such as contingent positive responses to child initiations) was a significant variable predicting vocabulary development of children with fragile X syndrome…

  1. FREEDOM CHOICE OF THE ROMANIAN ENTERPRISES TO CORPORATE RESPONSIBILITY & SUSTAINABILITY COMPETITIVENESS

    Directory of Open Access Journals (Sweden)

    Lucretia Mariana Constantinescu

    2013-12-01

    Full Text Available The declared aim of this paper is to be an attempt to analyze the opinions regarding the corporate sustainability and responsibility that’s providing to formulate a combination of diagnosis and prognosis, assessing the past and present conditions of corporate responsibility and the way ahead by the investors of the Romanian economy during the last economic recession crisis years.

  2. Eco-innovation, Responsible Leadership and Organizational Change for Corporate Sustainability

    Directory of Open Access Journals (Sweden)

    Dorel Mihai Paraschiv

    2012-06-01

    Full Text Available Creating a sustainable development strategy is essential for organizations that seek to reduce risks associated with tightening legislation, increased energy prices and natural resources and growing customer demands. Sustainability requires the full integration of social and environmental aspects into the vision, culture and operations of an organization, a profound process of organizational change being essential. The purpose of this paper is to present the main drivers of corporate sustainability, illustrating – after a thorough literature review – the link between the following elements: corporate sustainability – a necessity in the current global context; eco-innovation – as a way to implement sustainability in an organization; responsible leadership – as the art of building and maintaining strong and moral relationships with all stakeholders; organizational culture and organizational change – the basic elements through which organizations continuously renew their processes and products, adapting them to the new context. Furthermore, the paper provides an overview of organizations active in Romania in terms of sustainability practices, in general, and the ecological component of sustainable development, in particular, by presenting the results of an exploratory questionnaire-based research. The research reflects the importance of visionary management in adopting and implementing sustainability in the responding organizations.

  3. Critical Sustainability: Setting the Limits to Growth and Responsibility in Tourism

    Directory of Open Access Journals (Sweden)

    Jarkko Saarinen

    2013-12-01

    Full Text Available The idea of sustainable development has been discussed in tourism research for almost a quarter of a century. During that time, sustainability has become an important policy framework for tourism and regional developers guiding their planning and development thinking. Sustainability has also emerged academically as an important field of research with an emphasis on defining the limits to growth and responsibilities in tourism. However, while there are urgent needs to incorporate sustainability into tourism, there is also a growing amount of frustration among scholars on the conceptual nature of sustainability and how tourism as a private-driven economic activity relates to the ideals of sustainable development. This has created an increasing need to understand and potentially reframe the concept. The purpose of this paper is to overview the conceptual dimensions of sustainable tourism and discuss some of the main sources of frustration. Based on this, it is concluded that while a conceptual plurality seems to be unavoidable, there is a need to re-frame i.e., rescale and decentralize tourism in policy frameworks and practices aiming towards sustainability.

  4. Hind limb ischemic preconditioning induces an anti-inflammatory response by remote organs in rats

    Directory of Open Access Journals (Sweden)

    M.V.P. Souza Filho

    2009-10-01

    Full Text Available Ischemic preconditioning (IPC, a strategy used to attenuate ischemia-reperfusion injury, consists of brief ischemic periods, each followed by reperfusion, prior to a sustained ischemic insult. The purpose of the present study was to evaluate the local and systemic anti-inflammatory effects of hind limb IPC in male Wistar rat (200-250 g models of acute inflammation. IPC was induced with right hind limb ischemia for 10 min by placing an elastic rubber band tourniquet on the proximal part of the limb followed by 30 min of reperfusion. Groups (N = 6-8 were submitted to right or left paw edema (PE with carrageenan (100 µg or Dextran (200 µg, hemorrhagic cystitis with ifosfamide (200 mg/kg, ip or gastric injury (GI with indomethacin (20 mg/kg, vo. Controls received similar treatments, without IPC (Sham-IPC. PE is reported as variation of paw volume (mL, vesical edema (VE as vesical wet weight (mg, vascular permeability (VP with Evans blue extravasation (µg, GI with the gastric lesion index (GLI; total length of all erosions, mm, and neutrophil migration (NM from myeloperoxidase activity. The statistical significance (P < 0.05 was determined by ANOVA, followed by the Tukey test. Carrageenan or Dextran-induced PE and VP in either paw were reduced by IPC (42-58.7%. IPC inhibited VE (38.8% and VP (54% in ifosfamide-induced hemorrhagic cystitis. GI and NM induced by indomethacin were inhibited by IPC (GLI: 90.3%; NM: 64%. This study shows for the first time that IPC produces local and systemic anti-inflammatory effects in models of acute inflammation other than ischemia-reperfusion injury.

  5. How and When Retailers’ Sustainability Efforts Translate into Positive Consumer Responses: The Interplay Between Personal and Social Factors

    NARCIS (Netherlands)

    Hofenk, D.; Birgelen, M.J.H. van; Bloemer, J.M.M.; Semeijn, J.

    2017-01-01

    This study aims to address how (through which mechanisms) and when (under which conditions) retailers’ sustainability efforts translate into positive consumer responses. Hypotheses are developed and tested through a scenario-based experiment among 672 consumers. Retailers’ assortment sustainability

  6. Increased Inflammatory Response in Cytomegalovirus Seropositive Patients with Alzheimer’s Disease

    Science.gov (United States)

    Westman, Gabriel; Ingelsson, Martin; Korsgren, Olle; Lannfelt, Lars; Sehlin, Dag; Lidehall, Anna-Karin; Eriksson, Britt-Marie

    2014-01-01

    Alzheimer’s disease (AD) has been associated with increased local inflammation in the affected brain regions, and in some studies also with elevated levels of proinflammatory cytokines in peripheral blood. Cytomegalovirus (CMV) is known to promote a more effector-oriented phenotype in the T-cell compartment, increasing with age. The aim of this study was to investigate the inflammatory response of peripheral blood mononuclear cells (PBMCs) from AD patients and non-demented (ND) controls. Using a multiplex Luminex xMAP assay targeting GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IP-10 and TNF-α, cytokine profiles from PBMCs were analysed after stimulation with anti-CD3/CD28 beads, CMV pp65 peptide mix or amyloid β (Aβ) protofibrils, respectively. CMV seropositive AD subjects presented with higher IFN-γ levels after anti-CD3/CD28 and CMV pp65 but not after Aβ stimulation, compared to CMV seropositive ND controls. When analysing IFN-γ response to anti-CD3/CD28 stimulation on a subgroup level, CMV seropositive AD subjects presented with higher levels compared to both CMV seronegative AD and CMV seropositive ND subjects. Taken together, our data from patients with clinically manifest AD suggest a possible role of CMV as an inflammatory promoter in AD immunology. Further studies of AD patients at earlier stages of disease, could provide better insight into the pathophysiology. PMID:24804776

  7. Chronic phencyclidine induces inflammatory responses and activates GSK3β in mice.

    Science.gov (United States)

    Zhu, Shenghua; Wang, Hongxing; Shi, Ruoyang; Zhang, Ruiguo; Wang, Junhui; Kong, Lynda; Sun, Yingxia; He, Jue; Kong, Jiming; Wang, Jun-Feng; Li, Xin-Min

    2014-12-01

    Use of phencyclidine (PCP) in rodents can mimic some aspects of schizophrenia. However, the underlying mechanism is still unclear. Growing evidence indicates that neuroinflammation plays a significant role in the pathophysiology of schizophrenia. In this study, we focused on inflammatory responses as target of PCP for inducing schizophrenia-like symptoms. 3-month-old C57BL/6J mice received daily injections of PCP (20 mg/kg, i.p.) or saline for one week. PCP-injected mice produced schizophrenia-like behaviours including impaired spatial short-term memory assessed by the Y-maze task and sensorimotor gating deficits in a prepulse inhibition task. Simultaneously, chronic PCP administration induced astrocyte and microglial activation in both the cortex and hippocampus. Additionally, the proinflammatory cytokine interleukin-1β was significantly up-regulated in PCP administrated mice. Furthermore, PCP treatment decreased ratio of the phospho-Ser9 epitope of glycogen synthase kinase-3β (GSK3β) over total GSK3β, which is indicative of increased GSK3β activity. These data demonstrate that chronic PCP in mouse produces inflammatory responses and GSK3β activation.

  8. Cherubism allele heterozygosity amplifies microbe-induced inflammatory responses in murine macrophages.

    Science.gov (United States)

    Prod'Homme, Virginie; Boyer, Laurent; Dubois, Nicholas; Mallavialle, Aude; Munro, Patrick; Mouska, Xavier; Coste, Isabelle; Rottapel, Robert; Tartare-Deckert, Sophie; Deckert, Marcel

    2015-04-01

    Cherubism is a rare autoinflammatory bone disorder that is associated with point mutations in the SH3-domain binding protein 2 (SH3BP2) gene, which encodes the adapter protein 3BP2. Individuals with cherubism present with symmetrical fibro-osseous lesions of the jaw, which are attributed to exacerbated osteoclast activation and defective osteoblast differentiation. Although it is a dominant trait in humans, cherubism appears to be recessively transmitted in mice, suggesting the existence of additional factors in the pathogenesis of cherubism. Here, we report that macrophages from 3BP2-deficient mice exhibited dramatically reduced inflammatory responses to microbial challenge and reduced phagocytosis. 3BP2 was necessary for LPS-induced activation of signaling pathways involved in macrophage function, including SRC, VAV1, p38MAPK, IKKα/β, RAC, and actin polymerization pathways. Conversely, we demonstrated that the presence of a single Sh3bp2 cherubic allele and pathogen-associated molecular pattern (PAMP) stimulation had a strong cooperative effect on macrophage activation and inflammatory responses in mice. Together, the results from our study in murine genetic models support the notion that infection may represent a driver event in the etiology of cherubism in humans and suggest limiting inflammation in affected individuals may reduce manifestation of cherubic lesions.

  9. In Vitro Effect of Porphyromonas gingivalis Methionine Gamma Lyase on Biofilm Composition and Oral Inflammatory Response.

    Science.gov (United States)

    Stephen, Abish S; Millhouse, Emma; Sherry, Leighann; Aduse-Opoku, Joseph; Culshaw, Shauna; Ramage, Gordon; Bradshaw, David J; Burnett, Gary R; Allaker, Robert P

    2016-01-01

    Methanethiol (methyl mercaptan) is an important contributor to oral malodour and periodontal tissue destruction. Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum are key oral microbial species that produce methanethiol via methionine gamma lyase (mgl) activity. The aim of this study was to compare an mgl knockout strain of P. gingivalis with its wild type using a 10-species biofilm co-culture model with oral keratinocytes and its effect on biofilm composition and inflammatory cytokine production. A P. gingivalis mgl knockout strain was constructed using insertion mutagenesis from wild type W50 with gas chromatographic head space analysis confirming lack of methanethiol production. 10-species biofilms consisting of Streptococcus mitis, Streptococcus oralis, Streptococcus intermedius, Fusobacterium nucleatum ssp polymorphum, Fusobacterium nucleatum ssp vincentii, Veillonella dispar, Actinomyces naeslundii, Prevotella intermedia and Aggregatibacter actinomycetemcomitans with either the wild type or mutant P. gingivalis were grown on Thermanox cover slips and used to stimulate oral keratinocytes (OKF6-TERT2), under anaerobic conditions for 4 and 24 hours. Biofilms were analysed by quantitative PCR with SYBR Green for changes in microbial ecology. Keratinocyte culture supernatants were analysed using a multiplex bead immunoassay for cytokines. Significant population differences were observed between mutant and wild type biofilms; V. dispar proportions increased (pgingivalis has been shown to affect microbial ecology in vitro, giving rise to a markedly different biofilm composition, with a more pro-inflammatory cytokine response from the keratinocytes observed. A possible role for methanethiol in biofilm formation and cytokine response with subsequent effects on oral malodor and periodontitis is suggested.

  10. Effect of different vehicles in carrageenan suspension on the rate of the inflammatory response of chicks

    Directory of Open Access Journals (Sweden)

    Alda Maria Backx Noronha Madeira

    1995-12-01

    Full Text Available This paper describes the pattern of edema, increased vascular permeability and cellular exudation elicited by the injection of different carrageenan suspensions into the foot pad of 80 male chicks, three to four-week old. Carrageenan suspensions at 0.5% were prepared in: Ringer Locke solution (RL, glucose aqueous solution 0.1% (G, demineralized water (W or phosphate buffered saline (PBS. The foot pad volume and vascular permeability were evaluated by pletismography and by Evans blue extravasation, respectively, before and at 0:15, 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 hours after injury. Cellular exudation was observed in thin sections of stained tissue 0:30, 1:30, 2:30 and 4:00 hours after injection of the carrageenan or vehicle only. The inflammatory response varied according to the carrageenan suspension used. Suspension C/PBS induced a less intense inflammatory response in foot pads of chicks than C/W, C/G and C/RL suspensions.

  11. The Systemic Inflammatory Response Syndrome (SIRS in acutely hospitalised medical patients: a cohort study

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    Storgaard Merete

    2009-12-01

    Full Text Available Abstract Background Sepsis is an infection which has evoked a systemic inflammatory response. Clinically, the Systemic Inflammatory Response Syndrome (SIRS is identified by two or more symptoms including fever or hypothermia, tachycardia, tachypnoea and change in blood leucocyte count. The relationship between SIRS symptoms and morbidity and mortality in medical emergency ward patients is unknown. Methods We conducted a prospective cohort study of the frequency of SIRS and its relationship to sepsis and death among acutely hospitalised medical patients. In 437 consecutive patients, SIRS status, blood pressure, infection and comorbidity on admission was registered together with 28-day mortality. Results A hundred and fifty-four patients (35% had SIRS on admission, 211 patients (48% had no SIRS, and 72 patients (16% had insufficient data to evaluate their SIRS status. SIRS patients were 2.2 times more frequently infected, with 66/154 SIRS patients versus 41/211 non-SIRS patients: p Conclusion We found SIRS status on admission to be moderately associated with infection and strongly related to 28-day mortality.

  12. Traumatic Reticuloperitonitis in Water Buffalo (Bubalus bubalis: Clinical Findings and the Associated Inflammatory Response

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    Maged El-Ashker

    2013-01-01

    Full Text Available The present study was carried out to describe the clinical picture of traumatic reticuloperitonitis (TRP in water buffalo (Bubalus bubalis and to evaluate the inflammatory and immunologic responses for this clinical condition. Twenty-two buffalo with acute local TRP were monitored in our study. Additionally, 10 clinically healthy buffalo were randomly selected and served as controls. Acute local TRP was initially diagnosed by clinical examination and confirmed by ultrasonographic (USG examination and/or necropsy findings. Blood samples were collected from all examined buffalo to measure the respective levels of tumor necrosis factor alpha (TNF-α, interleukin (IL-1β, IL-6, IL-10 and interferon gamma (INF-γ, serum amyloid A (SAA, C-reactive protein (CRP, haptoglobin (Hp, fibrinogen (Fb, and serum sialic acid (SSA. It was found that TNF-α, IL-1β, IL-6, IL-10, SAA, CRP, Hp, Fb, and SSA were significantly higher in buffalo with TRP than the controls. Our findings suggest that the examined immunologic variables were helpful in documenting the inflammatory response in buffalo with TRP. However, their diagnostic usefulness only becomes apparent when considered in tandem with the clinical findings for any given animal, its anamnesis, and a subsequent USG assessment. Due to the frequent complications of TRP, more accurate indicators of its occurrence and severity would be useful.

  13. Inflammatory response assessment of a hybrid tissue-engineered heart valve leaflet.

    Science.gov (United States)

    Alavi, S Hamed; Liu, Wendy F; Kheradvar, Arash

    2013-02-01

    Despite substantial research in the past few decades, only slight progress has been made toward developing biocompatible, tissue-engineered scaffolds for heart valve leaflets that can withstand the dynamic pressure inside the heart. Recent progress on the development of hybrid scaffolds, which are composed of a thin metal mesh enclosed by multi-layered tissue, appear to be promising for heart valve engineering. This approach retains all the advantages of biological scaffolds while developing a strong extracellular matrix backbone to withstand dynamic loading. This study aims to test the inflammatory response of hybrid tissue-engineered leaflets based on characterizing the activation of macrophage cells cultured on the surfaces of the tissue construct. The results indicate that integration of biological layers around a metal mesh core-regardless of its type-may reduce the evoked inflammatory responses by THP-1 monocyte-like cells. This observation implies that masking a metal implant within a tissue construct prior to implantation can hide it from the immune system and may improve the implant's biocompatibility.

  14. Inflammatory Monocytes Facilitate Adaptive CD4 T Cell Responses during Respiratory Fungal Infection

    Science.gov (United States)

    Hohl, Tobias M.; Rivera, Amariliz; Lipuma, Lauren; Gallegos, Alena; Shi, Chao; Mack, Mathias; Pamer, Eric G.

    2009-01-01

    SUMMARY Aspergillus fumigatus, a ubiquitous fungus, causes invasive disease in immunocompromised humans. Although monocytes and antigen-specific CD4 T cells contribute to defense against inhaled fungal spores, how these cells interact during infection remains undefined. Investigating the role of inflammatory monocytes and monocyte-derived dendritic cells during fungal infection, we find that A. fumigatus infection induces an influx of chemokine receptor CCR2- and Ly6C-expressing inflammatory monocytes into lungs and draining lymph nodes. Depletion of CCR2+ cells reduced A. fumigatus conidial transport from lungs to draining lymph nodes, abolished CD4 T cell priming following respiratory challenge, and impaired pulmonary fungal clearance. In contrast, depletion of CCR2+Ly6Chi monocytes during systemic fungal infection did not prevent CD4 T cell priming in the spleen. Our findings demonstrate that pulmonary CD4 T cell responses to inhaled spores require CCR2+Ly6Chi monocytes and their derivatives, revealing a compartmentally restricted function for these cells in adaptive respiratory immune responses. PMID:19917501

  15. Case Study of Hepatic Radiofrequency Ablation Causing a Systemic Inflammatory Response Under Total Intravenous Anesthesia

    Energy Technology Data Exchange (ETDEWEB)

    Schalte, Gereon; Waning, Christian; Rossaint, Rolf; Mahnken, Andreas H. [University Hospital, RWTH Aachen, Aachen, (Germany); Henzler, Dietrich [Dalhousie University, Queen Elisabeth II Health Sciences Center, Halifax (Canada); Tacke, Josef [Interventional Radiology, Klinikum Passau, Passau (Germany)

    2010-12-15

    To investigate the effects of hepatic radiofrequency ablation (RFA) in patients with malignant liver disease with respect to inflammation activation and stress response. In an observational trial, we investigated the physiologic parameters of 17 patients (20 interventions) who underwent percutaneous RFA under general anesthesia after applying total intravenous anesthesia. TNF{alpha}, IL-6, IL-8, IL-10, adrenaline and noradrenaline, liver enzymes, lactate and creatine kinase were determined pre-interventionally after induction of anesthesia (T1), 90 minutes after initiation of RFA (T2), immediately after the conclusion of the procedure (T3), and 24 hours after the procedure (T4). A significant increase in body temperature (p < 0.001), and mean arterial pressure (p = 0.001) were measured intraoperatively (T2) and the day after the procedure (T4). Increased levels of IL-6 were measured at T3 and T4 (p = 0.001). IL-10 increased immediately after the procedure (T3; p = 0.007). IL-6 levels correlated well with the total energy applied ({gamma} = 0.837). Significant increases in the levels of adrenaline and noradrenaline were present at T3 and T4 (p < 0.001). The RFA-induced destruction of hepatic tissue was associated with increased levels of AST, ALT, GLDH and LDH. Percutaneous RFA of hepatic malignancies causes an inflammatory and endocrine activation, similar to the systemic inflammatory response syndrome. These effects have to be taken in account when dealing with patients susceptible to sepsis or multi-organ failure

  16. Pathogenesis and inflammatory response to Edwardsiella tarda infection in the zebrafish.

    Science.gov (United States)

    Pressley, Meagan E; Phelan, Peter E; Witten, P Eckhard; Mellon, Mark T; Kim, Carol H

    2005-01-01

    The zebrafish (Danio rerio) is a widely used model for developmental biology, neurobiology, toxicology, and genetic disease. Recently, the zebrafish has been recognized as a valuable model for infectious disease and immunity. In this study the pathogenesis and inflammatory cytokine response of zebrafish to experimental Edwardsiella tarda infection was characterized. In challenge experiments, zebrafish embryos were susceptible to infection by immersion. Adult fish were susceptible to challenge by intraperitoneal (ip) injection but not static immersion unless the epithelial layer was perturbed by scraping prior to exposure. To determine if E. tarda infection induces a typical acute inflammatory response, mRNA expression levels of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNFalpha) were assessed by quantitative real-time PCR. The expression levels of IL-1beta and TNFalpha were significantly upregulated in infected zebrafish embryos and adults. The methods developed in this study will be particularly valuable for targeted gene disruption studies of host immune components and in zebrafish genetic screens.

  17. Comprehensive DNA Adduct Analysis Reveals Pulmonary Inflammatory Response Contributes to Genotoxic Action of Magnetite Nanoparticles

    Directory of Open Access Journals (Sweden)

    Kousuke Ishino

    2015-02-01

    Full Text Available Nanosized-magnetite (MGT is widely utilized in medicinal and industrial fields; however, its toxicological properties are not well documented. In our previous report, MGT showed genotoxicity in both in vitro and in vivo assay systems, and it was suggested that inflammatory responses exist behind the genotoxicity. To further clarify mechanisms underlying the genotoxicity, a comprehensive DNA adduct (DNA adductome analysis was conducted using DNA samples derived from the lungs of mice exposed to MGT. In total, 30 and 42 types of DNA adducts were detected in the vehicle control and MGT-treated groups, respectively. Principal component analysis (PCA against a subset of DNA adducts was applied and several adducts, which are deduced to be formed by inflammation or oxidative stress, as the case of etheno-deoxycytidine (εdC, revealed higher contributions to MGT exposure. By quantitative-LC-MS/MS analysis, εdC levels were significantly higher in MGT-treated mice than those of the vehicle control. Taken together with our previous data, it is suggested that inflammatory responses might be involved in the genotoxicity induced by MGT in the lungs of mice.

  18. LYATK1 potently inhibits LPS-mediated pro-inflammatory response

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Feng [Department of Intensive Care Unit, Taixing People" ' s Hospital, Taixing, Jiangsu Province, 225400 (China); Liu, Yuan [Department of Ophthalmology, Nanjing First Hospital, Nanjing Medical University, Nanjing (China); Wang, Xiujuan; Kong, Wei [Department of Intensive Care Unit, Taixing People" ' s Hospital, Taixing, Jiangsu Province, 225400 (China); Zhao, Feng, E-mail: taixingzhaofeng163@163.com [Department of Intensive Care Unit, Taixing People" ' s Hospital, Taixing, Jiangsu Province, 225400 (China)

    2016-01-29

    Lipopolysaccharide (LPS)-primed monocytes/macrophages produce pro-inflammatory cytokines, which could lead to endotoxin shock. TGF-β-activated kinase1 (TAK1) activation is involved in the process. In the current study, we studied the potential effect of a selective TAK1 inhibitor, LYTAK1, on LPS-stimulated response both in vitro and in vivo. We demonstrated that LYTAK1 inhibited LPS-induced mRNA expression and production of several pro-inflammatory cytokines [interleukin 1β (IL-1β), tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6)] in RAW 264.7 macrophages. LYTAK1's activity was almost nullified with TAK1 shRNA-knockdown. Meanwhile, in both primary mouse bone marrow derived macrophages (BMDMs) and human peripheral blood mononuclear cells (PBMCs), LPS-induced pro-inflammatory cytokine production was again attenuated with LYTAK1 co-treatment. Molecularly, LYTAK1 dramatically inhibited LPS-induced TAK1-nuclear factor kappa B (NFκB) and mitogen-activated protein kinase (Erk, Jnk and p38) activation in RAW 264.7 cells, mouse BMDMs and human PBMCs. In vivo, oral administration of LYTAK1 inhibited LPS-induced activation of TAK1-NFκB-p38 in ex-vivo cultured PBMCs, and cytokine production and endotoxin shock in mice. Together, these results demonstrate that LYTAK1 inhibits LPS-induced production of several pro-inflammatory cytokines and endotoxin shock probably through blocking TAK1-regulated signalings. - Highlights: • LYTAK1 inhibits LPS-induced pro-inflammatory cytokine production in RAW 264.7 cells. • The effect by LYTAK1 is more potent than other known TAK1 inhibitors. • LYTAK1 inhibits LPS-induced cytokine production in primary macrophages/monocytes. • LYTAK1 inhibits LPS-induced TAK1-NFκB and MAPK activation in macrophages/monocytes. • LYTAK1 gavage inhibits LPS-induced endotoxin shock and cytokine production in mice.

  19. Interrelationship between the early inflammatory response and subsequent fibrosis after radiation exposure. [X radiation, rats

    Energy Technology Data Exchange (ETDEWEB)

    Ullrich, R.L.; Casarett, G.W.

    1977-10-01

    The mechanistic relationships between the early inflammatory response and subsequent fibrosis seen after radiation exposure were studied in rats given X-ray doses of either 2000 or 5000 rad to standardized fields of the inner thigh. The animals were further subdivided into those receiving no additional treatment and those depleted of complement with cobra-venom factor. The results are consistent with the hypothesis that two mechanisms are responsible for the increases in extravasation rate and vascular injury seen after irradiation. First, direct cytocidal damage; second, chemically mediated, possibly complement-dependent, mechanisms. In addition, these data suggest that both direct and indirect damage to the vasculature play a role in influencing the subsequent late-radiation-induced fibrosis.

  20. Antibodies against a surface protein of Streptococcus pyogenes promote a pathological inflammatory response.

    Directory of Open Access Journals (Sweden)

    Fredrik Kahn

    Full Text Available Streptococcal toxic shock syndrome (STSS caused by Streptococcus pyogenes is a clinical condition with a high mortality rate despite modern intensive care. A key feature of STSS is excessive plasma leakage leading to hypovolemic hypotension, disturbed microcirculation and multiorgan failure. Previous work has identified a virulence mechanism in STSS where M1 protein of S. pyogenes forms complexes with fibrinogen that activate neutrophils to release heparin-binding protein (HBP, an inducer of vascular leakage. Here, we report a marked inter-individual difference in the response to M1 protein-induced HBP release, a difference found to be related to IgG antibodies directed against the central region of the M1 protein. To elicit massive HBP release, such antibodies need to be part of the M1 protein-fibrinogen complexes. The data add a novel aspect to bacterial pathogenesis where antibodies contribute to the severity of disease by promoting a pathologic inflammatory response.

  1. Immune and Inflammatory Responses in the Central Nervous System: Modulation by Astrocytes

    DEFF Research Database (Denmark)

    Penkowa, Milena; hidalgo, juan; aschner, michael

    2008-01-01

    Beyond their long-recognized support functions, astrocytes are active partners of neurons in processing information, synaptic integration, and production of trophic factors, just to name a few. Both microglia and astrocytes produce and secrete a number of cytokines, modulating and integrating...... the communication between hematogenous cells and resident cells of the central nervous system (CNS). This review will address (1) the functions of astrocytes in the normal brain and (2) their role in surveying noxious stimuli within the brain, with particular emphasis on astrocytic responses to damage or disease......, a process referred to as reactive astrogliosis/ astrocytosis. In addition, the review will discuss (3) the role of astrocytes as an abundant cellular source for immunoregulatory (cytokines) factors, and their fundamental roles in the type and extent of CNS immune and inflammatory responses. (4) Recent...

  2. The relationship between the inflammatory response and cell adhesion on alginate-chitosan-alginate microcapsules after transplantation.

    Science.gov (United States)

    Li, Shen; Zhang, Ying; Chen, Li; Li, Na; Xie, Hongguo; Guo, Xin; Zhao, Shan; Yu, Weiting; Lv, Yan; Lv, Guojun; Wu, Huijian; Ma, Xiaojun

    2015-07-01

    Cell microencapsulation technology is a potential alternative therapy, but cell overgrowth and adhesion on the microcapsules after transplantation shortens their time of therapeutic efficacy. Inflammatory cells were the main cells that adhered to the microcapsules, so understanding the body's inflammatory processes would help to better identify the mechanisms of cell adhesion to the outer surface of the microcapsules. Our study measured the inflammatory cells and the cytokines and characterized the associated changes in the alginate-chitosan-alginate (ACA) microcapsules 1, 7, 14, and 28 days after implantation in the peritoneal cavity. Then the relationship between the inflammatory response and cell adhesion on the microcapsules was evaluated by multiple regression analysis. The results showed that the microcapsules did not evoke a systemic inflammatory response, but initiated a local inflammatory response in the peritoneal cavity. Furthermore, the correlation analysis showed that the level of cell adhesion on the microcapsules was related to the number of lymphocytes and macrophages, and the amount of IL-6, IL-10, and MCP-1 in the peritoneal cavity. Our results may provide a foundation for reducing the immune response to these microcapsules, prolonging graft survival and improving the efficacy of these treatments. © 2014 Wiley Periodicals, Inc.

  3. CSF-1 receptor-dependent colon development, homeostasis and inflammatory stress response.

    Directory of Open Access Journals (Sweden)

    Duy Huynh

    Full Text Available The colony stimulating factor-1 (CSF-1 receptor (CSF-1R directly regulates the development of Paneth cells (PC and influences proliferation and cell fate in the small intestine (SI. In the present study, we have examined the role of CSF-1 and the CSF-1R in the large intestine, which lacks PC, in the steady state and in response to acute inflammation induced by dextran sulfate sodium (DSS. As previously shown in mouse, immunohistochemical (IHC analysis of CSF-1R expression showed that the receptor is baso-laterally expressed on epithelial cells of human colonic crypts, indicating that this expression pattern is shared between species. Colons from Csf1r null and Csf1(op/op mice were isolated and sectioned for IHC identification of enterocytes, enteroendocrine cells, goblet cells and proliferating cells. Both Csf1r(-/- and Csf1(op/op mice were found to have colon defects in enterocytes and enteroendocrine cell fate, with excessive goblet cell staining and reduced cell proliferation. In addition, the gene expression profiles of the cell cycle genes, cyclinD1, c-myc, c-fos, and c-myb were suppressed in Csf1r(-/- colonic crypt, compared with those of WT mice and the expression of the stem cell marker gene Lgr5 was markedly reduced. However, analysis of the proliferative responses of immortalized mouse colon epithelial cells (lines; Immorto-5 and YAMC indicated that CSF-1R is not a major regulator of colonocyte proliferation and that its effects on proliferation are indirect. In an examination of the acute inflammatory response, Csf1r(+/- male mice were protected from the adverse affects of DSS-induced colitis compared with WT mice, while Csf1r(+/- female mice were significantly less protected. These data indicate that CSF-1R signaling plays an important role in colon homeostasis and stem cell gene expression but that the receptor exacerbates the response to inflammatory challenge in male mice.

  4. Pronounced inflammatory response to endotoxaemia during nighttime: a randomised cross-over trial.

    Directory of Open Access Journals (Sweden)

    Mahdi Alamili

    Full Text Available BACKGROUND: Circadian variation in bodily functions has been shown to impact health in acute and chronic medical conditions. Little is known about the relationship between circadian rhythm and sepsis in humans. We aimed to investigate circadian variations in the host response in a human endotoxaemia model. DESIGN AND METHODS: A cross-over study, where 12 healthy young men received E. coli endotoxin (lipopolysaccharide, LPS 0.3 ng/kg at 12 noon and, on another day, at 12 midnight. Blood samples were analysed for pro- and anti-inflammatory cytokines: tumour-necrosis factor (TNF-alpha, soluble TNF receptors (sTNF-R-1 and -2, interleukin (IL-1beta, IL-1 receptor antagonist (IL-1Ra, IL-6, and IL-10 as well as YKL-40 and the oxidative stress markers malondialdehyde (MDA, ascorbic acid (AA and dehydroascorbic acid (DHA before and at 2, 4, 6 and 8 hours after LPS administration. RESULTS: The levels of MDA and IL-10 where significantly higher during the day time (P<0.05 whereas levels of TNF-alpha, sTNF-RI, sTNF-RII, IL-1Ra, IL-6, and YKL-40 were higher (P<0.01 for all comparisons during the night time. No significant differences were seen in the levels of AA and DHA. CONCLUSION: A day-night difference in the acute phase response to endotoxaemia exists in healthy volunteers with a more pronounced inflammatory response during the night time. This circadian difference in the response to endotoxaemia may play an important role in the clinical setting and should be investigated further.

  5. Diet-Induced Obesity Reprograms the Inflammatory Response of the Murine Lung to Inhaled Endotoxin

    Energy Technology Data Exchange (ETDEWEB)

    Tilton, Susan C.; Waters, Katrina M.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Zangar, Richard C.; Lee, Monika K.; Bigelow, Diana J.; Pounds, Joel G.; Corley, Richard A.

    2013-03-01

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures.

  6. Interleukin-7 receptor blockade suppresses adaptive and innate inflammatory responses in experimental colitis

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    Willis Cynthia R

    2012-10-01

    Full Text Available Abstract Background Interleukin-7 (IL-7 acts primarily on T cells to promote their differentiation, survival, and homeostasis. Under disease conditions, IL-7 mediates inflammation through several mechanisms and cell types. In humans, IL-7 and its receptor (IL-7R are increased in diseases characterized by inflammation such as atherosclerosis, rheumatoid arthritis, psoriasis, multiple sclerosis, and inflammatory bowel disease. In mice, overexpression of IL-7 results in chronic colitis, and T-cell adoptive transfer studies suggest that memory T cells expressing high amounts of IL-7R drive colitis and are maintained and expanded with IL-7. The studies presented here were undertaken to better understand the contribution of IL-7R in inflammatory bowel disease in which colitis was induced with a bacterial trigger rather than with adoptive transfer. Methods We examined the contribution of IL-7R on inflammation and disease development in two models of experimental colitis: Helicobacter bilis (Hb-induced colitis in immune-sufficient Mdr1a−/− mice and in T- and B-cell-deficient Rag2−/− mice. We used pharmacological blockade of IL-7R to understand the mechanisms involved in IL-7R-mediated inflammatory bowel disease by analyzing immune cell profiles, circulating and colon proteins, and colon gene expression. Results Treatment of mice with an anti-IL-7R antibody was effective in reducing colitis in Hb-infected Mdr1a−/− mice by reducing T-cell numbers as well as T-cell function. Down regulation of the innate immune response was also detected in Hb-infected Mdr1a−/− mice treated with an anti-IL-7R antibody. In Rag2−/− mice where colitis was triggered by Hb-infection, treatment with an anti-IL-7R antibody controlled innate inflammatory responses by reducing macrophage and dendritic cell numbers and their activity. Conclusions Results from our studies showed that inhibition of IL-7R successfully ameliorated inflammation and disease development

  7. Ventilation during cardiopulmonary bypass did not attenuate inflammatory response or affect postoperative outcomes.

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    Durukan, Ahmet Baris; Gurbuz, Hasan Alper; Salman, Nevriye; Unal, Ertekin Utku; Ucar, Halil Ibrahim; Yorgancioglu, C E M

    2013-07-01

    Cardiopulmonary bypass causes a series of inflammatory events that have adverse effects on the outcome. The release of cytokines, including interleukins, plays a key role in the pathophysiology of the process. Simultaneously, cessation of ventilation and pulmonary blood flow contribute to ischaemia-reperfusion injury in the lungs when reperfusion is maintained. Collapse of the lungs during cardiopulmonary bypass leads to postoperative atelectasis, which correlates with the amount of intrapulmonary shunt. Atelectasis also causes post-perfusion lung injury. In this study, we aimed to document the effects of continued low-frequency ventilation on the inflammatory response following cardiopulmonary bypass and on outcomes, particularly pulmonary function. Fifty-nine patients subjected to elective coronary bypass surgery were prospectively randomised to two groups, continuous ventilation (5 ml/kg tidal volume, 5/min frequency, zero end-expiratory pressure) and no ventilation, during cardiopulmonary bypass. Serum interleukins 6, 8 and 10 (as inflammatory markers), and serum lactate (as a marker for pulmonary injury) levels were studied, and alveolar- arterial oxygen gradient measurements were made after the induction of anaesthesia, and immediately, one and six hours after the discontinuation of cardiopulmonary bypass. There were 29 patients in the non-ventilated and 30 in the continuously ventilated groups. The pre-operative demographics and intra-operative characteristics of the patients were comparable. The serum levels of interleukin 6 (IL-6) increased with time, and levels were higher in the nonventilated group only immediately after discontinuation of cardiopulmonary bypass. IL-8 levels significantly increased only in the non-ventilated group, but the levels did not differ between the groups. Serum levels of IL-10 and lactate also increased with time, and levels of both were higher in the non-ventilated group only immediately after the discontinuation of

  8. A Missense LRRK2 Variant Is a Risk Factor for Excessive Inflammatory Responses in Leprosy.

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    Vinicius M Fava

    2016-02-01

    Full Text Available Depending on the epidemiological setting, a variable proportion of leprosy patients will suffer from excessive pro-inflammatory responses, termed type-1 reactions (T1R. The LRRK2 gene encodes a multi-functional protein that has been shown to modulate pro-inflammatory responses. Variants near the LRRK2 gene have been associated with leprosy in some but not in other studies. We hypothesized that LRRK2 was a T1R susceptibility gene and that inconsistent association results might reflect different proportions of patients with T1R in the different sample settings. Hence, we evaluated the association of LRRK2 variants with T1R susceptibility.An association scan of the LRRK2 locus was performed using 156 single-nucleotide polymorphisms (SNPs. Evidence of association was evaluated in two family-based samples: A set of T1R-affected and a second set of T1R-free families. Only SNPs significant for T1R-affected families with significant evidence of heterogeneity relative to T1R-free families were considered T1R-specific. An expression quantitative trait locus (eQTL analysis was applied to evaluate the impact of T1R-specific SNPs on LRRK2 gene transcriptional levels.A total of 18 T1R-specific variants organized in four bins were detected. The core SNP capturing the T1R association was the LRRK2 missense variant M2397T (rs3761863 that affects LRRK2 protein turnover. Additionally, a bin of nine SNPs associated with T1R were eQTLs for LRRK2 in unstimulated whole blood cells but not after exposure to Mycobacterium leprae antigen.The results support a preferential association of LRRK2 variants with T1R. LRRK2 involvement in T1R is likely due to a pathological pro-inflammatory loop modulated by LRRK2 availability. Interestingly, the M2397T variant was reported in association with Crohn's disease with the same risk allele as in T1R suggesting common inflammatory mechanism in these two distinct diseases.

  9. Sirtuin 6 suppresses hypoxia-induced inflammatory response in human osteoblasts via inhibition of reactive oxygen species production and glycolysis-A therapeutic implication in inflammatory bone resorption.

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    Hou, Kuo-Liang; Lin, Sze-Kwan; Chao, Ling-Hsiu; Hsiang-Hua Lai, Eddie; Chang, Cheng-Chi; Shun, Chia-Tung; Lu, Wan-Yu; Wang, Jyh-Horng; Hsiao, Michael; Hong, Chi-Yuan; Kok, Sang-Heng

    2017-03-01

    Elevated glycolytic activity and redox imbalance induced by tissue hypoxia are common phenomena of chronic inflammation, including inflammatory bone diseases such as arthritis. However, relation between glycolysis and redox signaling in the inflammatory milieu is unclear. The histone deacetylase sirtuin 6 (SIRT6) is a crucial modulator of inflammation and glucose metabolism, and it is also involved in cellular protection against oxidative injury. The aims of the study were to examine the connection between glycolysis and reactive oxygen species (ROS) production in human osteoblastic cells (HOB) and whether SIRT6 modulates inflammatory response via regulation of glycolytic activity and ROS generation. In HOB cultured under hypoxia, expression of lactate dehydrogenase A (LDHA), lactate production and ROS generation were examined. The reciprocal effects between lactate and ROS production and their impact on inflammatory cytokine induction were assessed. The action of SIRT6 on the above reactions was determined. In a rat model of collagen-induced arthritis (CIA), the relation between inflammatory activity and osteoblastic expression of LDHA, level of oxidative lesions, Cyr61 synthesis and macrophage recruitment were examined in joints with or without lentiviral-SIRT6 gene therapy. Results showed that hypoxia stress enhanced lactate and LDHA production in HOB. ROS generation was also increased, and there was a positive feedback between glycolysis and ROS formation. Overexpression of SIRT6 attenuated hypoxia-enhanced glycolysis and ROS generation. Hypoxia-induced expressions of Cyr61, TNF-α, IL-1β, and IL-6 were suppressed by SIRT6 and the inhibitory effects overlapped with antiglycolytic and antioxidation mechanisms. In the model of CIA, forced expression of SIRT6 ameliorated disease progression, osteoblastic synthesis of Cyr61, and macrophage recruitment. More importantly, expression of LDHA and oxidative lesions were decreased in osteoblasts of SIRT6-treated joints

  10. The response of human macrophages to β-glucans depends on the inflammatory milieu.

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    Cristina Municio

    Full Text Available BACKGROUND: β-glucans are fungal cell wall components that bind to the C-type lectin-like receptor dectin-1. Polymorphisms of dectin-1 gene are associated with susceptibility to invasive fungal infection and medically refractory ulcerative colitis. The purpose of this study has been addressing the response of human macrophages to β-glucans under different conditions mimicking the composition of the inflammatory milieu in view of the wide plasticity and large range of phenotypical changes showed by these cells, and the relevant role of dectin-1 in several pathophysiological conditions. PRINCIPAL FINDINGS: Serum-differentiated macrophages stimulated with β-glucans showed a low production of TNFα and IL-1β, a high production of IL-6 and IL-23, and a delayed induction of cyclooxygenase-2 and PGE2 biosynthesis that resembled the responses elicited by crystals and those produced when phagosomal degradation of the phagocytic cargo increases ligand access to intracellular pattern recognition receptors. Priming with a low concentration of LPS produced a rapid induction of cyclooxygenase-2 and a synergistic release of PGE2. When the differentiation of the macrophages was carried out in the presence of M-CSF, an increased expression of dectin-1 B isoform was observed. In addition, this treatment made the cells capable to release arachidonic acid in response to β-glucan. CONCLUSIONS: These results indicate that the macrophage response to fungal β-glucans is strongly influenced by cytokines and microbial-derived factors that are usual components of the inflammatory milieu. These responses can be sorted into three main patterns i an elementary response dependent on phagosomal processing of pathogen-associated molecular patterns and/or receptor-independent, direct membrane binding linked to the immunoreceptor tyrosine-based activation motif-bearing transmembrane adaptor DNAX-activating protein 12, ii a response primed by TLR4-dependent signals, and iii

  11. Turning 21: Induction of miR-21 as a key switch in the inflammatory response

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    Frederick J Sheedy

    2015-01-01

    Full Text Available miR-21 is one of the most highly expressed members of the small non-coding microRNA family in many mammalian cell types. Its expression is further enhanced in many diseased states including solid tumors, cardiac injury and inflamed tissue. Whilst the induction of miR-21 by inflammatory stimuli cells has been well documented in both hematopoietic cells of the immune system (particularly monocytes/macrophages but also dendritic and T-cells and non-hematopoietic tumorigenic cells, the exact functional outcome of this elevated miR-21 is less obvious. Recent studies have confirmed a key role for miR-21 in the resolution of inflammation and in negatively regulating the proinflammatory response induced by many of the same stimuli that trigger miR-21 induction itself. In particular, miR-21 has emerged as a key mediator of the anti-inflammatory response in macrophages. This suggests that miR-21 inhibition in leukocytes will promote inflammation and may enhance current therapies for defective immune responses such as cancer, mycobacterial vaccines or Th2-associated allergic inflammation. At the same time, miR-21 has been shown to promote inflammatory mediators in non-hematopoietic cells resulting in neoplastic transformation. This review will focus on functional studies of miR-21 during inflammation which are complicated by the numerous molecular targets and processes that have emerged as miR-21 sensitive. It may be that the exact functional outcome of miR-21 is determined by multiple features including the cell type affected, the inducing signal, the transcriptomic profile of the cell, which ultimately affect the availability and ability to engage different target mRNAs and bring about its unique responses. Reviewing this data may illustrate that RNA-based oligonucleotide therapies for different diseases based upon miR-21 may have to target the unique and operative miRNA:mRNA interactions functionally active disease.

  12. Viral mechanisms involved in the transcriptional CBP/p300 regulation of inflammatory and immune responses.

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    Revilla, Yolanda; Granja, Aitor G

    2009-01-01

    The transcriptional coactivators CREB-binding protein (capital ES, Cyrilliccapital VE, Cyrilliccapital ER, Cyrillic) and small er, Cyrillic300 regulate inducible transcription in multiple cellular processes and during the establishment of inflammatory and immune response. These closely related transcriptional coactivators arc able to modulate the transcription of specific genes, modify chromatin structure, and influence cell-cycle progression. Several viruses have been shown to interfere with CREB-binding protein/small er, Cyrillic300 function, modulating their transcriptional activity. During a viral infection, reprogramming of the host cell gene expression pattern is required to establish an adequate antiviral response and, thus, many viruses encode proteins that can influence or interfere with cellular signals to evade inflammation and immune response. The mechanism of transcriptional regulation by coactivator proteins, including small er, Cyrillic300/CBP, has been the focus of intense study. As a part of this, some of the molecular instruments developed by viruses to counteract the host response and their role in the regulation of inflammation and immune response are summarized in this review.

  13. Monocyte / macrophage inflammatory response pathways to combat Francisella infection: possible therapeutic targets?

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    Devyn D Gillette

    2014-02-01

    Full Text Available Francisella tularensis can bypass and suppress host immune responses, even to the point of manipulating immune cell phenotypes and intercellular inflammatory networks. Strengthening these responses such that immune cells more readily identify and destroy the bacteria is likely to become a viable (and perhaps necessary strategy for combating infections with Francisella, especially given the likelihood of antibiotic resistance in the foreseeable future. Monocytes and macrophages offer a niche wherein Francisella can invade and replicate, resulting in substantially higher bacterial load that can overcome the host. As such, understanding their responses to Francisella may uncover potential avenues of therapy that could promote a lowering of bacterial burden and clearance of infection. These response pathways include Toll-like Receptor 2 (TLR2, the caspase-1 inflammasome, Interferons, NADPH oxidase, Phosphatidylinositide 3-kinase (PI3K and the Ras pathway. In this review we summarize the literature pertaining to the roles of these pathways during Francisella infection, with an emphasis on monocyte / macrophage responses. The therapeutic targeting of one or more such pathways may ultimately become a valuable tool for the treatment of tularemia, and several possibilities are discussed.

  14. SOCIAL RESPONSIBILITY - A VIABLE INSTRUMENT FOR SUSTAINABLE DEVELOPMENT OF THE TOURISM INDUSTRY IN SOUTH WEST OLTENIA

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    POPA OANA

    2012-06-01

    Full Text Available The paper emphasizes the need for the tourism sector to adopt a policy of social responsibility for building sustainable development, necessary for the socio-economic recovery of Romania. The study includes a sample of 68 hotels in the five counties of South West Oltenia Region. Data for the research was collected by accessing the official websites for each hotel in order to analyze the degree of implementation of social responsibility on the basis of ten variables, required to achieve a sustainable tourism. The findings reveal a lack of transparency and involvement in social responsibility of the hotel industry in South West Oltenia. Research has shown that accomodation and tourism sector in the region analyzed is far from reaching the international standards, so the adoption of recommendations on best practices would be an important step forward for enhancing sustainable tourism in Romania.

  15. Sustainable Entrepreneurship Orientation: A Reflection on Status-Quo Research on Factors Facilitating Responsible Managerial Practices

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    Sascha Kraus

    2018-02-01

    Full Text Available With the global financial system having undergone vast changes since the financial crisis of 2007, scientific research concerning the investor’s point of view on sustainable investments has drastically increased. However, there remains a lack of research focused on the entrepreneur’s angle regarding sustainable oriented investments. The aim of this paper is to contribute to the understanding of sustainable financial markets by bringing together entrepreneurial and financial research. This paper provides a structured literature review, based on which the authors identify three relevant levels that they believe have an effect on the successful implementation of managerial sustainable practices; these are the individual, the firm, and the contextual levels. The results show that on the individual level sustainable entrepreneurs tend to derive their will to act more sustainably from their personal values or traits. On the organizational level, though, it can be concluded that an small and medium sized enterprise’s internal culture and the reconfiguration of resources are critical determinants for adopting a sustainable entrepreneurial orientation. Finally, on the contextual level, researchers have focused on a better understanding of how entrepreneurs can help society and the environment through sustainable entrepreneurship, and how they can act as role models or change agents in light of the fact that the choice of investing or financing based on sustainability is still in its infancy. By providing an overview on facilitating factors for responsible managerial practices on the entrepreneur’s side, this research contributes to a better understanding for both theory and practice on how sustainable practices can be implemented and facilitated.

  16. Sustainable Ergonomic Program - Basic Condition for Implementation of Corporate Social Responsibility

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    Marková, Petra; Beňo, Rastislav; Hatiar, Karol

    2012-12-01

    Gradually increasing pressure on companies to start to behave socially responsible is a response to social, environmental and economic requirements. The society faces a period of changes that have occurred since the beginning of the crisis and revealing weaknesses in the economy. We become witnesses of rapid changes and challenges posed by globalization, lack of resources, demographic structure and innovation. Objective necessity becomes a corporate social responsibility (CSR) already at the companies’ level, which is supported by the approach of the EU institutions and the Slovak Republic. One of the possible appliance through which we can contribute to the sustainability of CSR are sustainable ergonomic programs. When we want to talk about sustainable ergonomic program is important to focus on three key areas. The first area is the Impact of technic and technology to employees at work, the second area is the Importance and impact of socially responsible HR in ergonomics and last area is the Creation of the work environment in relation to environmental sustainability. Ergonomic programs sustainability requires to apply appropriate methods for evaluation of their cost benefit and health effect.

  17. Intermittent fasting could ameliorate cognitive function against distress by regulation of inflammatory response pathway

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    Marjan Shojaie

    2017-11-01

    Full Text Available Undesirable and desirable effects of stressors on the body are assigned to distress and eustress, respectively. Immune system and brain are the most susceptible parts to stressful conditions, whereas long-lasting alterations in putative immune proteins involved in tension such as corticosterone (CORT, interleukin 6 (IL-6, and tumor necrosis factor-alpha (TNF-α can impact learning and memory. Intermittent fasting (IF is a repeated regular cycle of dietary restriction with well-known beneficial properties on the body. The aim of this study was to identify the eustress effects of IF on cognitive function by assessing the critical inflammatory factors in chronic distress. Forty male mice were divided into four groups (n = 10/group. Distress and control normally received food and water, whereas IF and IF with distress groups were daily deprived of food and water for two hours. In the second week, the electrical foot shock was induced to distress and IF with distress groups. Finally, the cognitive functions of all mice were evaluated by Barnes maze, their blood samples were taken to determine the plasma level of CORT, IL-6 and TNF-α, and the removed brain and adrenal glands were weighed in the third week. A significant gain in plasma level of CORT, IL-6 and TNF-α with a considerable brain hypotrophy and adrenal hypertrophy was found in distress group, whereas IF caused a remarkable reduction of the plasma inflammatory factors, especially in IF with distress mice (P ≤ 0.05. In conclusion, IF could improve cognitive function and preserve the brain against distress by regulation of inflammatory response pathway.

  18. Intermittent fasting could ameliorate cognitive function against distress by regulation of inflammatory response pathway.

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    Shojaie, Marjan; Ghanbari, Farzane; Shojaie, Nasrin

    2017-11-01

    Undesirable and desirable effects of stressors on the body are assigned to distress and eustress, respectively. Immune system and brain are the most susceptible parts to stressful conditions, whereas long-lasting alterations in putative immune proteins involved in tension such as corticosterone (CORT), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) can impact learning and memory. Intermittent fasting (IF) is a repeated regular cycle of dietary restriction with well-known beneficial properties on the body. The aim of this study was to identify the eustress effects of IF on cognitive function by assessing the critical inflammatory factors in chronic distress. Forty male mice were divided into four groups (n = 10/group). Distress and control normally received food and water, whereas IF and IF with distress groups were daily deprived of food and water for two hours. In the second week, the electrical foot shock was induced to distress and IF with distress groups. Finally, the cognitive functions of all mice were evaluated by Barnes maze, their blood samples were taken to determine the plasma level of CORT, IL-6 and TNF-α, and the removed brain and adrenal glands were weighed in the third week. A significant gain in plasma level of CORT, IL-6 and TNF-α with a considerable brain hypotrophy and adrenal hypertrophy was found in distress group, whereas IF caused a remarkable reduction of the plasma inflammatory factors, especially in IF with distress mice (P ≤ 0.05). In conclusion, IF could improve cognitive function and preserve the brain against distress by regulation of inflammatory response pathway.

  19. Effect of oral mesalamine on inflammatory response in acute uncomplicated diverticulitis.

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    Nespoli, Luca; Lo Bianco, Giulia; Uggeri, Fabio; Romano, Fabrizio; Nespoli, Angelo; Bernasconi, Davide Paolo; Gianotti, Luca

    2015-07-21

    To evaluate the impact of mesalamine administration on inflammatory response in acute uncomplicated diverticulitis. We conducted a single centre retrospective cohort study on patients admitted to our surgical department between January 2012 and May 2014 with a computed tomography -confirmed diagnosis of acute uncomplicated diverticulitis. A total of 50 patients were included in the analysis, 20 (study group) had received 3.2 g/d of mesalamine starting from the day of admission in addition to the usual standard treatment, 30 (control group) had received standard therapy alone. Data was retrieved from a prospective database. Our primary study endpoints were: C reactive protein mean levels over time and their variation from baseline (ΔCRP) over the first three days of treatment. Secondary end points included: mean white blood cell and neutrophile count over time, time before regaining of regular bowel movements (passing of stools), time before reintroduction of food intake, intensity of lower abdominal pain over time, analgesic consumption and length of hospital stay. Patients characteristics and inflammatory parameters were similar at baseline in the two groups. The evaluation of CRP levels over time showed, in treated patients, a distinct trend towards a faster decrease compared to controls. This difference approached statistical significance on day 2 (mean CRP 6.0 +/- 4.2 mg/dL and 10.0 +/- 6.7 mg/dL respectively in study group vs controls, P = 0.055). ΔCRP evaluation evidenced a significantly greater increment of this inflammatory marker in the control group on day 1 (P = 0.03). A similar trend towards a faster resolution of inflammation was observed evaluating the total white blood cell count. Neutrophile levels were significantly lower in treated patients on day 2 and on day 3 (P diverticulitis.

  20. Inflammatory Responses in a Benign Prostatic Hyperplasia Epithelial Cell Line (BPH-1) Infected with Trichomonas vaginalis.

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    Kim, Sang-Su; Kim, Jung-Hyun; Han, Ik-Hwan; Ahn, Myoung-Hee; Ryu, Jae-Sook

    2016-04-01

    Trichomonas vaginalis causes the most prevalent sexually transmitted infection worldwide. Trichomonads have been detected in prostatic tissues from prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer. Chronic prostatic inflammation is known as a risk factor for prostate enlargement, benign prostatic hyperplasia symptoms, and acute urinary retention. Our aim was to investigate whether T. vaginalis could induce inflammatory responses in cells of a benign prostatic hyperplasia epithelial cell line (BPH-1). When BPH-1 cells were infected with T. vaginalis, the protein and mRNA of inflammatory cytokines, such as CXCL8, CCL2, IL-1β, and IL-6, were increased. The activities of TLR4, ROS, MAPK, JAK2/STAT3, and NF-κB were also increased, whereas inhibitors of ROS, MAPK, PI3K, NF-κB, and anti-TLR4 antibody decreased the production of the 4 cytokines although the extent of inhibition differed. However, a JAK2 inhibitor inhibited only IL-6 production. Culture supernatants of the BPH-1 cells that had been incubated with live T. vaginalis (trichomonad-conditioned medium, TCM) contained the 4 cytokines and induced the migration of human monocytes (THP-1 cells) and mast cells (HMC-1 cells). TCM conditioned by BPH-1 cells pretreated with NF-κB inhibitor showed decreased levels of cytokines and induced less migration. Therefore, it is suggested that these cytokines are involved in migration of inflammatory cells. These results suggest that T. vaginalis infection of BPH patients may cause inflammation, which may induce lower urinary tract symptoms (LUTS).

  1. Eggs modulate the inflammatory response to carbohydrate restricted diets in overweight men

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    Volek Jeff S

    2008-02-01

    Full Text Available Abstract Background Carbohydrate restricted diets (CRD consistently lower glucose and insulin levels and improve atherogenic dyslipidemia [decreasing triglycerides and increasing HDL cholesterol (HDL-C]. We have previously shown that male subjects following a CRD experienced significant increases in HDL-C only if they were consuming a higher intake of cholesterol provided by eggs compared to those individuals who were taking lower concentrations of dietary cholesterol. Here, as a follow up of our previous study, we examined the effects of eggs (a source of both dietary cholesterol and lutein on adiponectin, a marker of insulin sensitivity, and on inflammatory markers in the context of a CRD. Methods Twenty eight overweight men [body mass index (BMI 26–37 kg/m2] aged 40–70 y consumed an ad libitum CRD (% energy from CHO:fat:protein = 17:57:26 for 12 wk. Subjects were matched by age and BMI and randomly assigned to consume eggs (EGG, n = 15 (640 mg additional cholesterol/day provided by eggs or placebo (SUB, n = 13 (no additional dietary cholesterol. Fasting blood samples were drawn before and after the intervention to assess plasma lipids, insulin, adiponectin and markers of inflammation including C-reactive protein (CRP, tumor necrosis factor-alpha (TNF-α, interleukin-8 (IL-8, monocyte chemoattractant protein-1 (MCP-1, intercellular adhesion molecule-1 (ICAM-1, and vascular cell adhesion molecule-1(VCAM-1. Results Body weight, percent total body fat and trunk fat were reduced for all subjects after 12 wk (P Conclusion A CRD with daily intake of eggs decreased plasma CRP and increased plasma adiponectin compared to a CRD without eggs. These findings indicate that eggs make a significant contribution to the anti-inflammatory effects of CRD, possibly due to the presence of cholesterol, which increases HDL-C and to the antioxidant lutein which modulates certain inflammatory responses.

  2. Ginsenoside Rd attenuates early oxidative damage and sequential inflammatory response after transient focal ischemia in rats.

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    Ye, Ruidong; Yang, Qianzi; Kong, Xiangwei; Han, Junliang; Zhang, Xiao; Zhang, Yunxia; Li, Ping; Liu, Juanfang; Shi, Ming; Xiong, Lize; Zhao, Gang

    2011-02-01

    We previously found that ginsenoside Rd (Rd), one of the main active ingredients in Panax ginseng, attenuates neuronal oxidative damage in vitro induced by hydrogen peroxide and oxygen-glucose deprivation. In this study, we sought to investigate the potential protective effects and associated mechanisms of Rd in a rat model of focal cerebral ischemia. Rats administered with Rd (0.1-200mg/kg) or vehicle was subjected to transient middle cerebral artery occlusion. Rd at the dose of 10-50mg/kg significantly reduced the infarct volume and improved the long-term neurological outcome up to 6 weeks after ischemia. To evaluate the underlying mechanisms, in vivo free radical generation was monitored using microdialysis, oxidative DNA damage was identified by 8-hydroxy-deoxyguanosine immunostaining, oxidative protein damage was identified by the assessment of protein carbonyl and advanced glycosylation end products, and lipid peroxidation was estimated by determining the malondialdehyde and 4-hydroxynonenal formations. Microdialysis results displayed a prominent inhibitory effect of Rd on the hydroxy radical formation trapped as 2,3- and 2,5-DHBA. Early accumulations of DNA, protein and lipid peroxidation products were also suppressed by Rd treatment. Although Rd partly preserved endogenous antioxidant activities in the ischemic penumbra, in sham rats without stroke, endogenous antioxidant activities were not affected by Rd. Furthermore, we assayed sequential inflammatory response in a later phase after ischemia. Rd significantly eliminated inflammatory injury as indicated by the suppression of microglial activation, inducible nitric oxide synthase and cyclooxygenase-2 expression. Collectively, these findings demonstrated that Rd exerts neuroprotection in transient focal ischemia, which may involve early free radicals scavenging pathway and a late anti-inflammatory effect. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Age-associated changes in immune and inflammatory responses: impact of vitamin E intervention.

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    Wu, Dayong; Meydani, Simin Nikbin

    2008-10-01

    Aging is associated with dysregulated immune and inflammatory responses. Declining T cell function is the most significant and best-characterized feature of immunosenescence. Intrinsic changes within T cells and extrinsic factors contribute to the age-associated decline in T cell function. T cell defect seen in aging involves multiple stages from early receptor activation events to clonal expansion. Among extrinsic factors, increased production of T cell-suppressive factor PGE(2) by macrophages (Mphi) is most recognized. Vitamin E reverses an age-associated defect in T cells, particularly naïve T cells. This effect of vitamin E is also reflected in a reduced rate of upper respiratory tract infection in the elderly and enhanced clearance of influenza infection in a rodent model. The T cell-enhancing effect of vitamin E is accomplished via its direct effect on T cells and indirectly by inhibiting PGE(2) production in Mphi. Up-regulated inflammation with aging has attracted increasing attention as a result of its implications in the pathogenesis of diseases. Increased PGE(2) production in old Mphi is a result of increased cyclooxygenase 2 (COX-2) expression, leading to higher COX enzyme activity, which in turn, is associated with the ceramide-induced up-regulation of NF-kappaB. Similar to Mphi, adipocytes from old mice have a higher expression of COX-2 as well as inflammatory cytokines IL-1beta, IL-6, and TNF-alpha, which might also be related to elevated levels of ceramide and NF-kappaB activation. This review will discuss the above age-related immune and inflammatory changes and the effect of vitamin E as nutritional intervention with a focus on the work conducted in our laboratory.

  4. Croton antisyphiliticus Mart. attenuates the inflammatory response to carrageenan-induced pleurisy in mice.

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    Dos Reis, Gustavo Oliveira; Vicente, Geison; de Carvalho, Francieli Kanumfre; Heller, Melina; Micke, Gustavo Amadeu; Pizzolatti, Moacir Geraldo; Fröde, Tânia Silvia

    2014-04-01

    The aim of this study was to investigate the anti-inflammatory effect of the crude hydroalcoholic extract (CHE) from the aerial parts of Croton antisyphiliticus, its fractions and isolated compounds derived from it on the mouse model of pleurisy induced by carrageenan. The aerial parts of C. antisyphiliticus were dried, macerated and extracted with ethanol to obtain the CHE, which was fractionated by liquid-liquid extraction using solvents with increasing polarity to obtain hexane (Hex), ethyl acetate (EA) and aqueous (Aq) fractions. Vitexin and quinic acid were isolated from Aq fraction. Capillary electrophoresis analysis, physical characteristics and spectral data produced by infrared (IR), nuclear magnetic resonance ((1)H and (13)C NMR) and mass spectrometry analyses were used to identify and elucidate the structure of the isolated compounds. The experimental model of pleurisy was induced in mice by a single intrapleural injection of carrageenan (1 %). Leukocytes, exudate concentrations, myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities and nitrate/nitrite (NOx), tumor necrosis factor-α (TNF-α) and interleukin-17 (IL-17) levels were determined in the pleural fluid leakage at 4 h after pleurisy induction. Animals pre-treated with CHE, Hex, EA, Aq, vitexin and quinic acid exhibited decreases in leukocytes, exudate concentrations, MPO and ADA activities and NOx levels (p < 0.05). Also CHE, Hex, EA and vitexin but not quinic acid inhibited TNF-α and IL-17 levels (p < 0.05). C. antisyphiliticus caused anti-inflammatory effect by inhibiting the activated leukocytes, exudate concentrations, NOx, TNF-α, and IL-17 levels. The compounds vitexin and quinic acid may be responsible for this anti-inflammatory action.

  5. Haematological, inflammatory, and immunological responses in elite judo athletes maintaining high training loads during Ramadan.

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    Chaouachi, Anis; Coutts, Aaron J; Wong, Del P; Roky, Rachida; Mbazaa, Abderraouf; Amri, Mohamed; Chamari, Karim

    2009-10-01

    During Ramadan, Muslims abstain from food and fluid intake from dawn to sunset for 1 month. These behavioural changes that accompany Ramadan may impact upon Muslim athletes who continue to train intensely. The aim of the present study was to evaluate the effect of Ramadan intermittent fasting (RIF) on the haematological, inflammatory, and immunological measures in elite judo athletes maintaining their usual high training loads. Haematological markers of inflammation, hormones, and immune status were studied in 15 elite male judo athletes before, during, and after Ramadan. The RIF produced small but significant changes in inflammatory, hormonal, and immunological profiles in judo athletes. Serum C-reactive protein increased from 2.93 +/- 0.26 mg.L-1 pre-Ramadan to 4.60 +/- 0.51 mg.L-1 at the end of Ramadan. Haptoglobin and antitrypsin also significantly increased at different phases during Ramadan, whereas homocysteine and prealbumin remained relatively unchanged. Albumin decreased slightly by mid-Ramadan, then recovered. Immunoglobulin Aincreased from 1.87 +/- 0.56 g.L-1 before Ramadan to 2.49 +/- 0.75 g.L-1 at the end, and remained high 3 weeks after. There were no changes in the leucocyte cell counts throughout the study. The mean blood level of thyroid-stimulating hormone and free thyroxine increased significantly during RIF. Most of these changes were within the normal ranges. These results suggest that athletes who continue to train intensely during Ramadan are liable to experience a myriad of small fluctuations in hormones, immunoglobulins, antioxidants, and inflammatory responses.

  6. Effect of sustained maternal responsivity on later vocabulary development in children with fragile X syndrome.

    Science.gov (United States)

    Brady, Nancy; Warren, Steven F; Fleming, Kandace; Keller, Juliana; Sterling, Audra

    2014-02-01

    This research explored whether sustained maternal responsivity (a parent–child interaction style characterized by warmth, nurturance, and stability as well as specific behaviors, such as contingent positive responses to child initiations) was a significant variable predicting vocabulary development of children with fragile X syndrome through age 9 years. Fifty-five mother–child dyads were followed longitudinally when children were between 2 and 10 years of age. Measures of maternal responsivity and child vocabulary were obtained at regular intervals starting at age 2.9 years. Sustained responsivity was indicated by the average responsivity measured over Observations 2–5. Responsivity at the 1st time period, autism symptoms, and cognitive development were used as control variables. After controlling for development and autism symptoms, the authors found significant effects for sustained responsivity on receptive vocabulary, expressive vocabulary, and the rate of different words children produced through age 9. Maternal responsivity, which is typically a variable of interest during early childhood, continues to be a significant variable, predicting vocabulary development through the middle childhood period. Thus, responsivity is a potential target for language interventions through this age period.

  7. The effect of sustained maternal responsivity on later vocabulary development in children with Fragile X Syndrome

    Science.gov (United States)

    Brady, Nancy; Warren, Steven F.; Fleming, Kandace; Keller, Juliana; Sterling, Audra

    2013-01-01

    Purpose The research question addressed was whether sustained maternal responsivity (a parent-child interaction style characterized by warmth, nurturance and stability as well as specific behaviors such as contingent positive responses to child initiations) was a significant variable predicting vocabulary development of children with FXS through age 9 years. Method Fifty-five mother-child dyads were followed longitudinally when children were between 2 and 10 years of age. Measures of maternal responsivity and child vocabulary were obtained at regular intervals starting at age 2.9 years. Sustained responsivity was indicated by the average responsivity measured over observations 2–5. Responsivity at the first time period, autism symptoms, and cognitive development were used as control variables. Results After controlling for development and autism symptoms, we found significant effects for sustained responsivity on receptive vocabulary, expressive vocabulary, and the rate of different words children produced through age 9. Conclusions Maternal responsivity, which is typically a variable of interest during early childhood, continues to be a significant variable, predicting vocabulary development through the middle childhood period. Thus, responsivity is a potential target for language interventions through this age period. PMID:24023370

  8. Suppression of inflammatory responses of human gingival fibroblasts by gingipains from Porphyromonas gingivalis.

    Science.gov (United States)

    Palm, E; Khalaf, H; Bengtsson, T

    2015-02-01

    The interaction between human gingival fibroblasts (HGFs) and Porphyromonas gingivalis plays an important role in the development and progression of periodontitis. Porphyromonas gingivalis possesses several virulence factors, including cysteine proteases, the arginine-specific (Rgp) and lysine-specific (Kgp) gingipains. Studying the mechanisms that P. gingivalis, and its derived virulence, use to propagate and interact with host cells will increase the understanding of the development and progression of periodontitis. In this study, we aimed to elucidate how P. gingivalis influences the inflammatory events in HGFs regarding transforming growth factor-β1 (TGF-β1 ), CXCL8, secretory leucocyte protease inhibitor (SLPI), c-Jun and indoleamine 2,3-dioxygenase (IDO). HGFs were inoculated for 6 and 24 h with the wild-type strains ATCC 33277 and W50, two gingipain-mutants of W50 and heat-killed ATCC 33277. The P. gingivalis regulated CXCL8 and TGF-β1 in HGFs, and the kgp mutant gave significantly higher immune response with increased CXCL8 (P gingivalis (P gingivalis contributes to the tissue destruction associated with periodontitis. Furthermore, we found that P. gingivalis inhibits the expression of the antimicrobial IDO, as well as upregulating c-Jun (P gingivalis both triggers and suppresses the immune response in HGFs. Consequently, we suggest that the pathogenic effects of P. gingivalis, and especially the activity of the gingipains on the inflammatory and immune response of HGFs, are crucial in periodontitis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Endotoxin induced peritonitis elicits monocyte immigration into the lung: implications on alveolar space inflammatory responsiveness

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    Welte Tobias

    2006-02-01

    Full Text Available Abstract Background Acute peritonitis developing in response to gram-negative bacterial infection is known to act as a trigger for the development of acute lung injury which is often complicated by the development of nosocomial pneumonia. We hypothesized that endotoxin-induced peritonitis provokes recruitment of monocytes into the lungs, which amplifies lung inflammatory responses to a second hit intra-alveolar challenge with endotoxin. Methods Serum and lavage cytokines as well as bronchoalveolar lavage fluid cells were analyzed at different time points after intraperitoneal or intratracheal application of LPS. Results We observed that mice challenged with intraperitoneal endotoxin developed rapidly increasing serum and bronchoalveolar lavage fluid (BALF cytokine and chemokine levels (TNFα, MIP-2, CCL2 and a nearly two-fold expansion of the alveolar macrophage population by 96 h, but this was not associated with the development of neutrophilic alveolitis. In contrast, expansion of the alveolar macrophage pool was not observed in CCR2-deficient mice and in wild-type mice systemically pretreated with the anti-CD18 antibody GAME-46. An intentional two-fold expansion of alveolar macrophage numbers by intratracheal CCL2 following intraperitoneal endotoxin did not exacerbate the development of acute lung inflammation in response to intratracheal endotoxin compared to mice challenged only with intratracheal endotoxin. Conclusion These data, taken together, show that intraperitoneal endotoxin triggers a CCR2-dependent de novo recruitment of monocytes into the lungs of mice but this does not result in an accentuation of neutrophilic lung inflammation. This finding represents a previously unrecognized novel inflammatory component of lung inflammation that results from endotoxin-induced peritonitis.

  10. Dihydroxyselenolane (DHS) supplementation improves survival following whole-body irradiation (WBI) by suppressing tissue-specific inflammatory responses.

    Science.gov (United States)

    Kunwar, Amit; Verma, Prachi; Bhilwade, H N; Iwaoka, Michio; Priyadarsini, K Indira

    2016-09-01

    Dihydroxyselenolane (DHS), a simple water-soluble organoselenium compound, was evaluated for radioprotection in BALB/c mice after whole-body irradiation (WBI) (8Gy (60)Co, 1Gy/min), by monitoring 30-d post-irradiation survival and biochemical/histological changes in radiosensitive organs. Intraperitoneal administration of DHS at 2mg/kg for five consecutive days before irradiation and three times per week during the post-irradiation period showed maximum benefit (40% improvement in 30 d post-irradiation survival). DHS treatment, despite inducing expression of glutathione peroxidases (GPx1, GPx2, and GPx4) in spleen and intestine, did not protect against radiation-induced acute (10-day) haematopoietic and gastrointestinal toxicities. DHS treatment significantly reduced radiation-induced DNA damage in peripheral leukocytes and inflammatory responses in intestine, lung, and circulation. The anti-inflammatory effect of DHS was associated with reductions in lipid peroxidation, expression of pro-inflammatory genes such as Icam-1, Ccl-2, and iNos-2, and subsequent infiltration of inflammatory cells. Irradiated mice treated with DHS survived until day 30 post-irradiation and showed restoration of spleen cellularity and intestinal villi, but had moderately increased systemic and tissue-specific inflammatory responses. Another organoselenium compound, selenomethionine, evaluated in parallel with DHS at the same dose and treatment schedule, showed comparable radioprotective effects. The mechanism of radioprotection by DHS is mainly via suppression of inflammatory responses. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. The Acute Inflammatory Response in Trauma/Hemorrhage and Traumatic Brain Injury : Current State and Emerging Prospects

    NARCIS (Netherlands)

    Namas, R.; Ghuma, A.; Hermus, L.; Zamora, R.; Okonkwo, D. O.; Billiar, T. R.; Vodovotz, Y.

    2009-01-01

    Traumatic injury/hemorrhagic shock (T/HS) elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases including T/HS and traumatic brain injury

  12. Acute Exercise-Induced Mitochondrial Stress Triggers an Inflammatory Response in the Myocardium via NLRP3 Inflammasome Activation with Mitophagy.

    Science.gov (United States)

    Li, Haiying; Miao, Weiguo; Ma, Jingfen; Xv, Zhen; Bo, Hai; Li, Jianyu; Zhang, Yong; Ji, Li Li

    2016-01-01

    Increasing evidence has indicated that acute strenuous exercise can induce a range of adverse reactions including oxidative stress and tissue inflammation. However, little is currently known regarding the mechanisms that underlie the regulation of the inflammatory response in the myocardium during acute heavy exercise. This study evaluated the mitochondrial function, NLRP3 inflammasome activation, and mitochondrial autophagy-related proteins to investigate the regulation and mechanism of mitochondrial stress regarding the inflammatory response of the rat myocardium during acute heavy exercise. The results indicated that the mitochondrial function of the myocardium was adaptively regulated to meet the challenge of stress during acute exercise. The exercise-induced mitochondrial stress also enhanced ROS generation and triggered an inflammatory reaction via the NLRP3 inflammasome activation. Moreover, the mitochondrial autophagy-related proteins including Beclin1, LC3, and Bnip3 were all significantly upregulated during acute exercise, which suggests that mitophagy was stimulated in response to the oxidative stress and inflammatory response in the myocardium. Taken together, our data suggest that, during acute exercise, mitochondrial stress triggers the rat myocardial inflammatory response via NLRP3 inflammasome activation and activates mitophagy to minimize myocardial injury.

  13. Annexin A2 Modulates ROS and Impacts Inflammatory Response via IL-17 Signaling in Polymicrobial Sepsis Mice.

    Directory of Open Access Journals (Sweden)

    Sisi He

    2016-07-01

    Full Text Available Sepsis is a progressive disease manifesting excessive inflammatory responses, severe tissue injury, organ dysfunction, and, ultimately, mortality. Since currently, there are limited therapeutic options for this disease, further understanding the molecular pathogenesis of sepsis may help develop effective treatments. Here we identify a novel role for Annexin A2 (AnxA2, a multi-compartmental protein, in inhibiting pro-inflammatory response by regulating reactive oxygen species (ROS and IL-17 signaling during sepsis. In cecal ligation and puncture (CLP sepsis models, anxa2-/- mice manifested increased pro-inflammatory cytokines and neutrophil infiltration, but decreased bacterial clearance and animal survival. In addition, AnxA2 deficiency led to intensified ROS and IL-17A. Using site directed mutagenesis, we uncovered that cysteine 9 of AnxA2 was the most important aa (site for regulation of ROS levels. Furthermore, ROS appears to be responsible for elevated IL-17A levels and subsequently exaggerated inflammatory response. Depletion of IL-17 via CRISPR/Cas9 KO strategy down-regulated inflammation and conferred protection against sepsis in anxa2-/- mice. Our findings reveal a previously undemonstrated function for AnxA2 in inflammatory response in polymicrobial sepsis models via an AnxA2-ROS-IL-17 axis, providing insight into the regulation of pathophysiology of sepsis.

  14. Post-treatment vascular leakage and inflammatory responses around brain cysts in porcine neurocysticercosis.

    Directory of Open Access Journals (Sweden)

    Siddhartha Mahanty

    2015-03-01

    Full Text Available Cysticidal treatment of neurocysticercosis, an infection of humans and pig brains with Taenia solium, results in an early inflammatory response directed to cysts causing seizures and focal neurological manifestations. Treatment-induced pericystic inflammation and its association with blood brain barrier (BBB dysfunction, as determined by Evans blue (EB extravasation, was studied in infected untreated and anthelmintic-treated pigs. We compared the magnitude and extent of the pericystic inflammation, presence of EB-stained capsules, the level of damage to the parasite, expression of genes for proinflammatory and regulatory cytokines, chemokines, and tissue remodeling by quantitative PCR assays between treated and untreated infected pigs and between EB-stained (blue and non stained (clear cysts. Inflammatory scores were higher in pericystic tissues from EB-stained cysts compared to clear cysts from untreated pigs and also from anthelmintic-treated pigs 48 hr and 120 hr after treatment. The degree of inflammation correlated with the severity of cyst wall damage and both increased significantly at 120 hours. Expression levels of the proinflammatory genes for IL-6, IFN-γ, TNF-α were higher in EB-stained cysts compared to clear cysts and unaffected brain tissues, and were generally highest at 120 hr. Additionally, expression of some markers of immunoregulatory activity (IL-10, IL-2Rα were decreased in EB-stained capsules. An increase in other markers for regulatory T cells (CTLA4, FoxP3 was found, as well as significant increases in expression of two metalloproteases, MMP1 and MMP2 at 48 hr and 120 hr post-treatment. We conclude that the increase in severity of the inflammation caused by treatment is accompanied by both a proinflammatory and a complex regulatory response, largely limited to pericystic tissues with compromised vascular integrity. Because treatment induced inflammation occurs in porcine NCC similar to that in human cases, this model

  15. Holi colours contain PM10 and can induce pro-inflammatory responses.

    Science.gov (United States)

    Bossmann, Katrin; Bach, Sabine; Höflich, Conny; Valtanen, Kerttu; Heinze, Rita; Neumann, Anett; Straff, Wolfgang; Süring, Katrin

    2016-01-01

    At Holi festivals, originally celebrated in India but more recently all over the world, people throw coloured powder (Holi powder, Holi colour, Gulal powder) at each other. Adverse health effects, i.e. skin and ocular irritations as well as respiratory problems may be the consequences. The aim of this study was to uncover some of the underlying mechanisms. We analysed four different Holi colours regarding particle size using an Electric field cell counting system. In addition, we incubated native human cells with different Holi colours and determined their potential to induce a pro-inflammatory response by quantifying the resulting cytokine production by means of ELISA (Enzyme Linked Immunosorbent Assay) and the resulting leukocyte oxidative burst by flow cytometric analysis. Moreover, we performed the XTT (2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) and Propidium iodide cytotoxicity tests and we measured the endotoxin content of the Holi colour samples by means of the Limulus Amebocyte Lysate test (LAL test). We show here that all tested Holi colours consist to more than 40 % of particles with an aerodynamic diameter smaller than 10 μm, so called PM10 particles (PM, particulate matter). Two of the analysed Holi powders contained even more than 75 % of PM10 particles. Furthermore we demonstrate in cell culture experiments that Holi colours can induce the production of the pro-inflammatory cytokines TNF-α (Tumor necrosis factor-α), IL-6 (Interleukine-6) and IL-1β (Interleukine-1β). Three out of the four analysed colours induced a significantly higher cytokine response in human PBMCs (Peripheral Blood Mononuclear Cells) and whole blood than corn starch, which is often used as carrier substance for Holi colours. Moreover we show that corn starch and two Holi colours contain endotoxin and that certain Holi colours display concentration dependent cytotoxic effects in higher concentration. Furthermore we reveal that in principle Holi

  16. Post-treatment vascular leakage and inflammatory responses around brain cysts in porcine neurocysticercosis.

    Science.gov (United States)

    Mahanty, Siddhartha; Orrego, Miguel Angel; Mayta, Holger; Marzal, Miguel; Cangalaya, Carla; Paredes, Adriana; Gonzales-Gustavson, Eloy; Arroyo, Gianfranco; Gonzalez, Armando E; Guerra-Giraldez, Cristina; García, Hector H; Nash, Theodore E

    2015-03-01

    Cysticidal treatment of neurocysticercosis, an infection of humans and pig brains with Taenia solium, results in an early inflammatory response directed to cysts causing seizures and focal neurological manifestations. Treatment-induced pericystic inflammation and its association with blood brain barrier (BBB) dysfunction, as determined by Evans blue (EB) extravasation, was studied in infected untreated and anthelmintic-treated pigs. We compared the magnitude and extent of the pericystic inflammation, presence of EB-stained capsules, the level of damage to the parasite, expression of genes for proinflammatory and regulatory cytokines, chemokines, and tissue remodeling by quantitative PCR assays between treated and untreated infected pigs and between EB-stained (blue) and non stained (clear) cysts. Inflammatory scores were higher in pericystic tissues from EB-stained cysts compared to clear cysts from untreated pigs and also from anthelmintic-treated pigs 48 hr and 120 hr after treatment. The degree of inflammation correlated with the severity of cyst wall damage and both increased significantly at 120 hours. Expression levels of the proinflammatory genes for IL-6, IFN-γ, TNF-α were higher in EB-stained cysts compared to clear cysts and unaffected brain tissues, and were generally highest at 120 hr. Additionally, expression of some markers of immunoregulatory activity (IL-10, IL-2Rα) were decreased in EB-stained capsules. An increase in other markers for regulatory T cells (CTLA4, FoxP3) was found, as well as significant increases in expression of two metalloproteases, MMP1 and MMP2 at 48 hr and 120 hr post-treatment. We conclude that the increase in severity of the inflammation caused by treatment is accompanied by both a proinflammatory and a complex regulatory response, largely limited to pericystic tissues with compromised vascular integrity. Because treatment induced inflammation occurs in porcine NCC similar to that in human cases, this model can be used to

  17. Inflammatory response to acute exposure to welding fumes during the working day

    Directory of Open Access Journals (Sweden)

    Merja Järvelä

    2013-04-01

    Full Text Available Objectives: To investigate cardiorespiratory and inflammatory responses in male workers following exposure to welding fumes and airborne particles in actual workplace conditions. Materials and Methods: We measured blood leukocytes and their differential counts, platelet count, hemoglobin, sensitive C-reactive protein, fibrinogen, E-selectin, IL-(interleukin1β, IL-6, IL-8, tumor necrosis factor alpha (TNF-α and endothelin-1 in blood samples of twenty workers before and after their working day. We also studied peak expiratory flow (PEF, forced expiratory volume in one second (FEV1, and exhaled nitric oxide (NO. We assessed heart rate variability (HRV by obtaining 24-hour ambulatory electrocardiograms. Results: The total blood leukocytes and neutrophils increased after the work shift, whereas IL-1β and E-selectin decreased significantly. There were no tatistically significant changes in exhaled NO, FEV1, PEF or HRV. Conclusion: Occupational exposure to welding fumes and particles caused a slight, acute inflammatory effect estimated based on the increased values of leukocytes and neutrophils in blood and a decrease in the interleukin 1β and E-selectin values, but no changes in the pulmonary function (exhaled NO, FEV1, PEF or HRV during the working day were observed.

  18. Umbilical arteritis and phlebitis mark different stages of the fetal inflammatory response.

    Science.gov (United States)

    Kim, C J; Yoon, B H; Romero, R; Moon, J B; Kim, M; Park, S S; Chi, J G

    2001-08-01

    Funisitis, the inflammation of the umbilical cord determined by histologic examination of the placenta, is evidence of a fetal inflammatory response. The inflammatory process may involve the umbilical vein (phlebitis) and one or both umbilical arteries (arteritis) and extend into the Wharton's jelly. This study was conducted to examine whether the pattern of inflammation of the umbilical cord correlates with a biochemical marker of systemic fetal inflammation (umbilical cord plasma interleukin-6) and an adverse neonatal outcome. This cohort study included 636 cases of preterm delivery (jelly. Umbilical cord plasma interleukin-6 concentrations were assayed by a sensitive and specific immunoassay. Neonates with umbilical arteritis had a significantly higher median concentration of cord plasma interleukin-6 (median, 111 pg/mL; range, 0.1-19,230 pg/mL) than those without umbilical arteritis (median, 22.5 pg/mL; range, 0.9-511.6 pg/mL; P jelly, was associated with the highest median concentration of plasma interleukin-6 observed in this study (median, 182.6 pg/mL; range, 0.1-7,400 pg/mL), whereas inflammation limited to the vein (phlebitis) was associated with a lower concentration of cord plasma interleukin-6 (median, 29.1 pg/mL; range, 0.9-511.6 pg/mL; P <.05). Neonates whose placenta demonstrates umbilical arteritis have higher concentrations of umbilical cord plasma interleukin-6 and higher rates of adverse outcome than those without umbilical arteritis.

  19. Neuromuscular and inflammatory responses to handball small-sided games: the effects of physical contact.

    Science.gov (United States)

    Dello Iacono, A; Eliakim, A; Padulo, J; Laver, L; Ben-Zaken, S; Meckel, Y

    2017-10-01

    The aim of this study was to investigate the influence of physical contact on neuromuscular impairments and inflammatory response during handball small-sided games. Using a counterbalanced design, 12 elite male junior handball players were divided into two groups: contact (C-SSG) and no-contact (NC-SSG), performing both contact and no-contact small-sided games, in reverse order on two training sessions separated by 5 days. The methodology and rules were identical for the two SSG regimens, with the only difference being the inclusion or prohibition of upper body use for physical contacts. Upper and lower body neuromuscular performances and blood concentrations of inflammatory cytokine IL-6 were assessed before and immediately after the games. During small-sided games, video analysis was used to establish the physical contact counts. Significant differences were found in most upper and lower limbs muscles kinetic variables and in the physical contact events (all P handball players. These outcomes outline the specific physiological profile of C-SSG that, in turn, might be used by practitioners and coaches as a practical approach to strategically select exercises in athlete's overall training program. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Proteomics of inflammatory and oxidative stress response in cows with subclinical and clinical mastitis.

    Science.gov (United States)

    Turk, Romana; Piras, Cristian; Kovačić, Mislav; Samardžija, Marko; Ahmed, Hany; De Canio, Michele; Urbani, Andrea; Meštrić, Zlata Flegar; Soggiu, Alessio; Bonizzi, Luigi; Roncada, Paola

    2012-07-19

    Cow serum proteome was evaluated by three different complementary approaches in the control group, subclinical and clinical mastitis in order to possibly find differential protein expression useful for a better understanding of the pathophysiology of mastitis as well as for an early diagnosis of the disease. The systemic inflammatory and oxidative stress response in cows with subclinical and clinical mastitis were observed. The collected evidence shows a differential protein expression of serpin A3-1, vitronectin-like protein and complement factor H in subclinical mastitis in comparison with the control. It was also found a differential protein expression of inter-alpha-trypsin inhibitor heavy chain H4, serpin A3-1, C4b-binding protein alpha chain, haptoglobin and apolipoprotein A-I in clinical mastitis compared to the control. Among the inflammatory proteins up-regulated in clinical mastitis, vitronectin is over-expressed in both subclinical and clinical mastitis indicating a strong bacterial infection. This suggests vitronectin as an important mediator in the pathogenesis of the onset of mastitis as well as a valuable marker for diagnosis of the subclinical form of the disease. Obtained data could be useful for the detection of mastitis during the subclinical phase and for a better comprehension of the pathophysiological mechanisms involved in the onset of the disease. Copyright © 2012 Elsevier B.V. All rights reserved.