Relation Between Interleukin-1-β And Interleukin-8 Levels In Breast Milk (Colostrum) And Neonatal Physiological Jaundice

International Nuclear Information System (INIS)

Mohamed, A.A.; Moawad, A.T.; Marei, E.S.

2011-01-01

The immune system of neonates is influenced by maternal immunity during pregnancy and lactation. Breast-fed neonates have higher incidence of neonatal jaundice and higher level of total serum bilirubin than formula-fed infants. The aim of this study was to find a relationship between neonatal physiological jaundice and interleukin-1-beta (IL-1-β) and interleukin-8 (IL-8) in the colostrum of nursing mothers. Breast milk (colostrum) was collected from 45 nursing mothers of healthy full term neonates. The sharing mothers and their neonates were divided into two groups according to the presence of neonatal jaundice and the level of total serum bilirubin. All jaundiced neonates had total serum bilirubin level more than 12 mg/dl which appeared on the third postpartum day, all of them were breast-fed only. They were subjected to full history through clinical examination and laboratory investigations including determination of colostral levels of IL-1-β and IL-8, by ELISA, and determination of neonatal total serum bilirubin levels. This study revealed that mothers of neonates with physiological jaundice had higher concentrations of IL-1-β and IL-8 in their colostrums as compared with control group. Moreover, it displayed that total serum bilirubin level of jaundiced neonates was higher than its level in non-jaundiced neonates. There were significant correlations between IL- 1-β and IL-8 with mother's age in all groups, while there were inverse correlations between IL-1-β, IL-8 and gestational age of non- jaundiced neonates. Additionally, there was significant correlation between IL-1-β and IL-8 in the colostrum of all mothers enrolled in this study. On the other hand, no correlation was determined between cytokines IL-1-β, IL-8 and total serum bilirubin in all neonates sharing in this study. This study clearly demonstrated that the levels of immunomodulating agents such as cytokines IL-1-β and IL-8 were elevated in the colostrum of mothers with jaundiced neonates

A ROLE FOR INTERLEUKIN 8 IN DIRECT REGULATION OF T CELL FUNCTIONAL ACTIVITY

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M. E. Meniailo

2017-01-01

Full Text Available CD3+T lymphocytes were isolated from normal donors by positive magnetic separation. Activation of the T cells with particles conjugated with antibodies to CD3, СD28 and СD2 molecules led to substantial increase in T cell production of interleukin-8 (IL-8. An interleukin-8 receptor (CXCR1, CD181 was initially expressed in 13.3% of T lymphocytes. Activation of T lymphocytes resulted into a detectable increase of CD181+ cell number among CD4+ naïve cells and CD4+ terminally-differentiated effector cells, and, conversely, into decrease of their number among CD4+ effector memory cells. Activation of T lymphocytes was assessed by membrane expression of CD25 molecule (receptor for IL-2. IL-8 (0.01-10.0 ng/ml was shown to markedly reduce activation of both CD4- and CD4+ effector memory T cells, as well as terminallydifferentiated T effectors, without significantly affecting activation of naive T lymphocytes and central memory T cells. IL-8 noticeably increased IL-2 production by activated Т cells, caused a reduced IL-10 production, and did not significantly affect the secretion of IFNγ and IL-4. The data obtained suggest a significance of IL-8 for direct regulation of adaptive T cell responses.

Interleukin-8 stimulates progesterone production via the MEK pathway in ovarian theca cells.

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Shimizu, Takashi; Imamura, Eri; Magata, Fumie; Murayama, Chiaki; Miyamoto, Akio

2013-02-01

Interleukin 8 (IL-8) is a chemoattractant associated with ovulation in the mammalian ovary. This chemokine is also involved in the recruitment and activation of neutrophils. Using bovine tissue, we examined the possible role of IL-8 in steroid production by theca cells of the large ovarian follicles. IL-8 promoted progesterone production and stimulated StAR expression in cultured theca cells. The inhibitor of p38 did not disturb the P4 production and StAR expression in IL-8-treated theca cells. On the other hand, the inhibitor of MEK disturbed the P4 production and expression of StAR in theca cells treated with IL-8. These results suggest that IL-8 is associated with progesterone production in bovine theca cells via the MEK pathway.

Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment

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Kim, Jong-Hyuk, E-mail: jhkim@umn.edu [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); Frantz, Aric M.; Anderson, Katie L.; Graef, Ashley J.; Scott, Milcah C. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Robinson, Sally [Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Sharkey, Leslie C. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); O' Brien, Timothy D. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Dickerson, Erin B. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); Modiano, Jaime F., E-mail: modiano@umn.edu [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States)

2014-04-15

Interleukin-8 (IL-8) gene expression is highly up-regulated in canine hemangiosarcoma (HSA); however, its role in the pathogenesis of this disease is unknown. We investigated the expression of IL-8 in canine HSA tissues and cell lines, as well and the effects of IL-8 on canine HSA in vitro, and in vivo using a mouse xenograft model for the latter. Constitutive expression of IL-8 mRNA, IL-8 protein, and IL-8 receptor were variable among different tumor samples and cell lines, but they showed stable steady states in each cell line. Upon the addition of IL-8, HSA cells showed transient intracellular calcium fluxes, suggesting that their IL-8 receptors are functional and that IL-8 binding activates relevant signaling pathways. Yet, neither addition of exogenous IL-8 nor blockade of endogenous IL-8 by neutralizing anti-IL-8 antibody (α-IL-8 Ab) affected HSA cell proliferation or survival in vitro. To assess potential effects of IL-8 in other tumor constituents, we stratified HSA cell lines and whole tumor samples into “IL-8 high” and “IL-8 low” groups. Genome-wide gene expression profiling showed that samples in the “IL-8 high” tumor group were enriched for genes associated with a “reactive microenvironment,” including activation of coagulation, inflammation, and fibrosis networks. Based on these findings, we hypothesized that the effects of IL-8 on these tumors were mostly indirect, regulating interactions with the microenvironment. This hypothesis was supported by in vivo xenograft experiments where survival and engraftment of tumor cells was inhibited by administration of neutralizing α-IL-8 Ab. Together, our results suggest that IL-8 contributes to establishing a permissive microenvironment during the early stages of tumorigenesis in HSA. - Highlights: • IL-8 is expressed in canine hemangiosarcoma tumor samples and cell lines. • IL-8 transduces a relevant biological signal in canine hemangiosarcoma cells. • IL-8 gene signature is associated

Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment

International Nuclear Information System (INIS)

Kim, Jong-Hyuk; Frantz, Aric M.; Anderson, Katie L.; Graef, Ashley J.; Scott, Milcah C.; Robinson, Sally; Sharkey, Leslie C.; O'Brien, Timothy D.; Dickerson, Erin B.; Modiano, Jaime F.

2014-01-01

Interleukin-8 (IL-8) gene expression is highly up-regulated in canine hemangiosarcoma (HSA); however, its role in the pathogenesis of this disease is unknown. We investigated the expression of IL-8 in canine HSA tissues and cell lines, as well and the effects of IL-8 on canine HSA in vitro, and in vivo using a mouse xenograft model for the latter. Constitutive expression of IL-8 mRNA, IL-8 protein, and IL-8 receptor were variable among different tumor samples and cell lines, but they showed stable steady states in each cell line. Upon the addition of IL-8, HSA cells showed transient intracellular calcium fluxes, suggesting that their IL-8 receptors are functional and that IL-8 binding activates relevant signaling pathways. Yet, neither addition of exogenous IL-8 nor blockade of endogenous IL-8 by neutralizing anti-IL-8 antibody (α-IL-8 Ab) affected HSA cell proliferation or survival in vitro. To assess potential effects of IL-8 in other tumor constituents, we stratified HSA cell lines and whole tumor samples into “IL-8 high” and “IL-8 low” groups. Genome-wide gene expression profiling showed that samples in the “IL-8 high” tumor group were enriched for genes associated with a “reactive microenvironment,” including activation of coagulation, inflammation, and fibrosis networks. Based on these findings, we hypothesized that the effects of IL-8 on these tumors were mostly indirect, regulating interactions with the microenvironment. This hypothesis was supported by in vivo xenograft experiments where survival and engraftment of tumor cells was inhibited by administration of neutralizing α-IL-8 Ab. Together, our results suggest that IL-8 contributes to establishing a permissive microenvironment during the early stages of tumorigenesis in HSA. - Highlights: • IL-8 is expressed in canine hemangiosarcoma tumor samples and cell lines. • IL-8 transduces a relevant biological signal in canine hemangiosarcoma cells. • IL-8 gene signature is associated

Neonatal CD8+ T-cell differentiation is dependent on interleukin-12.

LENUS (Irish Health Repository)

McCarron, Mark J

2012-02-01

Neonatal CD8(+) T-cell activation is significantly impaired compared with that in adults. Recent studies have demonstrated that interleukin (IL)-12 is necessary as a third signal, in addition to antigen and co-stimulation, to authorize the differentiation of naive CD8(+) T cells. We examined whether human neonatal CD8(+) T cells, which possess an exclusively naive T-cell phenotype, required a third signal to authorize a productive T-cell response. IL-12 enhanced activated naive CD8(+) T-cell survival, expansion, CD25 expression, and IL-2 production. Activated CD8(+) T cells produced interferon-gamma and intracellular granzyme B and were cytotoxic only in the presence of IL-12. Sustained IL-12 signaling for 72 hours was required for optimal interferon-gamma production. IL-12, in concert with T cell receptor (TCR) stimulation, sustained late-stage (48-72 hours) intracellular phosphorylation and particularly total protein levels of the proximal TCR components, Lck, and CD3xi. The requirement for a third signal for productive human neonatal CD8(+) T-cell differentiation may have implications for neonatal vaccination strategies.

Evaluation of the role of leptin, interleukin-8 (Il-8) and nitric oxide (No) in children with insulin dependent diabetes mellitus (type 1)

International Nuclear Information System (INIS)

Ll-Nashar, N.A.; Abdel-Latif, A.; Mostafa, A.M.E.; Ahmed, S.M.

2005-01-01

The autoimmune nature of insulin dependent diabetes mellitus (IDDM), type 1, is well established. The documentation of altered Th 1/Th 2 balance and the finding of antibodies in the circulation directed against the b-cells can indicate the role of the immune system. The stimulating effect of insulin on leptin expression is well identified. The aim of this study is to investigate the profile and the relationships between leptin, interleukin-8 (IL-8) and nitric oxide (NO) and to reveal their possible role in the development and progression of IDDM. Serum leptin was evaluated using radioimmunoassay (RIA), serum concentration of IL-8 was assayed by enzyme linked immunosorbent assay (ELISA), while serum nitrite level (end product of NO) was determined by Griess reaction. The study was carried out on twenty IDDM children who compared with other twenty healthy non-diabetic ones with the same age and sex. The data revealed that children with IDDM established high weight-for-age (W/A)Z (P < 0.001) , high weight-for-height (W/H)Z (P < 0.05) and high glycated hemoglobin (HbA1c% ) (P < 0.0001). Both diabetic boys and girls showed higher serum leptin levels (7.48 ± 1.86 ng/ml) than the control group (5.92 ± 1.39 ng/ml). Leptin levels were higher in diabetic girls (8.46 ± 2.29 ng/ml) than diabetic boys (6.68 ± 0.91 ng/ml). Significant high level of serum IL-8 concentration (23 ± 11.92 pg/ml) was detected in IDDM children versus the control group (5.69 ± 1.67 pg/ml). On the other hand, serum nitrite values showed significant reduction in the IDDM children (430.78 ± 155.14 Μmol/l) compared to the control group (610.08 ± 192.82 Μmol/l). Correlation analysis showed positive correlation between leptin with age, (W/H)Z and fasting glucose level, furthermore, a positive correlation was established between IL-8 with (W/H)Z, hinting the adipose tissue as a site of its production and no association between NO and other relevant variables was detected. It could be concluded that

Mechanisms underlying differential expression of interleukin-8 in breast cancer cells

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Freund, Ariane; Jolivel, Valérie; Durand, Sébastien; Kersual, Nathalie; Chalbos, Dany; Chavey, Carine; Vignon, Françoise; Lazennec, Gwendal

2004-01-01

We have recently reported that Interleukin-8 (IL-8) expression was inversely correlated to estrogen-receptor (ER)-status and was overexpressed in invasive breast cancer cells. In the present study, we show that IL-8 overexpression in breast cancer cells involves a higher transcriptional activity of IL-8 gene promoter. Cloning of IL-8 promoter from MDA-MB-231 and MCF-7 cells expressing high and low levels of IL-8, respectively, shows the integrity of the promoter in both cell lines. Deletion and site-directed mutagenesis of the promoter demonstrate that NF-κB and AP-1 and to a lesser extent C/EBP binding sites play a crucial role in the control of IL-8 promoter activity in MDA-MB-231 cells. Knock-down of NF-κB and AP-1 activities by adenovirus-mediated expression of a NF-κB super-repressor and RNA interference, respectively, decreased IL-8 expression in MDA-MB-231 cells. On the contrary, restoration of Fra-1, Fra-2, c-Jun, p50, p65, C/EBPα and C/EBPβ expression levels in MCF-7 cells led to a promoter activity comparable to that observed in MDA-MB-231 cells. Our data constitute the first extensive study of IL-8 gene overexpression in breast cancer cells and suggest that the high expression of IL-8 in invasive cancer cells requires a complex cooperation between NF-κB, AP-1 and C/EBP transcription factors. PMID:15208657

Thromboxane A2 increases endothelial permeability through upregulation of interleukin-8

International Nuclear Information System (INIS)

Kim, Su-Ryun; Bae, Soo-Kyung; Park, Hyun-Joo; Kim, Mi-Kyoung; Kim, Koanhoi; Park, Shi-Young; Jang, Hye-Ock; Yun, Il; Kim, Yung-Jin; Yoo, Mi-Ae; Bae, Moon-Kyoung

2010-01-01

Thromboxane A 2 (TXA 2 ), a major prostanoid formed from prostaglandin H 2 by thromboxane synthase, is involved in the pathogenesis of a variety of vascular diseases. In this study, we report that TXA 2 mimetic U46619 significantly increases the endothelial permeability both in vitro and in vivo. U46619 enhanced the expression and secretion of interleukin-8 (IL-8), a major inducer of vascular permeability, in endothelial cells. Promoter analysis showed that the U46619-induced expression of IL-8 was mainly regulated by nuclear factor-κB (NF-κB). U46619 induced the activation of NF-κB through IκB kinase (IKK) activation, IκB phosphorylation and NF-κB nuclear translocation. Furthermore, the inhibition of IL-8 or blockade of the IL-8 receptor attenuated the U46619-induced endothelial cell permeability by modulating the cell-cell junctions. Overall, these results suggest that U46619 promotes vascular permeability through the production of IL-8 via NF-κB activation in endothelial cells.

The changes of interleukin-8 levels in gingival crevicular fluid in patients with periodontitis

International Nuclear Information System (INIS)

Zheng Jian; Li Hairu

2011-01-01

To explore the changes of interleukin-8 (IL-8) levels in gingival crevicular fluid (GCF) and their clinical significance in periodontitis patients. The IL-8 level in GCF from 67 teeth of 52 patients with adult periodontitis (AP), 37 teeth of 23 patients with rapidly progressive periodontitis (RPP) and 49 teeth of 31 normal controls were determined by RIA, and the clinical periodontoclasia indices of PD and AL were recorded. The results showed that the IL-8 levels in patients with AP and RPP were significantly higher than that of in health controls (P<0.01). The IL-8 was positively correlated to PD and AL. The results indicate that IL-8 may be one of the important cytokines in alveolar resorption of periodontoclasia. (authors)

Immunohistochemical expression of interleukin 8 in skin biopsies from patients with inflammatory acne vulgaris

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El Maged Rabee A

2007-01-01

Full Text Available Abstract Background This study was conducted to evaluate the immunohistochemical (IHC expression of interleukin 8 (IL-8 in skin biopsies of inflammatory acne vulgaris (IAV in an attempt to understand the disease pathogenesis. Materials and methods A total of 58 biopsies, 29 from lesional IAV and 29 normal non lesional sites were immunostained for IL-8. The intensity of staining was evaluated in the epidermis and dermis and was scored as mild, moderate and severe. The expression was correlated with the clinical grade, disease course and histological changes. Results IL-8 immunoreactivity was expressed in lesional IAV compared to non lesional skin biopsies (p Conclusion We were able to demonstrate altered immunoreactivity of IL-8 in IAV compared to normal skin. Targeted therapy to block IL-8 production may hold promise in limiting the deleterious effects of IL-8-mediated inflammatory response and angiogenesis.

Interleukin-6 and Interleukin-8 Levels Correlate With the Severity of Aplastic Anemia in Children.

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Gupta, Vineeta; Kumar, Sushil; Sonowal, Rimjhim; Singh, Surya K

2017-04-01

The aim of this study was to evaluate the levels of interleukin (IL)-6 and IL-8 in patients with aplastic anemia and its correlation with severity of the disease. IL-6 and IL-8 levels were measured in 40 patients with aplastic anemia in the age group of 4 to 14 years. A total of 40 healthy children served as controls. Quantitative estimation of IL-6 and IL-8 was performed using a solid-phase sandwich ELISA kit. Results were presented as IL-6 and IL-8 concentrations in pg/mL. Patients received immunosuppressive therapy per the British Committee for Standards in Haematology Guidelines 2009. Mean age of the patients was 9.78±2.74 years. IL-6 level of patients was elevated compared with controls (193.48±352.3 vs. 4.58±3.39; Paplastic anemia (724.33±519.42), followed by severe aplastic anemia (80.51±66.28 pg/mL), and non-severe aplastic anemia (6.01±1.89). Differences were statistically significant. A similar trend was also observed for IL-8 levels, where the levels were 41.02±24.23, 11.34±8.0, and 1.67±0.71 for very severe aplastic anemia, severe aplastic anemia, and non-severe aplastic anemia, respectively. The differences were again statistically significant. IL levels were also correlated with the treatment outcome. Responders had lower levels compared with nonresponders, but the difference was not statistically significant (186.36±322.45 vs. 198.74±368.10). Levels of ILs decreased in responders, but were not comparable with that of controls 6 months after therapy. High levels of IL-6 and IL-8 were observed in children with aplastic anemia. Increased levels showed correlation with disease severity and therefore appear to play an important role in aplastic anemia. However, levels had no significant correlation with the treatment outcome.

Serum levels of interleukin-6 and interleukin-8 as diagnostic markers of acute pyelonephritis in children

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Abolfazl Mahyar

2013-05-01

Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; Early diagnosis and treatment of acute pyelonephritis in children is of special importance in order to prevent serious complications. This study was conducted to determine the diagnostic value of serum interleukin (IL-6 and IL-8 in children with acute pyelonephritis. &lt;b&gt;Methods:&lt;/b&gt; Eighty seven patients between 1 month to 12 years old with urinary tract infection (UTI were divided into 2 groups based on the result of 99m-technetium dimercapto-succinic acid (DMSA renal scan: acute pyelonephritis (n=37 and lower UTI (n=50 groups. White blood cell (WBC count, neutrophil (Neutl count, erythrocyte sedimentation rate (ESR, C-reactive protein (CRP concentration, platelet count, and serum IL-6 and IL-8 concentrations of both groups were measured and compared . &lt;b&gt;Results:&lt;/b&gt; There was a significant difference between two groups regarding WBC count, Neutl count, ESR, and CRP concentration (P&lt;0.05. In addition, the difference between the two groups regarding serum IL-6 and IL-8 concentrations was not significant (IL-6, 60 and 35.4 pg/mL and IL-8, 404 and 617 pg/mL, respectively. The sensitivity and specificity of serum IL-6 and IL-8 for diagnosis of acute pyelonephritis were 73%, 42% and 78%, 32%, respectively. Sensitivity, specificity, negative and positive predictive values of serum IL-6 and IL-8 were less than those of acute phase serum reactants such as CRP. &lt;b&gt;Conclusion:&lt;/b&gt; This study showed that there was no significant difference between acute pyelonephritis and lower UTI groups regarding serum IL-6 and IL-8 levels. Therefore, despite confirming results of previous studies, it seems that IL-6 and IL-8 are not suitable markers for differentiating between acute pyelonephritis and lower UTI.

Comparison of IL-6, IL-8 Concentrations in H. pylori- and non-H. pylori-associated Gastritis

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Gontar Alamsyah Siregar

2014-12-01

Full Text Available BACKGROUND: Helicobacter pylori is a non-invasive microorganism causing intense gastric mucosal inflammatory and immune reaction. The gastric mucosal levels of the proinflammatory cytokines Interleukin 6 (IL-6 and IL-8 have been reported to be increased in H. pylori infection, but the serum levels in H. pylori infection is still controversial. The purpose of this study was to investigate the serum levels of IL-6 and IL-8 in H. pylori infection. METHODS: A cross sectional study was done on eighty consecutive gastritis patients admitted to endoscopy units at Adam Malik General Hospital and Permata Bunda Hospital, Medan, Indonesia from May-October 2014. Histopathology was performed for the diagnosis of gastritis. Rapid urease test for diagnosis of H. pylori infection. Serum samples were obtained to determine circulating IL-6 and IL-8. Univariate and bivariate analysis (independent t test were done. RESULTS: There were 41.25% patients infected with H. pylori. Circulatory IL-6 levels were significantly higher in H. pylori-infected patients compared to H. pylori negative, but there were no differences between serum levels of IL-8 in H. pylori positive and negative patients. CONCLUSIONS: The immune response to H. pylori promotes systemic inflammation, which was reflected in an increased level of serum IL-6. Serum levels of IL-8 were not significantly different between H. pylori positive and negative. KEYWORDS: Helicobacter pylori, gastritis, IL-6, IL-8, cytokine.

Melatonin suppresses acrolein-induced IL-8 production in human pulmonary fibroblasts.

Science.gov (United States)

Kim, Gun-Dong; Lee, Seung Eun; Kim, Tae-Ho; Jin, Young-Ho; Park, Yong Seek; Park, Cheung-Seog

2012-04-01

Cigarette smoke (CS) causes harmful alterations in the lungs and airway structures and functions that characterize chronic obstructive pulmonary disease (COPD). In addition to COPD, active cigarette smoking causes other respiratory diseases and diminishes health status. Furthermore, recent studies show that, α, β-unsaturated aldehyde acrolein in CS induces the production of interleukin (IL)-8, which is known to be related to bronchitis, rhinitis, pulmonary fibrosis, and asthma. In addition, lung and pulmonary fibroblasts secrete IL-8, which has a chemotactic effect on leukocytes, and which in turn, play a critical role in lung inflammation. On the other hand, melatonin regulates circadian rhythm homeostasis in humans and has many other effects, which include antioxidant and anti-inflammatory effects, as demonstrated by the reduced expressions of iNOS, IL-1β, and IL-6 and increased glutathione (GSH) and superoxide dismutase activities. In this study, we investigated whether melatonin suppresses acrolein-induced IL-8 secretion in human pulmonary fibroblasts (HPFs). It was found that acrolein-induced IL-8 production was accompanied by increased levels of phosphorylation of Akt and extracellular signal-regulated kinases (ERK1/2) in HPFs, and that melatonin suppressed IL-8 production in HPFs. These results suggest that melatonin suppresses acrolein-induced IL-8 production via ERK1/2 and phosphatidylinositol 3-kinase (PI3K)/Akt signal inhibition in HPFs. © 2011 John Wiley & Sons A/S.

Carbon monoxide releasing molecule-2 ameliorates IL-1β-induced IL-8 in human gastric cancer cells

International Nuclear Information System (INIS)

Lian, Sen; Xia, Yong; Ung, Trong Thuan; Khoi, Pham Ngoc; Yoon, Hyun Joong; Kim, Nam Ho; Kim, Kyung Keun; Jung, Young Do

2016-01-01

Carbon monoxide (CO), a byproduct of heme oxygenase (HO), presents antioxidant, anti-inflammatory, and anti-tumor properties. Accumulating evidence supports that interleukin (IL)-8 contribute to the vascularity of human gastric cancer. However, the inhibition of IL-8 expression by CO is yet to be elucidated. Here, we utilized CO releasing molecule-2 (CORM-2) to investigate the effect of CO on IL-1β-induced IL-8 expression and the underlying molecular mechanisms in human gastric cancer AGS cells. CORM-2 dose-dependently suppressed IL-1β-induced IL-8 mRNA and protein expression as well as IL-8 promoter activity. IL-1β induced the translocation of p47 phox to activate reactive oxygen species (ROS)-producing NADPH oxidase (NOX). Moreover, IL-1β activated MAPKs (Erk1/2, JNK1/2, and p38 MAPK) and promoted nuclear factor (NF)-kB and activator protein (AP)-1 binding activities. Pharmacological inhibition and mutagenesis studies indicated that NOX, ROS, Erk1/2, and p38 MAPK are involved in IL-1β-induced IL-8 expression. Transient transfection of deletion mutant constructs of the IL-8 promoter in cells suggested that NF-kB and AP-1 are critical for IL-1β-induced IL-8 transcription. NOX-derived ROS and MAPKs (Erk1/2 and p38 MAPK) functioned as upstream activators of NF-κB and AP-1, respectively. CORM-2 pretreatment significantly mitigated IL-1β-induced activation of ROS/NF-kB and Erk1/2/AP-1 cascades, blocking IL-8 expression and thus significantly reducing endothelial cell proliferation in the tumor microenvironment.

Intraperitoneal interleukin-8 and neutrophil influx in the initial phase of a CAPD peritonitis

NARCIS (Netherlands)

Betjes, M. G.; Visser, C. E.; Zemel, D.; Tuk, C. W.; Struijk, D. G.; Krediet, R. T.; Arisz, L.; Beelen, R. H.

1996-01-01

OBJECTIVE: To investigate whether or not a change in dialysate interleukin-8 (IL-8) concentration precedes the onset of clinically overt peritonitis and is significant in the recruitment of granulocytes during continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. DESIGN: CAPD

Ozone Enhances Diesel Exhaust Particles (DEP-Induced Interleukin-8 (IL-8 Gene Expression in Human Airway Epithelial Cells through Activation of Nuclear Factors- κB (NF-κB and IL-6 (NF-IL6

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James Kelley

2005-12-01

Full Text Available Ozone, a highly reactive oxidant gas is a major component of photochemical smog. As an inhaled toxicant, ozone induces its adverse effects mainly on the lung. Inhalation of particulate matter has been reported to cause airway inflammation in humans and animals. Furthermore, epidemiological evidence has indicated that exposure to particulate matter (PM2.5-10, including diesel exhaust particles (DEP has been correlated with increased acute and chronic respiratory morbidity and exacerbation of asthma. Previously, exposure to ozone or particulate matter and their effect on the lung have been addressed as separate environmental problems. Ozone and particulate matter may be chemically coupled in the ambient air. In the present study we determined whether ozone exposure enhances DEP effect on interleukin-8 (IL-8 gene expression in human airway epithelial cells. We report that ozone exposure (0.5 ppm x 1 hr significantly increased DEP-induced IL-8 gene expression in A549 cells (117 ± 19 pg/ml, n = 6, p < 0.05 as compared to cultures treated with DEP (100 μg/ml x 4 hr alone (31 ± 3 pg/ml, n = 6, or cultures exposed to purified air (24 ± 6 pg/ml, n = 6. The increased DEP-induced IL-8 gene expression following ozone exposure was attributed to ozone-induced increase in the activity of the transcription factors NF-κB and NF-IL6. The results of the present study indicate that ozone exposure enhances the toxicity of DEP in human airway epithelial cells by augmenting IL-8 gene expression, a potent chemoattractant of neutrophils in the lung.

Genome-wide association study of genetic variants in LPS-stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-α cytokine response in a Danish Cohort

DEFF Research Database (Denmark)

Larsen, Margit Hørup; Albrechtsen, Anders; Thørner, Lise Wegner

2013-01-01

Cytokine response plays a vital role in various human lipopolysaccharide (LPS) infectious and inflammatory diseases. This study aimed to find genetic variants that might affect the levels of LPS-induced interleukin (IL)-6, IL-8, IL-10, IL-1ra and tumor necrosis factor (TNF)-α cytokine production....

Korelasi Jumlah Streptococcus mutans (S. mutans dan Level Ekspresi Interlukin 8 (IL-8 pada Severe Early Childhood Caries

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Muhammad Luthfi

2015-12-01

Full Text Available Karies gigi pada anak usia dini merupakan masalah kesehatan yang sangat serius karena merupakan penyakit infeksi kronis yang menular. Dalam beberapa tahun terakhir pandangan tentang neutrofil telah berubah secara dramatis. Neutrofil tidak hanya berperan sebagai pembunuh mikroba melalui proses fagositosis, pelepasan reactive oxigen species (ROS dan peptida antimikrobialnya tetapi neutrofil turut mengatur aktifasi respon imun. Interleukin-8 (IL-8 berfungsi sebagai aktivator kuat dan kemoatraktan neutrofil oleh karena itu IL-8 merupakan mediator kunci dalam migrasi neutrofil ke lokasi peradangan dan infeksi. Untuk menganalisis hubungan dari jumlah S. mutans dan ekspresi IL-8 neutrofil saliva pada anak usia dini bebas karies dan severe early childhood caries (S-ECC. Perlakuan dilakukan pada dua kelompok yaitu isolasi dan menghitung jumlah S. mutans pada sampel saliva dan sampel hasil kumur dengan NaCl 1,5% yang diisolasi neutrofilnya kemudian dianalisis ekspresi IL-8 menggunakan flow cytometry dari 20 anak bebas karies dan 20 anak severe early childhood caries. Hasil nilai rata-rata diketahui bahwa jumlah S. mutans anak usia dini bebas karies lebih rendah (513.500,00±185.565,28 CFU/ml dibandingkan dengan S-ECC (977.000,00±222.500,15 CFU/ml, sedangkan ekspresi IL-8 neutrofil saliva anak usia dini bebas karies lebih tinggi (3,31±0,50 dibandingkan dengan S-ECC (2,95+0,56. Penurunan ekspresi IL-8 neutrofil saliva kemungkinan sebagai penyebab meningkatnya jumlah S. mutans pada S-ECC. Correlation of Streptococcus mutans (S. mutans Level and Interleukin 8 (IL-8 Expressions of Salivary Neutrophils in Severe Early Childhood Caries. Early childhood caries is a very serious health problem because it is a chronic infectious disease that is contagious. Dental caries begins after the primary teeth grow and develop on the tooth surface very quickly and progressively. In recent years the views of neutrophils have changed dramatically. Neutrophils

Three-dimensional structure of interleukin 8 in solution

International Nuclear Information System (INIS)

Clore, G.M.; Appella, E.; Gronenborn, A.M.; Yamada, Masaki; Matsushima, Kouji

1990-01-01

The solution structure of the interleukin 8 (IL-8) dimer has been solved by nuclear magnetic resonance (NMR) spectroscopy and hybrid distance geometry-dynamical simulated annealing calculations. The structure determination is based on a total of 1,880 experimental distance restraints (of which 82 are intersubunit) and 362 torsion angle restraints (comprising φ, ψ, and χ 1 torsion angles). A total of 30 simulated annealing structures were calculated, and the atomic rms distribution about the mean coordinate positions (excluding residues 1-5 of each subunit) is 0.41 ± 0.08 angstrom for the backbone atoms and 0.90 ± 0.08 angstrom for all atoms. The three-dimensional solution structure of the IL-8 dimer reveals a structural motif in which two symmetry-related antiparallel α-helices, approximately 24 angstrom long and separated by about 14 angstrom, lie on top of six-stranded antiparallel β-sheet platform derived from two three-stranded Greek keys, one from each monomer unit. The general architecture is similar to that of the α1/α2 domains of the human class I histocompatibility antigen HLA-A2. It is suggested that the two α-helices form the binding site for the cellular receptor and that the specificity of IL-8, as well as that of a number of related proteins involved in cell-specific chemotaxis, mediation of cell growth, and the inflammatory response, is achieved by the distinct distribution of charged and polar residues at the surface of the helices

Three-dimensional structure of interleukin 8 in solution.

Science.gov (United States)

Clore, G M; Appella, E; Yamada, M; Matsushima, K; Gronenborn, A M

1990-02-20

The solution structure of the interleukin 8 (IL-8) dimer has been solved by nuclear magnetic resonance (NMR) spectroscopy and hybrid distance geometry-dynamical simulated annealing calculations. The structure determination is based on a total of 1880 experimental distance restraints (of which 82 are intersubunit) and 362 torsion angle restraints (comprising phi, psi, and chi 1 torsion angles). A total of 30 simulated annealing structures were calculated, and the atomic rms distribution about the mean coordinate positions (excluding residues 1-5 of each subunit) is 0.41 +/- 0.08 A for the backbone atoms and 0.90 +/- 0.08 A for all atoms. The three-dimensional solution structure of the IL-8 dimer reveals a structural motif in which two symmetry-related antiparallel alpha-helices, approximately 24 A long and separated by about 14 A, lie on top of a six-stranded antiparallel beta-sheet platform derived from two three-stranded Greek keys, one from each monomer unit. The general architecture is similar to that of the alpha 1/alpha 2 domains of the human class I histocompatibility antigen HLA-A2. It is suggested that the two alpha-helices form the binding site for the cellular receptor and that the specificity of IL-8, as well as that of a number of related proteins involved in cell-specific chemotaxis, mediation of cell growth, and the inflammatory response, is achieved by the distinct distribution of charged and polar residues at the surface of the helices.

IFN-gamma Impairs Release of IL-8 by IL-1beta-stimulated A549 Lung Carcinoma Cells

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Pfeilschifter Josef

2008-09-01

Full Text Available Abstract Background Production of interferon (IFN-γ is key to efficient anti-tumor immunity. The present study was set out to investigate effects of IFNγ on the release of the potent pro-angiogenic mediator IL-8 by human A549 lung carcinoma cells. Methods A549 cells were cultured and stimulated with interleukin (IL-1β alone or in combination with IFNγ. IL-8 production by these cells was analyzed with enzyme linked immuno sorbent assay (ELISA. mRNA-expression was analyzed by real-time PCR and RNase protection assay (RPA, respectively. Expression of inhibitor-κ Bα, cellular IL-8, and cyclooxygenase-2 was analyzed by Western blot analysis. Results Here we demonstrate that IFNγ efficiently reduced IL-8 secretion under the influence of IL-1β. Surprisingly, real-time PCR analysis and RPA revealed that the inhibitory effect of IFNγ on IL-8 was not associated with significant changes in mRNA levels. These observations concurred with lack of a modulatory activity of IFNγ on IL-1β-induced NF-κB activation as assessed by cellular IκB levels. Moreover, analysis of intracellular IL-8 suggests that IFNγ modulated IL-8 secretion by action on the posttranslational level. In contrast to IL-8, IL-1β-induced cyclooxygenase-2 expression and release of IL-6 were not affected by IFNγ indicating that modulation of IL-1β action by this cytokine displays specificity. Conclusion Data presented herein agree with an angiostatic role of IFNγ as seen in rodent models of solid tumors and suggest that increasing T helper type 1 (Th1-like functions in lung cancer patients e.g. by local delivery of IFNγ may mediate therapeutic benefit via mechanisms that potentially include modulation of pro-angiogenic IL-8.

Grain dust induces IL-8 production from bronchial epithelial cells: effect on neutrophil recruitment.

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Park, H S; Suh, J H; Kim, S S; Kwon, O J

2000-06-01

There have been several investigations suggesting an involvement of activated neutrophils in the development of grain dust (GD)-induced occupational asthma. Interleukin-8 in the sputa from GD-induced asthmatic patients increased significantly after the exposure to GD. To confirm IL-8 production from bronchial epithelial cells when exposed to GD, and to evaluate the role of IL-8 on neutrophil recruitment. We cultured Beas-2B, a bronchial epithelial cell line. To observe GD-induced responses, four different concentrations ranging from 1 to 200 microg/mL of GD were incubated for 24 hours and compared with those without incubation of GD. To evaluate the effect of pro-inflammatory cytokines on IL-8 production and neutrophil chemotaxis, epithelial cells were incubated with peripheral blood mononuclear cell (PBMC) culture supernatant derived from subjects with GD-induced asthma exposed to 10 microg/mL of GD, and then compared with those without addition of PBMC supernatant. The level of released IL-8 in the supernatant was measured by enzyme-linked immunosorbent assay. Neutrophil chemotactic activity of the culture supernatant was determined by modified Boyden chamber method. Interleukin-8 production and neutrophil chemotactic activity from bronchial epithelial cells significantly increased with additions of GD in a dose-dependent manner (P < .05, respectively), and were significantly augmented with additions of PBMC supernatant (P < .05, respectively) at each concentration. Close correlation was noted between neutrophil chemotactic activity and IL-8 level (r = 0.87, P < .05). Compared with the untreated sample, pre-treatment of anti-IL-8 antibody induced a significant suppression (up to 67.2%) of neutrophil chemotactic activity in a dose-dependent manner. These results suggest that IL-8 produced from bronchial epithelial cells may be a major cytokine, which induces neutrophil migration into the airways when exposed to GD.

A computational study of the chemokine receptor CXCR1 bound with interleukin-8

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Wang, Yang; Severin Lupala, Cecylia; Wang, Ting; Li, Xuanxuan; Yun, Ji-Hye; Park, Jae-hyun; Jin, Zeyu; Lee, Weontae; Tan, Leihan; Liu, Haiguang

2018-03-01

CXCR1 is a G-protein coupled receptor, transducing signals from chemokines, in particular the interleukin-8 (IL8) molecules. This study combines homology modeling and molecular dynamics simulation methods to study the structure of CXCR1-IL8 complex. By using CXCR4-vMIP-II crystallography structure as the homologous template, CXCR1-IL8 complex structure was constructed, and then refined using all-atom molecular dynamics simulations. Through extensive simulations, CXCR1-IL8 binding poses were investigated in detail. Furthermore, the role of the N-terminal of CXCR1 receptor was studied by comparing four complex models differing in the N-terminal sequences. The results indicate that the receptor N-terminal affects the binding of IL8 significantly. With a shorter N-terminal domain, the binding of IL8 to CXCR1 becomes unstable. The homology modeling and simulations also reveal the key receptor-ligand residues involved in the electrostatic interactions known to be vital for complex formation. Project supported by the National Natural Science Foundation of China (Grant Nos. 11575021, U1530401, and U1430237) and the National Research Foundation of Korea (Grant Nos. NRF-2017R1A2B2008483 and NRF-2016R1A6A3A04010213).

Glutamine deprivation induces interleukin-8 expression in ataxia telangiectasia fibroblasts.

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Kim, Min-Hyun; Kim, Aryung; Yu, Ji Hoon; Lim, Joo Weon; Kim, Hyeyoung

2014-05-01

To investigate whether glutamine deprivation induces expression of inflammatory cytokine interleukin-8 (IL-8) by determining NF-κB activity and levels of oxidative indices (ROS, reactive oxygen species; hydrogen peroxide; GSH, glutathione) in fibroblasts isolated from patients with ataxia telangiectasia (A-T). We used A-T fibroblasts stably transfected with empty vector (Mock) or with human full-length ataxia telangiectasia mutated (ATM) cDNA (YZ5) and mouse embryonic fibroblasts (MEFs) transiently transfected with ATM small interfering RNA (siRNA) or with non-specific control siRNA. The cells were cultured with or without glutamine or GSH. ROS levels were determined using a fluorescence reader and confocal microscopy. IL-8 or murine IL-8 homolog, keratinocyte chemoattractant (KC), and hydrogen peroxide levels in the medium were determined by enzyme-linked immunosorbent assay and colorimetric assay. GSH level was assessed by enzymatic assay, while IL-8 (KC) mRNA level was measured by reverse transcription-polymerase chain reaction (RT-PCR) and/or quantitative real-time PCR. NF-κB DNA-binding activity was determined by electrophoretic mobility shift assay. Catalase activity and ATM protein levels were determined by O2 generation and Western blotting. While glutamine deprivation induced IL-8 expression and increased NF-κB DNA-binding activity in Mock cells, both processes were decreased by treatment of cells with glutamine or GSH or both glutamine and GSH. Glutamine deprivation had no effect on IL-8 expression or NF-κB DNA-binding activity in YZ5 cells. Glutamine-deprived Mock cells had higher oxidative stress indices (increases in ROS and hydrogen peroxide, reduction in GSH) than glutamine-deprived YZ5 cells. In Mock cells, glutamine deprivation-induced oxidative stress indices were suppressed by treatment with glutamine or GSH or both glutamine and GSH. GSH levels and catalase activity were lower in Mock cells than YZ5 cells. MEFs transfected with ATM siRNA and

[Expressions of interleukin-17 and interleukin-8 in the prostatic tissue of the patients with BPH or BPH with inflammation].

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Gao, Rui; Liu, Qi-Xiang; Zhou, Hui-Liang; Cao, Lin-Sheng; Jiang, Tao; Tang, Song-Xi; Ding, Yi-Lang

2017-08-01

To investigate the expressions of interleukin-17 (IL-17) and interleukin-8 (IL-8) in benign prostatic hyperplasia (BPH) and BPH complicated with histological inflammation and their significance. According to the results of HE staining, we divided 60 cases of BPH treated by transurethral resection of the prostate (TURP) into a BPH group (n = 23) and a BPH with inflammation group (n = 37). We analyzed the clinical data of the patients and determined the mRNA and protein expressions of IL-17 and IL-8 by immunohistochemistry, real-time fluorescence quantitative PCR, and Western blot, respectively. Compared with the BPH patients complicated with inflammation, the BPH group showed significantly lower International Prostate Symptom Score (IPSS) (29.1 ± 6.2 vs 21.6 ± 3.7), quality of life score (QoL) (5.4 ± 1.3 vs 4.4 ± 1.6), postvoid residual urine volume (RUV) (［198.6 ± 15.5］ vs ［98.2 ± 19.3］ ml), prostate volume (［69.2 ± 24.1］ vs ［49.8 ± 16.5］ ml), PSA level (［7.4 ± 1.9］ vs ［2.8 ± 0.8］ μg/L) and serum c-reactive protein content (CRP) (［5.1±2.0］ vs ［1.5±0.6］ mg/L), but a higher maximum urine flow rate (Qmax) (［4.7 ± 2.1］ vs ［8.2 ± 1.8］ ml/s) (all PBPH patients with inflammation, which may play a significant role in the development and progression of BPH.

Elevated interleukin-8 enhances prefrontal synaptic transmission in mice with persistent inflammatory pain

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Cui Guang-bin

2012-02-01

Full Text Available Abstract Background Interleukin-8 (IL-8 is known for its roles in inflammation and plays critical roles in the development of pain. Its expression increases in the brain after peripheral inflammation. Prefrontal cortex, including the anterior cingulate cortex (ACC, is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission, however, little is known about the expression of IL-8 and its role in the enhanced ACC synaptic transmission in animals with persistent inflammatory pain. Findings In the present study, we examined IL-8 expression in the ACC, somatosensory cortex (SSC, and the dorsal horn of lumbar spinal cord following hind-paw administration of complete Freund's adjuvant (CFA in mice and its effects on the ACC synaptic transmission. Quantification of IL-8 at protein level (by ELISA revealed enhanced expression in the ACC and spinal cord during the chronic phases of CFA-induced peripheral inflammation. In vitro whole-cell patch-clamp recordings revealed that IL-8 significantly enhanced synaptic transmission through increased probability of neurotransmitter release in the ACC slice. ACC local infusion of repertaxin, a non-competitive allosteric blocker of IL-8 receptors, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in mice. Conclusions Our findings suggest that up-regulation of IL-8 in the ACC partly attributable to the enhanced prefrontal synaptic transmission in the mice with persistent inflammatory pain.

CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis

International Nuclear Information System (INIS)

Wang, Hongkai; Zhuo, Yunyun; Hu, Xu; Shen, Weiwei; Zhang, Ying; Chu, Tongwei

2015-01-01

Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients. - Highlights: • Bone loss frequently results from lung cancer metastasis. • Cluster of differentiation (CD)147 was depleted in A549 lung adenocarcinoma cells. • RAW 264.7 cell osteoclastogenesis was blocked by medium from CD147-deficient cells. • Interleukin (IL)-8 level was reduced in the conditioned medium. • Osteoclastogenesis induced by lung tumor cells requires CD147-mediated IL-8 release

CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis

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Wang, Hongkai; Zhuo, Yunyun; Hu, Xu; Shen, Weiwei; Zhang, Ying; Chu, Tongwei, E-mail: chtw@sina.com

2015-03-06

Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients. - Highlights: • Bone loss frequently results from lung cancer metastasis. • Cluster of differentiation (CD)147 was depleted in A549 lung adenocarcinoma cells. • RAW 264.7 cell osteoclastogenesis was blocked by medium from CD147-deficient cells. • Interleukin (IL)-8 level was reduced in the conditioned medium. • Osteoclastogenesis induced by lung tumor cells requires CD147-mediated IL-8 release.

Differential effects of multiplicity of infection on Helicobacter pylori-induced signaling pathways and interleukin-8 gene transcription.

Science.gov (United States)

Ritter, Birgit; Kilian, Petra; Reboll, Marc Rene; Resch, Klaus; DiStefano, Johanna Kay; Frank, Ronald; Beil, Winfried; Nourbakhsh, Mahtab

2011-02-01

Interleukin-8 (IL-8) plays a central role in the pathogenesis of Helicobacter pylori infection. We used four different H. pylori strains isolated from patients with gastritis or duodenal ulcer disease to examine their differential effects on signaling pathways and IL-8 gene response in gastric epithelial cells. IL-8 mRNA level is elevated in response to high (100) multiplicity of infection (MOI) independent of cagA, vacA, and dupA gene characteristics. By lower MOIs (1 or 10), only cagA ( + ) strains significantly induce IL-8 gene expression. This is based on differential regulation of IL-8 promoter activity. Analysis of intracellular signaling pathways indicates that H. pylori clinical isolates induce IL-8 gene transcription through NF-κB p65, but by a MOI-dependent differential activation of MAPK pathways. Thus, the major virulence factors of H. pylori CagA, VacA, and DupA might play a minor role in the level of IL-8 gene response to a high bacterial load.

Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells

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Poghosyan, Anna, E-mail: pannagos@yahoo.com; Patel, Jamie K.; Clifford, Rachel L.; Knox, Alan J., E-mail: alan.knox@nottingham.ac.uk

2016-08-05

Airway epithelial cells in cystic fibrosis (CF) overexpress Interleukin 8 (CXCL8) through poorly defined mechanisms. CXCL8 transcription is dependent on coordinated binding of CCAAT/enhancer binding protein (C/EBP)β, nuclear factor (NF)-κB, and activator protein (AP)-1 to the promoter. Here we show abnormal epigenetic regulation is responsible for CXCL8 overexpression in CF cells. Under basal conditions CF cells had increased bromodomain (Brd)3 and Brd4 recruitment and enhanced NF-κB and C/EBPβ binding to the CXCL8 promoter compared to non-CF cells due to trimethylation of histone H3 at lysine 4 (H3K4me3) and DNA hypomethylation at CpG6. IL-1β increased NF-κB, C/EBPβ and Brd4 binding. Furthermore, inhibitors of bromodomain and extra-terminal domain family (BET) proteins reduced CXCL8 production in CF cells suggesting a therapeutic target for the BET pathway. -- Highlights: •A regulatory mechanism of CXCL8 transcriptional control in CF airways is proposed. •There was an increased binding of NF-κB and C/EBPβ transcription factors. •There was enhanced recruitment of BET proteins to the CXCL8 promoter. •Epigenetic modifications are responsible for the aberrant CXCL8 transcription.

Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells

International Nuclear Information System (INIS)

Poghosyan, Anna; Patel, Jamie K.; Clifford, Rachel L.; Knox, Alan J.

2016-01-01

Airway epithelial cells in cystic fibrosis (CF) overexpress Interleukin 8 (CXCL8) through poorly defined mechanisms. CXCL8 transcription is dependent on coordinated binding of CCAAT/enhancer binding protein (C/EBP)β, nuclear factor (NF)-κB, and activator protein (AP)-1 to the promoter. Here we show abnormal epigenetic regulation is responsible for CXCL8 overexpression in CF cells. Under basal conditions CF cells had increased bromodomain (Brd)3 and Brd4 recruitment and enhanced NF-κB and C/EBPβ binding to the CXCL8 promoter compared to non-CF cells due to trimethylation of histone H3 at lysine 4 (H3K4me3) and DNA hypomethylation at CpG6. IL-1β increased NF-κB, C/EBPβ and Brd4 binding. Furthermore, inhibitors of bromodomain and extra-terminal domain family (BET) proteins reduced CXCL8 production in CF cells suggesting a therapeutic target for the BET pathway. -- Highlights: •A regulatory mechanism of CXCL8 transcriptional control in CF airways is proposed. •There was an increased binding of NF-κB and C/EBPβ transcription factors. •There was enhanced recruitment of BET proteins to the CXCL8 promoter. •Epigenetic modifications are responsible for the aberrant CXCL8 transcription.

Interleukin 8 as a vaso-occlusive marker in Brazilian patients with sickle cell disease.

Science.gov (United States)

Gonçalves, M S; Queiroz, I L; Cardoso, S A; Zanetti, A; Strapazoni, A C; Adorno, E; Albuquerque, A; Sant'Ana, A; dos Reis, M G; Barral, A; Barral Netto, M

2001-10-01

Sickle cell disease has a worldwide distribution and is a public health problem in Brazil. Although vaso-occlusive crisis (VOC) is one of the most important clinical features of the disease, there are still several steps of its pathogenesis which are unknown. The increase of the chemotactic factor interleukin 8 (IL-8) has been reported to be involved in sickle cell disease crisis, but this has not been demonstrated conclusively. In the present study we analyzed serum IL-8 levels by ELISA and hematological parameters and hemoglobin patterns by standard techniques in 23 (21 SS and 2 SC) Brazilian patients with sickle cell syndromes during VOC caused by different inducing factors, 22 (21 SS and 1 SC) sickle cell patients out of crisis, and 11 healthy controls. Increased IL-8 levels were observed in 19 of 23 VOC patients (79.2%), 3 of them with more than 1,000 pg/ml. Seventeen of 22 (77.3%) non-crisis patients showed low IL-8 levels (less than 15 pg/ml). Healthy controls had low IL-8 levels. A significant difference in serum IL-8 levels was observed between crisis and non-crisis sickle cell patients (Pcrisis-inducing factor. We conclude that in the studied population, IL-8 concentration may be a useful VOC marker, although the mechanism of the pathogenic process of sickle cell VOC syndromes remains unclear.

Interleukin-8 for diagnosis of neonatal sepsis: a meta-analysis.

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Min Zhou

Full Text Available Neonatal sepsis (NS is a life-threatening disorder and an important cause of morbidity and mortality in neonates. Previous studies showed that interleukin 8 (IL-8 may effectively and rapidly diagnose NS.We conducted the systematic review and meta-analysis to investigate the diagnostic value of the IL-8 in NS.The literature was searched in PUBMED, EMBASE, Cochrane Library, CNKI, VIP and other Chinese Medical Databases during October 1998 to January 2014 using set search criteria. Each included study was evaluated by quality assessment of diagnostic accuracy studies tool. Two investigators independently extracted the data and study characteristics, and disagreements, if any, were resolved by consensus. Meta-disc software was used to calculate the pooled sensitivity, specificity and summary diagnostic odds ratio (SDOR, I² or Cochrane Q to test heterogeneity, and meta-regression to investigate the source of heterogeneity. Funnel plots were used to test the potential presence of publication bias. False-positive report probability (FPRP was calculated to confirm the significance of the results.Eight studies (548 neonates were included in this meta-analysis. The pooled sensitivity and specificity of IL-8 were 0.78 and 0.84, respectively, which had moderate accuracy in the diagnosis of NS. The pooled diagnostic odds ratio (DOR and area under curve (AUC was 21.64 and 0.8908 (Q*=0.8215, respectively. The diagnostic threshold analysis showed that there was no threshold effect. The meta-regression analysis showed the cut-off, QUADAS and onset time have no effect on the heterogeneity. The funnel plots showed the existence of publication bias.Meta-analysis showed IL-8 had a moderate accuracy (AUC=0.8908 for the diagnosis of NS. IL-8 is a helpful biomarker for early diagnosis of NS. However, we should combine the results with clinical symptoms and signs, laboratory and microbial results.

The effects of interleukin-8 on airway smooth muscle contraction in cystic fibrosis

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Safka Katherine

2008-12-01

Full Text Available Abstract Background Many cystic fibrosis (CF patients display airway hyperresponsiveness and have symptoms of asthma such as cough, wheezing and reversible airway obstruction. Chronic airway bacterial colonization, associated with neutrophilic inflammation and high levels of interleukin-8 (IL-8 is also a common occurrence in these patients. The aim of this work was to determine the responsiveness of airway smooth muscle to IL-8 in CF patients compared to non-CF individuals. Methods Experiments were conducted on cultured ASM cells harvested from subjects with and without CF (control subjects. Cells from the 2nd to 5th passage were studied. Expression of the IL-8 receptors CXCR1 and CXCR2 was assessed by flow cytometry. The cell response to IL-8 was determined by measuring intracellular calcium concentration ([Ca2+]i, cell contraction, migration and proliferation. Results The IL-8 receptors CXCR1 and CXCR2 were expressed in both non-CF and CF ASM cells to a comparable extent. IL-8 (100 nM induced a peak Ca2+ release that was higher in control than in CF cells: 228 ± 7 versus 198 ± 10 nM (p 20 in CF than in control cells. In addition, MLC20 expression was also increased in CF cells. Exposure to IL-8 induced migration and proliferation of both groups of ASM cells but was not different between CF and non-CF cells. Conclusion ASM cells of CF patients are more contractile to IL-8 than non-CF ASM cells. This enhanced contractility may be due to an increase in the amount of contractile protein MLC20. Higher expression of MLC20 by CF cells could contribute to airway hyperresponsiveness to IL-8 in CF patients.

Knockdown of IL-8 Provoked Premature Senescence of Placenta-Derived Mesenchymal Stem Cells.

Science.gov (United States)

Li, Juan-Juan; Ma, Feng-Xia; Wang, You-Wei; Chen, Fang; Lu, Shi-Hong; Chi, Ying; Du, Wen-Jing; Song, Bao-Quan; Hu, Liang-Ding; Chen, Hu; Han, Zhong-Chao

2017-06-15

Mesenchymal stem cells (MSCs) have shown promise for use in cell therapy, and due to their tumor tropism can serve as vehicles for delivering therapeutic agents to tumor sites. Because interleukin-8 (IL-8) is known to mediate the protumor effect of MSCs, elimination of IL-8 secretion by MSCs may enhance their safety for use in cancer gene therapy. However, little is known concerning the effect of endogenously secreted IL-8 on MSCs. We performed studies using placenta-derived MSCs (PMSCs) to determine whether knockdown of IL-8 would influence their biological activity. We first verified that IL-8 and its membrane receptor CXCR2, but not CXCR1, were highly expressed in PMSCs. We then employed lentivirus-mediated small hairpin RNA interference to generate stable IL-8-silenced PMSCs, which displayed a variety of characteristic senescent phenotypes. We observed that at day 9 post-transfection, IL-8-silenced PMSCs had become larger and displayed a more flattened appearance when compared with their controls. Moreover, their proliferation, colony forming unit-fibroblast formation, adipogenic and osteogenic differentiation, and immunosuppressive potentials were significantly impaired. Enhanced senescence-associated β-galactosidase (SA-β-gal) activity and specific global gene expression profiles confirmed that IL-8 silencing evoked the senescence process in PMSCs. Increased levels of p-Akt and decreased levels of FOXO3a protein expression suggested that reactive oxygen species played a role in the initiation and maintenance of senescence in IL-8-silenced PMSCs. Notably, the majority of CXCR2 ligands were downregulated in presenescent IL-8-silenced PMSCs but upregulated in senescent cells, indicating an antagonistic pleiotropy of the IL-8/CXCR2 signaling pathway in PMSCs. This effect may promote the proliferation of young cells and accelerate senescence of old cells.

Streptococcus gordonii lipoproteins induce IL-8 in human periodontal ligament cells.

Science.gov (United States)

Kim, A Reum; Ahn, Ki Bum; Kim, Hyun Young; Seo, Ho Seong; Kum, Kee-Yeon; Yun, Cheol-Heui; Han, Seung Hyun

2017-11-01

Streptococcus gordonii, a Gram-positive oral bacterium, is a life-threatening pathogen that causes infective endocarditis. It is frequently isolated from the periapical lesions of patients with apical periodontitis and has thus been implicated in inflammatory responses. However, little is known about the virulence factors of S. gordonii responsible for the induction of inflammatory responses in the periapical areas. Here, we investigated the role of S. gordonii cell wall-associated virulence factors on interleukin (IL)-8 induction in human periodontal ligament (PDL) cells using ethanol-inactivated wild-type S. gordonii, a lipoteichoic acid (LTA)-deficient mutant (ΔltaS), and a lipoprotein-deficient mutant (Δlgt). Wild-type S. gordonii induced IL-8 expression at both the protein and mRNA levels in human PDL cells in a dose- and time-dependent manner. A transient transfection and reporter gene assay demonstrated that wild-type S. gordonii activated Toll-like receptor 2 (TLR2). Additionally, IL-8 production induced by wild-type S. gordonii was substantially inhibited by anti-TLR2-neutralizing antibodies. Both wild-type S. gordonii and the ΔltaS mutant induced IL-8 production; however, this response was not observed when cells were stimulated with the Δlgt mutant. Interestingly, lipoproteins purified from S. gordonii induced IL-8 production, whereas purified LTA did not. In addition, purified lipoproteins stimulated TLR2 more potently than LTA. Furthermore, S. gordonii-induced IL-8 expression was specifically inhibited by blocking p38 kinase, while lipoprotein-induced IL-8 expression was inhibited by blocking p38 kinase, ERK, or JNK. Of particular note, exogenous addition of purified S. gordonii lipoproteins enhanced Δlgt-induced IL-8 production in human PDL cells to an extent similar to that induced by the wild-type strain. Collectively, these results suggest that lipoproteins are an important component of S. gordonii for the induction of IL-8 production in human

ARSENITE ACTIVATES KB-DEPENDENT IL-8 GENE EXPRESSION IN AIRWAY EPITHELIM IN THE ABSENCE OF NUCLEAR TRANSLOCATION OF NF-KB

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Airway epithelial cells respond to certain environmental stresses by mounting a proinflammatory response, which is characterized by enhanced synthesis and release of the neutrophil chemotactic and activating factor interleukin-8 (IL-8). IL-8 expression is regulated at the transcr...

IL-4 and IL-13 mediated down-regulation of CD8 expression levels can dampen anti-viral CD8⁺ T cell avidity following HIV-1 recombinant pox viral vaccination.

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Wijesundara, Danushka K; Jackson, Ronald J; Tscharke, David C; Ranasinghe, Charani

2013-09-23

We have shown that mucosal HIV-1 recombinant pox viral vaccination can induce high, avidity HIV-specific CD8(+) T cells with reduced interleukin (IL)-4 and IL-13 expression compared to, systemic vaccine delivery. In the current study how these cytokines act to regulate anti-viral CD8(+) T, cell avidity following HIV-1 recombinant pox viral prime-boost vaccination was investigated. Out of a panel of T cell avidity markers tested, only CD8 expression levels were found to be enhanced on, KdGag197-205 (HIV)-specific CD8(+) T cells obtained from IL-13(-/-), IL-4(-/-) and signal transducer and, activator of transcription of 6 (STAT6)(-/-) mice compared to wild-type (WT) controls following, vaccination. Elevated CD8 expression levels in this instance also correlated with polyfunctionality, (interferon (IFN)-γ, tumour necorsis factor (TNF)-α and IL-2 production) and the avidity of HIVspecific CD8(+) T cells. Furthermore, mucosal vaccination and vaccination with the novel adjuvanted IL-13 inhibitor (i.e. IL-13Rα2) vaccines significantly enhanced CD8 expression levels on HIV-specific CD8(+), T cells, which correlated with avidity. Using anti-CD8 antibodies that blocked CD8 availability on CD8(+), T cells, it was established that CD8 played an important role in increasing HIV-specific CD8(+) T cell avidity and polyfunctionality in IL-4(-/-), IL-13(-/-) and STAT6(-/-) mice compared to WT controls, following vaccination. Collectively, our data demonstrate that IL-4 and IL-13 dampen CD8 expression levels on anti-viral CD8(+) T cells, which can down-regulate anti-viral CD8(+) T cell avidity and, polyfunctionality following HIV-1 recombinant pox viral vaccination. These findings can be exploited to, design more efficacious vaccines not only against HIV-1, but many chronic infections where high, avidity CD8(+) T cells help protection. Copyright © 2013 Elsevier Ltd. All rights reserved.

Elevated serum high-sensitivity C-reactive protein levels in fibromyalgia syndrome patients correlate with body mass index, interleukin-6, interleukin-8, erythrocyte sedimentation rate.

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Xiao, Yangming; Haynes, Wanda L; Michalek, Joel E; Russell, I Jon

2013-05-01

The levels of several inflammatory cytokines are abnormal in many patients with the fibromyalgia syndrome (FMS) and may play a role in its pathogenesis. The inflammatory marker C-reactive protein (CRP) is associated with the disease activity in patients with inflammatory rheumatic diseases, but its role in FMS is unknown. We undertook this study to determine whether high-sensitivity CRP (hsCRP) is elevated in FMS and whether its levels relate to key biologic or clinical measures. One hundred and five patients with FMS (1990 ACR criteria) and 61 healthy normal controls (HNC) at a ratio of 2:1 were recruited. The serum concentrations of hsCRP, interleukin-8 (IL-8), and interleukin-6 (IL-6) were assessed using enzyme-linked immunosorbent assays. The hsCRP levels were marginally higher in FMS than in HNC (p = 0.06) and its abnormality rate (>1.5 SD above the HNC mean) was significantly higher in FMS (25 %) compared with HNC (6.8 %) (p = 0.03). Serum IL-8 levels, IL-6 levels, and erythrocyte sedimentation rate (ESR) in FMS did not differ from those in HNC. Body mass index (BMI), ESR, IL-8, and IL-6 levels correlated with hsCRP levels in FMS. No associations were found between hsCRP and age, gender, ethnicity, or other clinical measures. Serum CRP levels were higher in FMS and significantly correlated with BMI, ESR, IL-8, and IL-6 levels, suggesting that inflammation may contribute to the symptoms in some FMS patients, particularly those who are obese. Weight loss and therapies directed against inflammation may be useful in the management of FMS patients with elevated hsCRP.

IL-8 and MCP Gene Expression and Production by LPS-Stimulated Human Corneal Stromal Cells

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Roni M. Shtein

2012-01-01

Full Text Available Purpose. To determine time course of effect of lipopolysaccharide (LPS on production of interleukin-8 (IL-8 and monocyte chemotactic protein (MCP by cultured human corneal stromal cells. Methods. Human corneal stromal cells were harvested from donor corneal specimens, and fourth to sixth passaged cells were used. Cell cultures were stimulated with LPS for 2, 4, 8, and 24 hours. Northern blot analysis of IL-8 and MCP gene expression and ELISA for IL-8 and MCP secretion were performed. ELISA results were analyzed for statistical significance using two-tailed Student's t-test. Results. Northern blot analysis demonstrated significantly increased IL-8 and MCP gene expression after 4 and 8 hours of exposure to LPS. ELISA for secreted IL-8 and MCP demonstrated statistically significant increases (P<0.05 after corneal stromal cell stimulation with LPS. Conclusions. This paper suggests that human corneal stromal cells may participate in corneal inflammation by secreting potent leukocyte chemotactic and activating proteins in a time-dependent manner when exposed to LPS.

IL-8 expression and its possible relationship with estrogen-receptor-negative status of breast cancer cells

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Freund, Ariane; Chauveau, Corine; Brouillet, Jean-Paul; Lucas, Annick; Lacroix, Matthieu; Licznar, Anne; Vignon, Françoise; Lazennec, Gwendal

2003-01-01

Estrogen receptor (ER) status is an important parameter in breast cancer management as ER-positive breast cancers have a better prognosis than ER-negative tumors. This difference comes essentially from the lower aggressiveness and invasiveness of ER-positive tumors. Here, we demonstrate, that IL-8 was clearly overexpressed in most ER-negative breast, ovary cell lines and breast tumor samples tested, whereas no significant IL-8 level could be detected in ER-positive breast or ovarian cell lines. We have also cloned human IL-8 from ER-negative MDA-MB-231 cells and we show that IL-8 produced by breast cancer cells is identical to monocyte-derived IL-8. Interestingly, the invasion potential of ER-negative breast cancer cells is associated at least in part with expression of interleukin-8 (IL-8), but not with IL-8 receptors levels. Moreover, IL-8 increases the invasiveness of ER-positive breast cancer cells by 2 fold, thus confirming the invasion-promoting role of IL-8. On the other hand, exogenous expression of estrogen receptors in ER-negative cells led to a decrease of IL-8 levels. In summary, our data show that IL-8 expression is negatively linked to ER-status of breast and ovarian cancer cells. We also support the idea that IL-8 expression is associated with a higher invasiveness potential of cancer cells in vitro, which suggests that IL-8 could be a novel marker of tumor aggressiveness. PMID:12527894

Interleukin-8 (IL-8) over-production and autocrine cell activation are key factors in monomethylarsonous acid [MMA(III)]-induced malignant transformation of urothelial cells

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Escudero-Lourdes, C.; Wu, T.; Camarillo, J.M.; Gandolfi, A.J.

2012-01-01

The association between chronic human exposure to arsenicals and bladder cancer development is well recognized; however, the underlying molecular mechanisms have not been fully determined. We propose that inflammatory responses can play a pathogenic role in arsenic-related bladder carcinogenesis. In previous studies, it was demonstrated that chronic exposure to 50 nM monomethylarsenous acid [MMA(III)] leads to malignant transformation of an immortalized model of urothelial cells (UROtsa), with only 3 mo of exposure necessary to trigger the transformation-related changes. In the three-month window of exposure, the cells over-expressed pro-inflammatory cytokines (IL-1β, IL-6 and IL-8), consistent with the sustained activation of NFKβ and AP1/c-jun, ERK2, and STAT3. IL-8 was over-expressed within hours after exposure to MMA(III), and sustained over-expression was observed during chronic exposure. In this study, we profiled IL-8 expression in UROtsa cells exposed to 50 nM MMA(III) for 1 to 5 mo. IL-8 expression was increased mainly in cells after 3 mo MMA(III) exposure, and its production was also found increased in tumors derived from these cells after heterotransplantation in SCID mice. UROtsa cells do express both receptors, CXCR1 and CXCR2, suggesting that autocrine cell activation could be important in cell transformation. Supporting this observation and consistent with IL-8 over-expression, CXCR1 internalization was significantly increased after three months of exposure to MMA(III). The expression of MMP-9, cyclin D1, bcl-2, and VGEF was significantly increased in cells exposed to MMA(III) for 3 mo, but these mitogen-activated kinases were significantly decreased after IL-8 gene silencing, together with a decrease in cell proliferation rate and in anchorage-independent colony formation. These results suggest a relevant role of IL-8 in MMA(III)-induced UROtsa cell transformation. -- Highlights: ► IL-8 is over-expressed in human MMA(III)-exposed urothelial

Cleavage/alteration of interleukin-8 by matrix metalloproteinase-9 in the female lower genital tract.

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Zariffard, M Reza; Anastos, Kathryn; French, Audrey L; Munyazesa, Elisaphane; Cohen, Mardge; Landay, Alan L; Spear, Gregory T

2015-01-01

Interleukin-8 (IL-8, CXCL8) plays important roles in immune responses at mucosal sites including in the lower genital tract. Since several types of bacteria produce proteases that cleave IL-8 and many types of bacteria can be present in lower genital tract microbiota, we assessed genital fluids for IL-8 cleavage/alteration. Genital fluids collected by lavage from 200 women (23 HIV-seronegative and 177 HIV-seropositive) were tested for IL-8 cleavage/alteration by ELISA. IL-8 cleaving/altering activity was observed in fluids from both HIV-positive (28%) and HIV-negative women (35%). There was no clear relationship between the activity and the types of bacteria present in the lower genital tract as determined by high-throughput sequencing of the 16S rRNA gene. Protease inhibitors specific for matrix metalloproteinases (MMPs) reduced the activity and a multiplex assay that detects both inactive and active MMPs showed the presence of multiple MMPs, including MMP-1, -3, -7, -8, -9, -10 and -12 in genital secretions from many of the women. The IL-8-cleaving/altering activity significantly correlated with active MMP-9 as well as with cleavage of a substrate that is acted on by several active MMPs. These studies show that multiple MMPs are present in the genital tract of women and strongly suggest that MMP-9 in genital secretions can cleave IL-8 at this mucosal site. These studies suggest that MMP-mediated cleavage of IL-8 can modulate inflammatory responses in the lower genital tract.

IL-8 as a urinary biomarker for the detection of bladder cancer

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Urquidi Virginia

2012-05-01

Full Text Available Abstract Background Current urine-based assays for bladder cancer (BCa diagnosis lack accuracy, so the search for improved biomarkers continues. Through genomic and proteomic profiling of urine, we have identified a panel of biomarkers associated with the presence of BCa. In this study, we evaluated the utility of three of these biomarkers, interleukin 8 (IL-8, Matrix metallopeptidase 9 (MMP-9 and Syndecan in the diagnosis of BCa through urinalysis. Methods Voided urines from 127 subjects, cancer subjects (n = 64, non-cancer subjects (n = 63 were analyzed. The protein concentrations of IL-8, MMP-9, and Syndecan were assessed by enzyme-linked immunosorbent assay (ELISA. Data were also compared to a commercial ELISA-based BCa detection assay (BTA-Trak© and urinary cytology. We used the area under the curve of a receiver operating characteristic (AUROC to compare the performance of each biomarker. Results Urinary protein concentrations of IL-8, MMP-9 and BTA were significantly elevated in BCa subjects. Of the experimental markers compared to BTA-Trak©, IL-8 was the most prominent marker (AUC; 0.79; 95% confidence interval [CI], 0.72-0.86. Multivariate regression analysis revealed that only IL-8 (OR; 1.51; 95% CI, 1.16-1.97, p = 0.002 was an independent factor for the detection of BCa. Conclusions These results suggest that the measurement of IL-8 in voided urinary samples may have utility for urine-based detection of BCa. These findings need to be confirmed in a larger, prospective cohort.

Role of the Mycoplasma pneumoniae/Interleukin-8/Neutrophil Axis in the Pathogenesis of Pneumonia.

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Zhengrong Chen

Full Text Available Neutrophil infiltration is the characteristic pathological feature of M. pneumoniae pneumonia (MPP. This study aimed to explore the associations among neutrophil activity, clinical presentation, and role of the M. pneumoniae/interleukin-8 (IL-8/neutrophil axis in the pathogenesis of MPP. A total of 42 patients with MPP were prospectively enrolled in the study. Neutrophil activity, including matrix metalloproteinase-9 (MMP-9, myeloperoxidase (MPO, and neutrophil elastase (NE, were measured. Clinical information was collected for all patients and control group. In vitro, IL-8 production was measured at different time points after M. pneumoniae infection of bronchial epithelial cells, and neutrophil activity was analyzed after IL-8 stimulation. The percentage of neutrophil in the bronchoalveolar lavage fluid was higher in the group of patients with high levels of M. pneumoniae DNA than in those with low levels of M. pneumoniae DNA (P < 0.05. IL-8, MMP-9, and NE in patients with MPP significantly increased compared with controls and decreased after treatment (P < 0.05. MPO and MMP-9 were associated with duration of fever (r = 0.332, P < 0.05 and length of stay (r = 0.342, P < 0.05, respectively. In vitro, M. pneumoniae induced IL-8 production by bronchial epithelial cells in a time dependent manner. MPO, MMP-9 and NE production by neutrophils significantly increased compared with medium controls after IL-8 stimulation. In summary, the M. pneumoniae/IL-8/neutrophil axis likely plays a vital role in the pathogenesis of MPP.

Molecular characterization of Legionella pneumophila-induced interleukin-8 expression in T cells

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Mukaida Naofumi

2010-01-01

Full Text Available Abstract Background Legionella pneumophila is the causative agent of human Legionnaire's disease. During infection, the bacterium invades macrophages and lung epithelial cells, and replicates intracellularly. However, little is known about its interaction with T cells. We investigated the ability of L. pneumophila to infect and stimulate the production of interleukin-8 (IL-8 in T cells. The objective of this study was to assess whether L. pneumophila interferes with the immune system by interacting and infecting T cells. Results Wild-type L. pneumophila and flagellin-deficient Legionella, but not L. pneumophila lacking a functional type IV secretion system Dot/Icm, replicated in T cells. On the other hand, wild-type L. pneumophila and Dot/Icm-deficient Legionella, but not flagellin-deficient Legionella or heat-killed Legionella induced IL-8 expression. L. pneumophila activated an IL-8 promoter through the NF-κB and AP-1 binding regions. Wild-type L. pneumophila but not flagellin-deficient Legionella activated NF-κB, p38 mitogen-activated protein kinase (MAPK, Jun N-terminal kinase (JNK, and transforming growth factor β-associated kinase 1 (TAK1. Transfection of dominant negative mutants of IκBα, IκB kinase, NF-κB-inducing kinase, TAK1, MyD88, and p38 MAPK inhibited L. pneumophila-induced IL-8 activation. Inhibitors of NF-κB, p38 MAPK, and JNK blocked L. pneumophila-induced IL-8 expression. In addition, c-Jun, JunD, cyclic AMP response element binding protein, and activating transcription factor 1, which are substrates of p38 MAPK and JNK, bound to the AP-1 site of the IL-8 promoter. Conclusions Taken together, L. pneumophila induced a flagellin-dependent activation of TAK1, p38 MAPK, and JNK, as well as NF-κB and AP-1, which resulted in IL-8 production in human T cells, presumably contributing to the immune response in Legionnaire's disease.

Expression of IL-8, IL-6 and IL-1β in Tears as a Main Characteristic of the Immune Response in Human Microbial Keratitis

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Santacruz, Concepcion; Linares, Marisela; Garfias, Yonathan; Loustaunau, Luisa M.; Pavon, Lenin; Perez-Tapia, Sonia Mayra; Jimenez-Martinez, Maria C.

2015-01-01

Corneal infections are frequent and potentially vision-threatening diseases, and despite the significance of the immunological response in animal models of microbial keratitis (MK), it remains unclear in humans. The aim of this study was to describe the cytokine profile of tears in patients with MK. Characteristics of ocular lesions such as size of the epithelial defect, stromal infiltration, and hypopyon were analyzed. Immunological evaluation included determination of interleukine (IL)-1β, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor (TNF)-α in tear samples obtained from infected eyes of 28 patients with MK and compared with their contralateral non-infected eyes. Additionally, frequency of CD4+, CD8+, CD19+ and CD3−CD56+ cells was also determined in peripheral blood mononuclear cells in patients with MK, and compared with 48 healthy controls. Non-significant differences were observed in the size of the epithelial defect, stromal infiltration, and hypopyon. Nevertheless, we found an immunological profile apparently related to MK etiology. IL-8 > IL-6 in patients with bacterial keratitis; IL-8 > IL-6 > IL-1β and increased frequency of circulating CD3−CD56+ NK cells in patients with gram-negative keratitis; and IL-8 = IL-6 > IL-1β in patients with fungal keratitis. Characterization of tear cytokines from patients with MK could aid our understanding of the immune pathophysiological mechanisms underlying corneal damage in humans. PMID:25741769

Molecular cloning of interleukin-1β, interleukin-8, and tumor necrosis factor-α of bighorn sheep (Ovis canadensis) and comparison with those of other species.

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Herndon, Caroline N; Dassanayake, Rohana P; Foreyt, William J; Srikumaran, Subramaniam

2010-11-15

The susceptibility to, and pathology induced by, Mannheimia haemolytica infection in bighorn sheep (BHS) and domestic sheep (DS) are distinctly different. Bighorn sheep are particularly susceptible to pneumonia caused by M. haemolytica, and the pneumonic lesions in infected BHS are more severe than those in DS. The molecular basis for this disparity has not been elucidated. Proinflammatory cytokines have been implicated in the pathogenesis of multiple lung diseases of humans and animals. It is possible that the enhanced pathology observed in the pneumonic lungs of M. haemolytica-infected BHS, in comparison to that of DS, is due to comparatively higher levels of proinflammatory cytokine expression in BHS. As the first step towards elucidating this concept, we have cloned and sequenced the cDNA encoding the cytokines interleukin-1β (IL-1β), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) of BHS. The cDNA of BHS IL-1β, IL-8, and TNF-α consists of 801, 306, and 705 base pairs encoding 266, 101, and 234 amino acids, respectively. The availability of cDNA encoding IL-1β, IL-8, and TNF-α of BHS should facilitate the elucidation of the role of these cytokines in the differential pathology induced by M. haemolytica infection in BHS and DS. Copyright © 2010 Elsevier B.V. All rights reserved.

Short-term exposure to oleandrin enhances responses to IL-8 by increasing cell surface IL-8 receptors

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Raviprakash, Nune; Manna, Sunil Kumar

2014-01-01

BACKGROUND AND PURPOSE One of the first steps in host defence is the migration of leukocytes. IL-8 and its receptors are a chemokine system essential to such migration. Up-regulation of these receptors would be a viable strategy to treat dysfunctional host defence. Here, we studied the effects of the plant glycoside oleandrin on responses to IL-8 in a human monocytic cell line. EXPERIMENTAL APPROACH U937 cells were incubated with oleandrin (1-200 ng mL−1) for either 1 h (pulse) or for 24 h (non-pulse). Apoptosis; activation of NF-κB, AP-1 and NFAT; calcineurin activity and IL-8 receptors (CXCR1 and CXCR2) were measured using Western blotting, RT-PCR and reporter gene assays. KEY RESULTS Pulse exposure to oleandrin did not induce apoptosis or cytoxicity as observed after non-pulse exposure. Pulse exposure enhanced activation of NF-κB induced by IL-8 but not that induced by TNF-α, IL-1, EGF or LPS. Exposure to other apoptosis-inducing compounds (azadirachtin, resveratrol, thiadiazolidine, or benzofuran) did not enhance activation of NF-κB. Pulse exposure to oleandrin increased expression of IL-8 receptors and chemotaxis, release of enzymes and activation of NF-κB, NFAT and AP-1 along with increased IL-8-mediated calcineurin activation, and wound healing. Pulse exposure increased numbers of cell surface IL-8 receptors. CONCLUSIONS AND IMPLICATIONS Short-term (1 h; pulse) exposure to a toxic glycoside oleandrin, enhanced biological responses to IL-8 in monocytic cells, without cytoxicity. Pulse exposure to oleandrin could provide a viable therapy for those conditions where leukocyte migration is defective. PMID:24172227

fMLP-Induced IL-8 Release Is Dependent on NADPH Oxidase in Human Neutrophils

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María A. Hidalgo

2015-01-01

Full Text Available N-Formyl-methionyl-leucyl-phenylalanine (fMLP and platelet-activating factor (PAF induce similar intracellular signalling profiles; but only fMLP induces interleukin-8 (IL-8 release and nicotinamide adenine dinucleotide phosphate reduced (NADPH oxidase activity in neutrophils. Because the role of ROS on IL-8 release in neutrophils is until now controversial, we assessed if NADPH oxidase is involved in the IL-8 secretions and PI3K/Akt, MAPK, and NF-κB pathways activity induced by fMLP. Neutrophils were obtained from healthy volunteers. IL-8 was measured by ELISA, IL-8 mRNA by qPCR, and ROS production by luminol-amplified chemiluminescence, reduction of ferricytochrome c, and FACS. Intracellular pH changes were detected by spectrofluorescence. ERK1/2, p38 MAPK, and Akt phosphorylation were analysed by immunoblotting and NF-κB was analysed by immunocytochemistry. Hydroxy-3-methoxyaceto-phenone (HMAP, diphenyleneiodonium (DPI, and siRNA Nox2 reduced the ROS and IL-8 release in neutrophils treated with fMLP. HMAP, DPI, and amiloride (a Na+/H+ exchanger inhibitor inhibited the Akt phosphorylation and did not affect the p38 MAPK and ERK1/2 activity. DPI and HMAP reduced NF-κB translocation induced by fMLP. We showed that IL-8 release induced by fMLP is dependent on NADPH oxidase, and ROS could play a redundant role in cell signalling, ultimately activating the PI3K/Akt and NF-κB pathways in neutrophils.

Sequential cancer immunotherapy: targeted activity of dimeric TNF and IL-8

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Adrian, Nicole; Siebenborn, Uta; Fadle, Natalie; Plesko, Margarita; Fischer, Eliane; Wüest, Thomas; Stenner, Frank; Mertens, Joachim C.; Knuth, Alexander; Ritter, Gerd; Old, Lloyd J.; Renner, Christoph

2009-01-01

Polymorphonuclear neutrophils (PMNs) are potent effectors of inflammation and their attempts to respond to cancer are suggested by their systemic, regional and intratumoral activation. We previously reported on the recruitment of CD11b+ leukocytes due to tumor site-specific enrichment of TNF activity after intravenous administration of a dimeric TNF immunokine with specificity for fibroblast activation protein (FAP). However, TNF-induced chemo-attraction and extravasation of PMNs from blood into the tumor is a multistep process essentially mediated by interleukin 8. With the aim to amplify the TNF-induced and IL-8-mediated chemotactic response, we generated immunocytokines by N-terminal fusion of a human anti-FAP scFv fragment with human IL-8 (IL-872) and its N-terminally truncated form IL-83-72. Due to the dramatic difference in chemotaxis induction in vitro, we favored the mature chemokine fused to the anti-FAP scFv for further investigation in vivo. BALB/c nu/nu mice were simultaneously xenografted with FAP-positive or -negative tumors and extended chemo-attraction of PMNs was only detectable in FAP-expressing tissue after intravenous administration of the anti-FAP scFv-IL-872 construct. As TNF-activated PMNs are likewise producers and primary targets for IL-8, we investigated the therapeutic efficacy of co-administration of both effectors: Sequential application of scFv-IL-872 and dimeric IgG1-TNF fusion proteins significantly enhanced anti-tumor activity when compared either to a single effector treatment regimen or sequential application of non-targeted cytokines, indicating that the tumor-restricted sequential application of IL-872 and TNF is a promising approach for cancer therapy. PMID:19267427

IL-8 Expression in Granulocytic Epithelial Lesions of Idiopathic Duct-centric Pancreatitis (Type 2 Autoimmune Pancreatitis).

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Ku, Yuna; Hong, Seung-Mo; Fujikura, Kohei; Kim, Sung Joo; Akita, Masayuki; Abe-Suzuki, Shiho; Shiomi, Hideyuki; Masuda, Atsuhiro; Itoh, Tomoo; Azuma, Takeshi; Kim, Myung-Hwan; Zen, Yoh

2017-08-01

Type 2 autoimmune pancreatitis (type 2 AIP) develops in isolation or sometimes in association with ulcerative colitis. Its diagnosis requires the histologic confirmation of granulocytic epithelial lesions (GELs) with no diagnostic biomarker currently available. This study aimed to elucidate the tissue expression of cytokines and their diagnostic value in this condition. In quantitative polymerase chain reaction for multiple cytokines using tissue-derived mRNA, the expression level of interleukin (IL)-8 was markedly higher in type 2 AIP than in type 1 AIP (Ppancreatitis adjacent to pancreatic cancers (peritumoral pancreatitis) exhibited IL-8 expression in the epithelium (3/12; 25%) and inflammatory cells (10/12; 83%), expression levels were significantly lower than those in type 2 AIP (Ppancreatitis with 92% sensitivity and 92% to 100% specificity. Furthermore, CD3/IL-8-coexpressing lymphocytes were almost restricted to type 2 AIP. Interestingly, a similar pattern of IL-8 expression was also observed in colonic biopsies of ulcerative colitis. In conclusion, the overexpression of IL-8 may underlie the development of GELs in type 2 AIP, and IL-8 immunostaining or IL-8/CD3 double staining may become an ancillary method for its diagnosis. The similar expression pattern of IL-8 in ulcerative colitis also suggests a pathogenetic link between the 2 conditions.

Purine-Metabolizing Ectoenzymes Control IL-8 Production in Human Colon HT-29 Cells

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Fariborz Bahrami

2014-01-01

Full Text Available Interleukin-8 (IL-8 plays key roles in both chronic inflammatory diseases and tumor modulation. We previously observed that IL-8 secretion and function can be modulated by nucleotide (P2 receptors. Here we investigated whether IL-8 release by intestinal epithelial HT-29 cells, a cancer cell line, is modulated by extracellular nucleotide metabolism. We first identified that HT-29 cells regulated adenosine and adenine nucleotide concentration at their surface by the expression of the ectoenzymes NTPDase2, ecto-5′-nucleotidase, and adenylate kinase. The expression of the ectoenzymes was evaluated by RT-PCR, qPCR, and immunoblotting, and their activity was analyzed by RP-HPLC of the products and by detection of Pi produced from the hydrolysis of ATP, ADP, and AMP. In response to poly (I:C, with or without ATP and/or ADP, HT-29 cells released IL-8 and this secretion was modulated by the presence of NTPDase2 and adenylate kinase. Taken together, these results demonstrate the presence of 3 ectoenzymes at the surface of HT-29 cells that control nucleotide levels and adenosine production (NTPDase2, ecto-5′-nucleotidase and adenylate kinase and that P2 receptor-mediated signaling controls IL-8 release in HT-29 cells which is modulated by the presence of NTPDase2 and adenylate kinase.

The changes of sputum IL-8 and TNF-α level in COPD patients and their clinical value

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Zhuo Liankun; Wang Xiaoli; Zhang Feng; Zhou Xiao

2011-01-01

To investigate the changes and role of interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) in the diagnosis and therapy of COPD, the levels of IL-8 and TNF-α in serum and sputum samples in 58 COPD cases during different therapy periods were detected by radioimmunoassay. The results showed that the sputum IL-8 and TNF-α levels in COPD patients at the attack aggressive stage were significantly higher than those in the stable stage, which were in accord with those changes in serum samples. Furthermore, the changes of IL-8 and TNF-α levels in sputum samples were earlier than the changes in serum samples. The changes of sputum IL-8 and TNF-α levels in COPD patients may play a more important role than the changes of serum samples in the diagnosis and prognosis of patients with COPD. (authors)

Plasma Interleukin-8 and Endothelin-1 in Symptomatic and Asymptomatic Children

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Radwan, Z.; El-Abiad, N.; Soliman, M. S.; Ali, A.I.; Ali, G.S.

2004-01-01

This study was designed to evaluate the extent to which IL-8 and endothelin-1 are involved in the development of acute exacerbation of atopic asthma. Two asthmatic groups, each of 20 patients were studied, the asymptomatic group where patients were free of symptoms and the symptomatic group where patients were suffering from acute exacerbation of their asthma. Both of asthmatic groups were subclassified into mild and moderate subgroups, each of 10 patients according to the asthma severity. All subjects were subjected to chest X-ray and peak expiratory flow rate (PEFR) recording for sub-classification of patients, skin prick testing using common allergens (patients only) for the identification of atopic asthmatic patients and laboratory investigations including complete blood count (CBC), absolute eosi-nophil count (AEC), urine and stool exam-ination, total serum 1 gE level, plasma inter-leukin-8 (IL-8) level and plasma endothelin-1 (ET-1) level. The data obtained revealed non-significant differences between the studied groups as regards AEC, while serum total 1 gE of the asthmatic groups showed highly significant elevations in comparison to control group. Also, There were highly significant elevations in plasma endothelin-1 and plasma IL-8 levels of the symptomatic asthmatic subgroups in comparison to control group and asymptomatic asthmatic subgroups in comparison to control group and asymptomatic asthmatic subgroups. In conclusion: although it is clear now that IL-8 and ET-1 are involved in acute exacerbation of atopic asthmatic patients, a causal link between those mediators and development of the exacerbation has not been definitively established. Surely, those mediators, their receptors, synthesis and degradation pathways offer potentially important therapeutic targets

Stimulation of epithelial cell matrix metalloproteinase (MMP-2, -9, -13) and interleukin-8 secretion by fusobacteria.

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Gursoy, U K; Könönen, E; Uitto, V-J

2008-10-01

Bacterial pathogens involved in periodontal diseases exert their destructive effects primarily by stimulating the host cells to increase their secretion of proinflammatory cytokines and matrix metalloproteinases (MMPs). This study aimed to determine the epithelial cell matrix metalloproteinase and interleukin-8 (IL-8) secretion upon exposure to fusobacteria. Eight different oral and non-oral Fusobacterium strains were incubated with HaCaT epithelial cells. Gelatin zymography and Western blot analysis were performed to detect collagenase 3 (MMP-13), gelatinase A (MMP-2), gelatinase B (MMP-9), and IL-8 secretion by epithelial cells. All Fusobacterium strains, especially Fusobacterium necrophorum ATCC 25286, Fusobacterium nucleatum ATCC 25586, and Fusobacterium varium ATCC 51644, increased MMP-9 and MMP-13 secretion. Fusobacterium simiae ATCC 33568, and to a lesser extent F. nucleatum and F. necrophorum, increased epithelial MMP-2 secretion. F. nucleatum and F. necrophorum also increased IL-8 secretion. F. varium ATCC 27725, a strain that only weakly stimulated MMP production, strongly increased the IL-8 production, suggesting that their expression is differently regulated. We conclude that the pathogenic potential of fusobacteria may partly result from their ability to stimulate secretion of MMP-9, MMP-13, and IL-8 from epithelial cells.

Identification of interleukin-8 converting enzyme as cathepsin L.

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Ohashi, Kensaku; Naruto, Masanobu; Nakaki, Toshio; Sano, Emiko

2003-06-26

IL-8 is produced by various cells, and the NH(2)-terminal amino acid sequence of IL-8 displays heterogeneity among cell types. The mature form of IL-8 has 72 amino acids (72IL-8), while a precursor form (77IL-8) of IL-8 has five additional amino acids to the 72IL-8 NH(2)-terminal. However, it has been unclear how IL-8 is processed to yield the mature form. In this study, converting enzyme was purified as a single 31-kDa band on silver-stained polyacrylamide gel from 160 l of cultured fibroblast supernatant by sequential chromatography. NH(2)-terminal amino acid sequence analysis revealed a sequence, EAPRSVDWRE, which was identified as a partial sequence of cathepsin L. Polyclonal antibodies raised against cathepsin L recognized the purified converting enzyme on Western blot. Moreover, human hepatic cathepsin L cleaved 77IL-8 between Arg(5) and Ser(6), which is the same cleavage site as the putative converting enzyme, resulting in 72IL-8 formation. These data indicate that the converting enzyme of the partially purified fraction of the human fibroblast culture supernatant was cathepsin L. Furthermore, 72IL-8 was sevenfold more potent than 77IL-8 in a neutrophil chemotaxis assay. These results show that cathepsin L is secreted from human fibroblasts in response to external stimuli and plays an important role in IL-8 processing in inflammatory sites.

Grain dust induces IL-8 production from bronchial epithelial cells: the effect of dexamethasone on IL-8 production.

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Park, H S; Suh, J H; Kim, H Y; Kwon, O J; Choi, D C

1999-04-01

Recent publications have suggested an active participation of neutrophils to induce bronchoconstriction after inhalation of grain dust (GD). To further understand the role of neutrophils in the pathogenesis of GD-induced asthma, this investigation was designed to determine whether human bronchial epithelial cells could produce IL-8 production and to observe the effect of dexamethasone on IL-8 production. We cultured Beas-2B, a bronchial epithelial cell line. To observe GD-induced responses, four concentrations (1 to 200 microg/mL) of GD were incubated for 24 hours and compared with those without incubation of GD. To evaluate the effect of pro-inflammatory cytokines on IL-8 production, epithelial cells were incubated with peripheral blood mononuclear cell (PBMC) culture supernatant, which was derived from the culture of PBMC from a GD-induced asthmatic subject under the exposure to 10 microg/mL of GD, and compared with those cultured without addition of PBMC supernatant. The level of released IL-8 in the supernatant was measured by enzyme-linked immunosorbent assay. To evaluate the effect of dexamethasone on IL-8 production, four concentrations (5 to 5000 ng/mL) of dexamethasone were pre-incubated for 24 hours and the same experiments were repeated. There was significant production of IL-8 from bronchial epithelial cells with additions of GD in a dose-dependent manner (P < .05), which was significantly augmented with additions of PBMC supernatant (P < .05) at each concentration. Compared with the untreated sample, pretreatment of dexamethasone could induced a remarkable inhibitions (15% to 55%) of IL-8 production from bronchial epithelial cells in a dose-dependent manner. These results suggest that IL-8 production from bronchial epithelial cells may contribute to neutrophil recruitment occurring in GD-induced airway inflammation. The downregulation of IL-8 production by dexamethasone from bronchial epithelial cells may contribute to the efficacy of this compound in

Abnormal peritoneal regulation of chemokine activation-The role of IL-8 in pathogenesis of endometriosis.

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Sikora, Justyna; Smycz-Kubańska, Marta; Mielczarek-Palacz, Aleksandra; Kondera-Anasz, Zdzisława

2017-04-01

Endometriosis is a chronic inflammatory disease associated with an impairment in immune response. Disorders in the peritoneal fluid and ectopic endometrium macrophage populations and their secretory products create a specific microenvironment inducing the development of the disease. The important factors involved in inflammation associated with endometriosis are chemokines, especially interleukin (IL)-8. For this reason, the current study briefly reviews the role of IL-8 in the pathogenesis of endometriosis. A systematic review was done on all published studies that compared IL-8 expression and concentration in patients with and without endometriosis to evaluate their potential as biomarkers for the disease. IL-8 induces chemotaxis of neutrophils and other immune cells; also, it is a potent angiogenic agent. Most researchers pointed to the increased peritoneal and serum IL-8 levels and showed correlation with the severity of the disease, size and number of the active lesions. IL-8 takes part in all processes during the development of the disease: adhesion, invasion, and implantation of ectopic tissue. Additionally, the chemokine plays a role in growth and maintenance of ectopic endometrial tissue directly affecting endometrial cell proliferation. IL-8 might also protect ectopic cells against death by apoptosis. It may act as an autocrine growth factor in the endometrium and promotes the vicious circle of endometrial cell attachment and, in consequence, may lead to a transformation from acute to chronic inflammation stage. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinical significance of changes of serum gastrin (gas) transforming growth factor-alpha (TGF-α) and interleukin-8 (IL-8) levels after treatment in patients with peptic ulcer

International Nuclear Information System (INIS)

Zhou Yuyang

2007-01-01

Objective: To explore the clinical significance of changes of serum Gas, TGF-α and IL-8 levels in patients with peptic ulcer. Methods: Serum Gas, TGF-α (with RIA), IL-8 (with ELISA) levels were determined in 56 patients with peptic ulcer both before and after treatment as well as in 35 controls. Results: Before treatment the serum Gas and IL-8 levels were significantly higher than those in controls (P 0.05). Conclusion: Serum Gas, TGF-α and IL-8 levels were closely related to the diseases process of peptic ulcer and were of prognostic values. (authors)

Genetic characterization of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18) with relevant biological roles in lagomorphs

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Neves, Fabiana; Abrantes, Joana; Almeida, Tereza; de Matos, Ana Lemos; Costa, Paulo P

2015-01-01

ILs, as essential innate immune modulators, are involved in an array of biological processes. In the European rabbit (Oryctolagus cuniculus) IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18 have been implicated in inflammatory processes and in the immune response against rabbit hemorrhagic disease virus and myxoma virus infections. In this study we characterized these ILs in six Lagomorpha species (European rabbit, pygmy rabbit, two cottontail rabbit species, European brown hare and American pika). Overall, these ILs are conserved between lagomorphs, including in their exon/intron structure. Most differences were observed between leporids and American pika. Indeed, when comparing both, some relevant differences were observed in American pika, such as the location of the stop codon in IL-1α and IL-2, the existence of a different transcript in IL8 and the number of cysteine residues in IL-1β. Changes at N-glycosylation motifs were also detected in IL-1, IL-10, IL-12B and IL-15. IL-1α is the protein that presents the highest evolutionary distances, which is in contrast to IL-12A where the distances between lagomorphs are the lowest. For all these ILs, sequences of human and European rabbit are more closely related than between human and mouse or European rabbit and mouse. PMID:26395994

High serum interleukin-8 levels in Afro-Caribbean women with pre-eclampsia. Relations with tumor necrosis factor-alpha, Duffy negative phenotype and von Willebrand factor

NARCIS (Netherlands)

Velzing-Aarts, FV; Muskiet, FAJ; van der Dijs, FPL; Duits, AJ

PROBLEM: Pre-eclampsia is characterized by neutrophil activation. Interleukin-8 (IL-8) is a strong neutrophil chemo-attractant and activator. METHOD OF STUDY: We measured serum IL-8 in 13 pre-eclamptic Afro-Caribbean women and 13 gestational age-, race- and parity-matched normotensive and

Association of interleukin-8 and neutrophils with nasal symptom severity during acute respiratory infection.

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Henriquez, Kelsey M; Hayney, Mary S; Xie, Yaoguo; Zhang, Zhengjun; Barrett, Bruce

2015-02-01

Using a large data set (n = 811), the relationship between acute respiratory infection illness severity and inflammatory biomarkers was investigated to determine whether certain symptoms are correlated more closely than others with the inflammatory biomarkers, interleukin-8 (IL-8) and nasal neutrophils. Participants with community acquired acute respiratory infection underwent nasal lavage for IL-8 and neutrophil testing, in addition to multiplex polymerase chain reaction (PCR) methods for the detection and identification of respiratory viruses. Information about symptoms was obtained throughout the duration of the illness episode using the well-validated Wisconsin Upper Respiratory Symptom Survey (WURSS-21). Global symptom severity was calculated by the area under the curve (AUC) plotting duration versus WURSS total. Of the specimens tested, 56% were positively identified for one or more of nine different respiratory viruses. During acute respiratory infection illness, both IL-8 and neutrophils positively correlate with AUC (r(s) = 0.082, P = 0.022; r(s)  = 0.080, P = 0.030). IL-8 and neutrophils correlate with nasal symptom severity: runny nose (r = 0.13, P = acute respiratory infection. Further research is necessary to determine if the concentration of these or other biomarkers can predict the overall duration and severity of acute respiratory infection illness. © 2014 Wiley Periodicals, Inc.

Risk modification of colorectal cancer susceptibility by interleukin-8 -251T>A polymorphism in Malaysians.

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Mustapha, Mohd Aminudin; Shahpudin, Siti Nurfatimah Mohd; Aziz, Ahmad Aizat Abdul; Ankathil, Ravindran

2012-06-07

To investigate the allele and genotype frequencies and associated risk of interleukin (IL)-8 -251T>A polymorphism on colorectal cancer (CRC) susceptibility risk. Peripheral blood samples of 255 normal controls and 255 clinically and histopathologically confirmed CRC patients were genotyped for IL-8 -251T>A polymorphism employing allele-specific polymerase chain reaction. The relative association of variant allele and genotypes with CRC susceptibility risk was determined by calculating the odds ratios (ORs). Corresponding χ² tests on the CRC patients and controls were carried out and 95% confidence intervals (CIs) were determined using Fisher's exact test. The allele frequencies and its risk association were calculated using FAMHAP, haplotype association analysis software. On comparing the frequencies of genotypes of patients and controls, the homozygous variant AA was significantly higher in CRC patients (P = 0.002) compared to controls. Investigation on the association of the polymorphic genotypes with CRC susceptibility risk, showed that the homozygous variant IL-8 -251AA had a significantly increased risk with OR 3.600 (95% CI: 1.550-8.481, P = 0.001). In the case of allele frequencies, variant allele A of IL-8 -251 showed a significantly increased risk of CRC predisposition with OR 1.32 (95% CI: 1.03-1.69, P = 0.003). Variant allele and genotype of IL-8 (-251T>A) was significantly associated with CRC susceptibility risk and could be considered as a high-risk variant for CRC predisposition.

Effect of 1.2% of simvastatin gel as a local drug delivery system on Gingival Crevicular Fluid interleukin-6 & interleukin-8 levels in non surgical treatment of chronic periodontitis patients.

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Gunjiganur Vemanaradhya, Gayathri; Emani, Shilpa; Mehta, Dhoom Singh; Bhandari, Shilpy

2017-10-01

The present study was carried out to evaluate the effect of 1.2% simvastatin gel as local drug delivery (LDD) system on Gingival Crevicular Fluid (GCF) Interleukin -6 (IL-6) and Interleukin-8 (IL-8) levels in chronic periodontitis patients, in addition to scaling and root planing (SRP). A total of 46 chronic periodontitis patients were equally divided into two groups. Group I patients were treated by SRP; Group II patients were treated by SRP followed by LDD of 1.2% simvastatin (SMV) gel. Plaque index (PI), Gingival index(GI), Sulcus Bleeding Index (SBI), Probing pocket depth (PPD) and Relative clinical attachment level (CAL) were recorded & GCF samples were collected at baseline (0day) and at 45th day from both the groups. The collected GCF samples were analysed for IL-6 and IL-8 levels with enzyme-linked immunosorbent assay (ELISA). Both the groups showed significant reduction in all the clinical parameters scores and IL-6 and IL-8 levels after non-surgical periodontal therapy (SRP for group I/SRP+1.2% SMV gel for group II) in contrast to baseline values. However, a greater reduction was observed in group II. A non-significant positive correlation was observed between clinical parameters and IL-6 and IL-8 levels except at baseline, a significant correlation was observed between PPD &IL 6 levels in group II. In adjunct to SRP, 1.2% Simvastatin gel acts as an effective local drug delivery agent for the management of chronic periodontitis. Copyright © 2017 Elsevier Ltd. All rights reserved.

The role of serum and urine interleukin-8 on acute pyelonephritis and subsequent renal scarring in children.

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Sheu, Ji-Nan; Chen, Shan-Ming; Meng, Meng-Hsiao; Lue, Ko-Huang

2009-10-01

Interleukin (IL)-8 acts as a potent neutrophils chemoattractant responsible for the migration of neutrophils into the infected renal tissue to protect against invading pathogens. The aim of this study was to assess the role of IL-8 on acute-phase pyelonephritis and later renal scarring in children. A total of 124 children with a first-time febrile urinary tract infection (UTI) were studied. The diagnosis of acute pyelonephritis was confirmed by Tc-dimercaptosuccinic acid (DMSA) renal scan. Serum and urine samples were obtained from 124 children with UTI and 20 healthy children for IL-8 measurement. The 124 children were divided into acute pyelonephritis (n = 70) and lower UTI (n = 54) groups according to the results of DMSA scans. The initial serum and urine IL-8 values of children with acute pyelonephritis were significantly higher when compared with lower UTI and healthy controls (all P or =III all were independent predictors of renal scarring. Those children younger than 2 years of age with the highest IL-8 concentrations during the acute phase of pyelonephritis as well as children with reflux grades of III or greater are at a high-risk for developing renal scarring in the future.

Association of duffy blood group gene polymorphisms with IL8 gene in chronic periodontitis.

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Emília Ângela Sippert

Full Text Available The antigens of the Duffy blood group system (DARC act as a receptor for the interleukin IL-8. IL-8 plays an important role in the pathogenesis of chronic periodontitis due to its chemotactic properties on neutrophils. The aim of this study was to investigate a possible association of Duffy blood group gene polymorphisms with the -353T>A, -845T>C and -738T>A SNPs of the IL8 gene in chronic periodontitis. One hundred and twenty-four individuals with chronic periodontitis and 187 controls were enrolled. DNA was extracted using the salting-out method. The Duffy genotypes and IL8 gene promoter polymorphisms were investigated by PCR-RFLP. Statistical analyses were conducted using the Chi square test with Yates correction or Fisher's Exact Test, and the possibility of associations were evaluated by odds ratio with a 95% confidence interval. When analyzed separately, for the Duffy blood group system, differences in the genotype and allele frequencies were not observed between all the groups analyzed; and, in nonsmokers, the -845C allele (3.6% vs. 0.4%, -845TC genotype (7.3% vs. 0.7% and the CTA haplotype (3.6% vs. 0.4% were positively associated with chronic periodontitis. For the first time to our knowledge, the polymorphisms of erythroid DARC plus IL8 -353T>A SNPs were associated with chronic periodontitis in Brazilian individuals. In Afro-Brazilians patients, the FY*02N.01 with IL8 -353A SNP was associated with protection to chronic periodontitis.

Association of duffy blood group gene polymorphisms with IL8 gene in chronic periodontitis.

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Sippert, Emília Ângela; de Oliveira e Silva, Cléverson; Visentainer, Jeane Eliete Laguila; Sell, Ana Maria

2013-01-01

The antigens of the Duffy blood group system (DARC) act as a receptor for the interleukin IL-8. IL-8 plays an important role in the pathogenesis of chronic periodontitis due to its chemotactic properties on neutrophils. The aim of this study was to investigate a possible association of Duffy blood group gene polymorphisms with the -353T>A, -845T>C and -738T>A SNPs of the IL8 gene in chronic periodontitis. One hundred and twenty-four individuals with chronic periodontitis and 187 controls were enrolled. DNA was extracted using the salting-out method. The Duffy genotypes and IL8 gene promoter polymorphisms were investigated by PCR-RFLP. Statistical analyses were conducted using the Chi square test with Yates correction or Fisher's Exact Test, and the possibility of associations were evaluated by odds ratio with a 95% confidence interval. When analyzed separately, for the Duffy blood group system, differences in the genotype and allele frequencies were not observed between all the groups analyzed; and, in nonsmokers, the -845C allele (3.6% vs. 0.4%), -845TC genotype (7.3% vs. 0.7%) and the CTA haplotype (3.6% vs. 0.4%) were positively associated with chronic periodontitis. For the first time to our knowledge, the polymorphisms of erythroid DARC plus IL8 -353T>A SNPs were associated with chronic periodontitis in Brazilian individuals. In Afro-Brazilians patients, the FY*02N.01 with IL8 -353A SNP was associated with protection to chronic periodontitis.

Interleukin-6, interleukin-8, and soluble tumor necrosis factor receptor-I in the cord blood as predictors of chronic lung disease in premature infants.

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An, Hiromi; Nishimaki, Shigeru; Ohyama, Makiko; Haruki, Atsushi; Naruto, Takuya; Kobayashi, Naoki; Sugai, Toshiyuki; Kobayashi, Yoshinori; Mori, Masaaki; Seki, Kazuo; Yokota, Shumpei

2004-11-01

In order to predict the late-development of chronic lung disease of prematurity (CLD), cytokines in the cord blood were assessed in this study. Eighteen premature infants with CLD were enrolled. Cord blood plasma levels of cytokines of these infants and 12 control infants without CLD were measured including interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, soluble TNF receptor-I, and soluble IL-6 receptor using a cytometric bead array and an enzyme-linked immunosorbent assay. The cord blood IL-6, IL-8, and sTNFR-I levels were significantly elevated in CLD infants compared with those in control (P < .05). IL-1beta, IL-2, IL-4, IL-10, and IFN-gamma were undetectable in both groups. CLD infants with maternal chorioamnionitis had higher IL-6 than those without chorioamnionitis (P < .01). In CLD infants, IL-6 was higher in the infants who required prolonged oxygen therapy (P < .05). Elevated inflammatory cytokines in the cord blood are associated with the progression to CLD.

An in vitro test to screen skin sensitizers using a stable THP-1-derived IL-8 reporter cell line, THP-G8.

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Takahashi, Toshiya; Kimura, Yutaka; Saito, Rumiko; Nakajima, Yoshihiro; Ohmiya, Yoshihiro; Yamasaki, Kenshi; Aiba, Setsuya

2011-12-01

Several studies have suggested that interleukin (IL)-8 can serve as a biomarker for discrimination of skin sensitizers from nonsensitizers. We established a stable THP-1-derived IL-8 reporter cell line, THP-G8, which harbors SLO and SLR luciferase genes under the control of IL-8 and glyceraldehyde 3-phosphate dehydrogenase promoters, respectively. After 6 h treatment with chemicals, normalized SLO luciferase activity (nSLO-LA) was calculated by dividing SLO-LA by SLR-LA, and the fold induction of nSLO-LA (FInSLO-LA) was calculated by dividing nSLO-LA of chemically treated cells by that of nontreated cells. The nSLO-LA of THP-G8 cells increased in response to lipopolysaccharide (LPS) and several sensitizers. The FInSLO-LA in THP-G8 cells induced by LPS or sensitizers positively correlated with their induction of IL-8 messenger RNA in THP-1 cells. The nSLO-LA value of THP-G8 cells was significantly increased (FInSLO-LA ≥ 1.4) by 13 of the 15 sensitizers as well as by 5 of the 7 nonsensitizers. Interestingly, pretreatment with N-acetylcysteine suppressed the increase in FInSLO-LA induced by all sensitizers (inhibition index (II) ≤ 0.8) but did not suppress that induced by most of the nonsensitizers. We then evaluated the performance of this assay using values of FInSLO-LA ≥ 1.4 and II ≤ 0.8 in at least two of three independent experiments as the criteria of a sensitizer, which resulted in test accuracies of 82% for the 22 chemicals used and of 88% for the chemicals proposed by European Center for the Validation of Alternative Methods. This newly developed assay is a candidate replacement for animal tests of skin sensitization because of its accuracy, convenience, and high throughput performance.

Mechanism of subdural effusion evolves into chronic subdural hematoma: IL-8 inducing neutrophil oxidative burst.

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Tao, Zhiqiang; Lin, Yingying; Hu, Maotong; Ding, Shenghong; Li, Jianwei; Qiu, Yongming

2016-01-01

Chronic subdural hematoma (CSDH) is still a mysterious disease. Though great success has been has achieved by neuro-surgery treatment, the origin and development of CSDH remains unknown. Tremendous clinical observations have found the correlation of subdural effusion (SDE) and CSDH. However, systematic elucidation of CSDH's origin and progression is lacking while almost all the current hypothesis only explained partial phenomenon. This hypothesis proposes Interleukin (IL)-8 inducing neutrophil respiratory burst is the crucial impact when SDE evolves into CSDH. IL-8 initially secreted by dural border layer cells, accumulates and the concentration of IL-8 rises in the SDE cavity. Accompanied by the formation of neo-membrane under the dura meninges, IL-8 firstly prompts to establish the neo-vasculature in it, and then attracts lymphocytes aggregation in the neo-membrane. Both the newly recruited lymphocytes and endothelial cells assist the further elevation of local IL-8 concentration. When the IL-8 concentration elevated to a particular level, it attracts neutrophils to the inner wall of neo-vessels and primes them to oxidative burst. Lysosomes and superoxide released by these neutrophils make the fragile neo-capillary became leaky, and subsequently the plasma and blood cells run into SDE. However, as long as the erythrocytes come into the cavity, they shall bind large quantity of IL-8 and decrease IL-8 concentration to a lower level relatively that reduce the neutrophils recruit. When this negative feedback is stagnancy, for example, the SDE space is so large in elder man who is experiencing brain atrophy, the neo-vessels have to release more erythrocytes to bind IL-8, the liquid cavity will expand and the high intracranial pressure symptoms appeared. Our hypothesis holds potential for the proper therapeutic intervention of CSDH. IL-8 antagonist and other anti-inflammation drugs like macrolides antibiotics, glucocorticoid and atorvastatin might be optional to resist

IL-8 is upregulated in cervical cancer tissues and is associated with the proliferation and migration of HeLa cervical cancer cells.

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Jia, Linlin; Li, Fengying; Shao, Mingliang; Zhang, Wei; Zhang, Chunbin; Zhao, Xiaolian; Luan, Haiyan; Qi, Yaling; Zhang, Pengxia; Liang, Lichun; Jia, Xiuyue; Zhang, Kun; Lu, Yan; Yang, Zhe; Zhu, Xiulin; Zhang, Qi; Du, Jiwei; Wang, Weiqun

2018-01-01

Interleukin-8 (IL-8) serves an important function in chronic inflammation and cancer development; however, the underlying molecular mechanism(s) of IL-8 in uterine cervical cancer remains unclear. The present study investigated whether IL-8 and its receptors [IL-8 receptor (IL-8R)A and IL-8RB] contributed to the proliferative and migratory abilities of HeLa cervical cancer cells, and also investigated the potential underlying molecular mechanisms. Results demonstrated that IL-8 and its receptors were detected in HeLa cells, and levels of IL-8RA were significantly increased compared with those of IL-8RB. Furthermore, the level of IL-8 in cervical cancer tissues was significantly increased compared with that in normal uterine cervical tissues, and migratory and proliferative efficiencies of HeLa cells treated with exogenous IL-8 were increased, compared with untreated HeLa cells. In addition, exogenous IL-8 was able to downregulate endocytic adaptor protein (NUMB), and upregulate IL-8RA, IL-8RB and extracellular signal-regulated protein kinases (ERKs) expression levels in HeLa cells. Results suggest that IL-8 and its receptors were associated with the tumorigenesis of uterine cervical cancer, and exogenous IL-8 promotes the carcinogenic potential of HeLa cells by increasing the expression levels of IL-8RA, IL-8RB and ERK, and decreasing the expression level of NUMB.

[Correlation of IL-8 and IL-6 in prostatic fluid with serum prostate-specific antigen level in patients with benign prostatic hyperplasia complicated by prostatitis].

Science.gov (United States)

Ren, Xingfei; Wu, Chunlei; Yu, Qinnan; Zhu, Feng; Liu, Pei; Zhang, Huiqing

2016-01-01

To investigate the correlation of the levels of interleukin-8 (IL-8) and IL-6 in the prostatic fluid with serum levels of serum prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH) complicated by prostatitis. A series of 211 patients undergoing surgery of BPH were divided into BPH group (n=75) and BPH with prostatitis group (n=136) according to the white blood cell count in the prostatic fluid. The clinical and laboratory findings were compared between the two groups, and stepwise regression analysis was used to assess the association of IL-8 and IL-6 with serum PSA level. No significant differences were found in age, BMI, blood pressure, blood glucose, blood lipids, IPSS score, PSA-Ratio, or prostate volume between the two groups (Pprostatitis had significantly increased serum PSA and prostate fluid IL-8 and IL-6 levels compared with those without prostatitis (Pprostatic fluid were all positively correlated with serum PSA level. Prostatitis is an important risk factor for elevated serum PSA level in patients with BPH, and both IL-8 and IL-6 levels in the prostatic fluid are correlated with serum PSA level.

H-2g, a glucose analog of blood group H antigen, mediates monocyte recruitment in vitro and in vivo via IL-8/CXCL8

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Rabquer BJ

2012-09-01

Full Text Available Bradley J Rabquer,1,2 Yong Hou,1 Jeffrey H Ruth,1 Wei Luo,1 Daniel T Eitzman,1 Alisa E Koch,3,1 Mohammad A Amin11University of Michigan Medical School, Department of Internal Medicine, Ann Arbor, MI, USA; 2Albion College, Biology Department, Albion, MI, USA; 3VA Medical Service, Department of Veterans Affairs, Ann Arbor, MI, USAObjective: Monocyte (MN recruitment is an essential inflammatory component of many autoimmune diseases, including rheumatoid arthritis (RA. In this study we investigated the ability of 2-fucosyllactose (H-2g, a glucose analog of blood group H antigen to induce MN migration in vivo and determined if H-2g-induced interleukin-8 (IL-8/CXCL8 plays a role in MN ingress in RA.Methods: Sponge granuloma and intravital microscopy assays were performed to examine H-2g-induced in vivo MN migration and rolling, respectively. MNs were stimulated with H-2g, and the production of IL-8/CXCL8 was assessed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. Lastly, in vitro MN migration assays and an in vivo RA synovial tissue severe combined immunodeficiency mouse model were used to determine the role of IL-8/CXCL8 in H-2g-induced MN migration.Results: In vivo, H-2g induced significantly greater MN migration compared to phosphate buffered saline. Intravital microscopy revealed that H-2g mediates MN migration in vivo by inducing MN rolling. In addition, H-2g induced MN production of IL-8/CXCL8, a process that was dependent on Src kinase. Moreover, we found that H-2g mediated MN migration in vitro, and in vivo migration was inhibited by a neutralizing anti-IL-8/CXCL8 antibody.Conclusion: These findings suggest that H-2g mediates MN recruitment in vitro and in vivo (in part via IL-8/CXCL8.Keywords: inflammation, rheumatoid arthritis, chemokine, migration

IL-8 as antibody therapeutic target in inflammatory diseases

DEFF Research Database (Denmark)

Skov, Lone; Beurskens, Frank J; Zachariae, Claus O C

2008-01-01

IL-8 is a chemokine that has been implicated in a number of inflammatory diseases involving neutrophil activation. HuMab 10F8 is a novel fully human mAb against IL-8, which binds a discontinuous epitope on IL-8 overlapping the receptor binding site, and which effectively neutralizes IL-8-dependen...

Prosthetic radioiodination of interleukin-8 ([123/131I]-IL-8): biological behavior in a mouse infection model

International Nuclear Information System (INIS)

Amartey, J.K.; Esguerra, C.; Al-Otaibi, B.; Al-Jammaz, I.; Al-Qahtani, M.; Parhar, R.S.

2005-01-01

Numerous molecular entities with diverse structures have been radiolabeled and investigated as potential infection and inflammation detection agents. However, none of these molecules have gained the acceptance of gallium citrate or radiolabeled autologous white blood cells. We have radioiodinated interleukin-8 using two different methods and tested the biological behavior of the products in mice. As expected, the direct radioiodinated material displayed extensive in vivo deiodination. The use of pyridine-based prosthetic label yielded a product with better kinetics than the direct radioiodination method and showed a better target to non-target ratio. Nonetheless, this method is not suited for labeling of bioactive peptides such as the title peptide because of the very high specific activity required to prevent cytotoxic effects in a human application

Acidic microenvironments induce lymphangiogenesis and IL-8 production via TRPV1 activation in human lymphatic endothelial cells

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Nakanishi, Masako, E-mail: n-masako@wakayama-med.ac.jp [Department of Pathology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509 (Japan); Morita, Yoshihiro [Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871 (Japan); Department of Oral and Maxillofacial Surgery, Seichokai Hannan Municipal Hospital, Hannan, Osaka 599-0202 (Japan); Hata, Kenji [Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871 (Japan); Muragaki, Yasuteru, E-mail: ymuragak@wakayama-med.ac.jp [Department of Pathology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509 (Japan)

2016-07-15

Local acidosis is one of the characteristic features of the cancer microenvironment. Many reports indicate that acidosis accelerates the proliferation and invasiveness of cancer cells. However, whether acidic conditions affect lymphatic metastasis is currently unknown. In the present study, we focused on the effects of acidosis on lymphatic endothelial cells (LECs) to assess the relationship between acidic microenvironments and lymph node metastasis. We demonstrated that normal human LECs express various acid receptors by immunohistochemistry and reverse transcriptase-polymerase chain reaction (PCR). Acidic stimulation with low pH medium induced morphological changes in LECs to a spindle shape, and significantly promoted cellular growth and tube formation. Moreover, real-time PCR revealed that acidic conditions increased the mRNA expression of interleukin (IL)-8. Acidic stimulation increased IL-8 production in LECs, whereas a selective transient receptor potential vanilloid subtype 1 (TRPV1) antagonist, 5′-iodoresiniferatoxin, decreased IL-8 production. IL-8 accelerated the proliferation of LECs, and inhibition of IL-8 diminished tube formation and cell migration. In addition, phosphorylation of nuclear factor (NF)-κB was induced by acidic conditions, and inhibition of NF-κB activation reduced acid-induced IL-8 expression. These results suggest that acidic microenvironments in tumors induce lymphangiogenesis via TRPV1 activation in LECs, which in turn may promote lymphatic metastasis. - Highlights: • Acidity accelerates the growth, migration, and tube formation of LECs. • Acidic condition induces IL-8 expression in LECs. • IL-8 is critical for the changes of LECs. • IL-8 expression is induced via TRPV1 activation.

Effects of coligand variation on the in vivo characteristics of Tc-99m-labeled interleukin-8 in detection of infection.

NARCIS (Netherlands)

Rennen, H.J.J.M.; Eerd-Vismale, J.E.M. van; Oyen, W.J.G.; Corstens, F.H.M.; Edwards, D.S.; Boerman, O.C.

2002-01-01

In our previous studies, interleukin-8 (IL-8) was labeled with (99m)Tc using hydrazinonicotinamide (HYNIC) as bifunctional coupling agent and tricine as coligand. This preparation showed excellent characteristics for imaging of infection in a rabbit model of soft-tissue infection. In the present

Interleukin-8 and Its Receptors in Human Milk from Mothers of Full-Term and Premature Infants.

Science.gov (United States)

Polat, Adem; Tunc, Turan; Erdem, Galip; Yerebasmaz, Neslihan; Tas, Ahmet; Beken, Serdar; Basbozkurt, Gokalp; Saldir, Mehmet; Zenciroglu, Aysegul; Yaman, Halil

2016-06-01

In addition to its nutritional benefits, human milk also has bioactive elements. Limited immunological functions of newborns are supported and altered by the immunological elements of mother milk. Chemokines are of importance among these immune factors. Interleukin-8 (IL-8) has been demonstrated in mother's milk, and its receptors, CXC chemokine receptors (CXCR)-1 and CXCR-2, were detected on cells, responsible for immunological reactions and mammary glandular cells. The soluble forms of these receptors are yet to be described in human milk. In this study, it was aimed to assess the IL-8 levels and the concentrations of its receptors in colostrum and mature mother's milk in regard to preterm and term delivery. The results of this study indicated a decline in IL-8 levels with the lactation stage, but no difference was observed between term and preterm mother's milk. Regarding the CXCR-1 and CXCR-2, the concentrations of these receptors were similar in both colostrum and mature milk. Furthermore, there was not any significant difference between term and preterm mother's milk. In conclusion, this is the first study to investigate the concentrations of CXCR-1 and CXCR-2 with the levels of IL-8 in colostrum and mature human milk of term and preterm newborns. The alterations in IL-8 levels were similar in some of the studies reported. CXCR-1 and CXCR-2 levels did not demonstrate any significant difference. Further studies are required to investigate the soluble forms of these receptors and their relation to IL-8 with larger cohort.

Urine interleukin-6, interleukin-8 and transforming growth factor β1 in infants with urinary tract infection and asymptomatic bacteriuria

Science.gov (United States)

Krzemień, Grażyna; Turczyn, Agnieszka; Pańczyk-Tomaszewska, Małgorzata

2016-01-01

Introduction Urinary tract infection (UTI) occurs in 1.1% of girls and 1.4% of boys during the first year of life. Asymptomatic bacteriuria (ABU) is usually detected incidentally in 0.9% of girls and 2.5% of boys at this age. The aim of the study was to assess the usefulness of measurement of pro-inflammatory urine interleukin (IL)-6 and IL-8 concentrations and anti-inflammatory transforming growth factor β1 (TGF-β1) level in infants with febrile UTI, non-febrile UTI and ABU. Material and methods A total of 35 children, mean age 6.14 ±3.47 months, were divided into three groups: group I – febrile UTI (n = 13), group II – non-febrile UTI (n = 13) and group III – ABU (n = 9). At the time of enrollment urine IL-6, IL-8, TGF-β1 and serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count (WBC) were measured. Renal ultrasound was performed in all children, 99mTc-dimercaptosuccinic acid scintigraphy (DMSA) and voiding cystourethrography in children with UTI. Results Urine concentrations of IL-6 and IL-8 were significantly higher in febrile UTI compared to those with non-febrile UTI and ABU (p children with febrile UTI compared to those with ABU (p children with UTI. No significant difference in frequency of an abnormal DMSA scan compared to a normal scan was found in groups with febrile and non-febrile UTI. No relations between urine cytokines, systemic inflammatory markers and changes in DMSA scan were observed. The cutoff value for detection of inflammatory changes in the DMSA scan for IL-8 was 120 pg/mg creatinine (Cr) and 40 pg/mg Cr for TGF-β1. Based on this value, the sensitivity for IL-8 was 58.3%, specificity 100% and for TGF-β1 66.7% and 83.7%, respectively. Conclusions We found significant differences in children with febrile UTI and ABU regarding urine IL-6, IL-8 and TGF-β1 levels. Urine cytokines and systemic inflammatory markers do not differentiate between upper and lower UTI in infants. PMID:27833443

In vitro secretion profiles of interleukin (IL-1beta, IL-6, IL-8, IL-10, and TNF alpha after selective infection with Escherichia coli in human fetal membranes

Directory of Open Access Journals (Sweden)

Maida-Claros Rolando

2007-12-01

Full Text Available Abstract Background Chorioamniotic membranes infection is a pathologic condition in which an abnormal secretion of proinflammatory cytokines halts fetal immune tolerance. The aim of the present study was to evaluate the functional response of human chorioamniotic membranes, as well as the individual contribution of the amnion and choriodecidua after stimulation with Escherichia coli, a pathogen associated with preterm labor. Methods Explants of chorioamniotic membranes from 10 women (37–40 weeks of gestation were mounted and cultured in a Transwell system, which allowed us to test the amnion and choriodecidua compartments independently. Escherichia coli (1 × 10 6 CFU/mL was added to either the amniotic or the choriodecidual regions or both; after a 24-h incubation, the secretion of IL-1beta, IL-6, TNFalpha, IL-8, and IL-10 in both compartments was measured using a specific ELISA. Data were analyzed by Kruskal-Wallis one-way analysis of variance. Results After stimulation with Escherichia coli, the choriodecidua compartment showed an increase in the secretion of IL-1beta (21-fold, IL-6 (2-fold, IL-8 (6-fold, and IL-10 (37-fold, regardless of which side of the membrane was stimulated; TNFalpha secretion augmented (22-fold also but only when the stimulus was applied simultaneously to both sides. When the amnion was stimulated directly, the level of IL-1beta (13-fold rose significantly; however, the increase in IL-8 secretion was larger (20-fold, regardless of the primary site of infection. TNFalpha secretion in the amnion compartment rose markedly only when Escherichia coli was simultaneously applied to both sides. Conclusion Selective stimulation of fetal membranes with Escherichia coli results in a differential production of IL-1beta, IL-6, TNFalpha, IL-8, and IL-10. These tissues were less responsive when the amnion side was stimulated. This is in agreement with the hypothesis that the choriodecidua may play a primary role during an ascending

MCPIP-1, Alias Regnase-1, Controls Epithelial Inflammation by Posttranscriptional Regulation of IL-8 Production.

Science.gov (United States)

Dobosz, Ewelina; Wilamowski, Mateusz; Lech, Maciej; Bugara, Beata; Jura, Jolanta; Potempa, Jan; Koziel, Joanna

2016-01-01

Pattern recognition receptors are critical for the detection of invading microorganisms. They activate multiple pathways that lead to the induction of proinflammatory responses and pathogen clearance. The intensity and duration of this immune reaction must be tightly controlled spatially and temporally in every tissue by different negative regulators. We hypothesized that monocyte chemoattractant protein-1-induced protein-1 (MCPIP-1) might play a role in maintaining immune homeostasis in the epithelium both under physiological conditions and upon bacterial infection. To this end, we examined the distribution of the MCPIP-1 transcript and protein in various tissues. The MCPIP-1 protein level was higher in epithelial cells than in myeloid cells. MCPIP-1 exerted RNase activity towards the interleukin (IL)-8 transcript and the lifespan of IL-8 was determined by the presence of the stem-loops/hairpin structures at the 3'UTR region of IL-8 mRNA. Moreover, using fully active, purified recombinant MCPIP-1 protein, we elucidated the mechanism by which MCPIP-1 controls the IL-8 mRNA level. In conclusion, we uncovered a novel IL-8-dependent mechanism via which MCPIP-1 maintains epithelial homeostasis. This study reveals for the first time that MCPIP-1 plays a crucial anti-inflammatory role not only in myeloid cells but also in epithelial cells. © 2016 S. Karger AG, Basel.

Evidence that polymorphonuclear neutrophils infiltrate into the developing corpus luteum and promote angiogenesis with interleukin-8 in the cow

Directory of Open Access Journals (Sweden)

Shimizu Takashi

2011-06-01

Full Text Available Abstract Background After ovulation in the cow, the corpus luteum (CL rapidly develops within a few days with angiogenesis and progesterone production. CL formation resembles an inflammatory response due to the influx of immune cells. Neutrophils play a role in host defense and inflammation, and secrete chemoattractants to stimulate angiogenesis. We therefore hypothesized that neutrophils infiltrate in the developing CL from just after ovulation and may play a role in angiogenesis of the CL. Methods and Results Polymorphonuclear neutrophils (PMN were detected in CL tissue by Pas-staining, and interleukin-8 (IL-8, a neutrophil-specific chemoattractant was measured in supernatant of the CL tissue culture: considerable amounts of PMNs and the high level of IL-8 were observed during the early luteal phase (days 1-4 of the estrous cycle. PMNs and IL-8 were low levels in the mid and late luteal phases, but IL-8 was increased during luteal regression. The PMN migration in vitro was stimulated by the supernatant from the early CL but not from the mid CL, and this activity was inhibited by neutralizing with an anti-IL-8 antibody, indicating the major role of IL-8 in inducing active PMN migration in the early CL. Moreover, IL-8 stimulated proliferation of CL-derived endothelial cells (LECs, and both the supernatant of activated PMNs and IL-8 stimulated formation of capillary-like structures of LECs. Conclusion PMNs migrate into the early CL partially due to its major chemoattractant IL-8 produced at high levels in the CL, and PMNs is a potential regulator of angiogenesis together with IL-8 in developing CL in the cow.

Expression of antimicrobial peptides and interleukin-8 during early stages of inflammation: An experimental gingivitis study.

Science.gov (United States)

Dommisch, H; Staufenbiel, I; Schulze, K; Stiesch, M; Winkel, A; Fimmers, R; Dommisch, J; Jepsen, S; Miosge, N; Adam, K; Eberhard, J

2015-12-01

In the oral cavity, the epithelial surface is constantly exposed to a number of different microorganisms that are organized in a well-structured biofilm. The aim of this study was to monitor gingival expression of antimicrobial peptides (AMPs) and interleukin-8 (IL-8) in an early gingivitis model. Experimental gingivitis was allowed to develop in healthy volunteers (n = 17). Bleeding on probing (BOP%) and gingival crevicular fluid volume (GCF) were assessed at baseline and day 1, 3, 5, 7 and 14. Expression of AMPs (human beta-defensin-2, hBD-2; CC-chemokine ligand 20, CCL20; psoriasin, pso/S100A7) and IL-8 was analyzed by immunohistochemistry in gingival biopsies. In addition, hBD-2 and IL-8 protein expression was monitored in GCF using the ELISA technology. Experimental gingivitis gradually developed with an increase in BOP scores and GCF volume over time. In GCF, elevated concentrations of hBD-2 and IL-8 were monitored at day 1, 5 and 7 (p ≤ 0.0002). Immunohistochemical analysis of gingival sections demonstrated increased staining for hBD-2 at day 3, whereas the CCL20, pso/S100A7, and IL-8 expression was increased at later time points (p gingival inflammation. Differential temporal expression for AMPs may ensure a constant antimicrobial activity against changes in the bacterial composition of the growing dental biofilm. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Increase in interleukin-8 production from circulating neutrophils upon antibiotic therapy in cystic fibrosis patients.

Science.gov (United States)

Montemurro, Pasqualina; Mariggiò, Maria A; Barbuti, Giovanna; Cassano, Amalia; Vincenti, Alessandra; Serio, Gabriella; Guerra, Lorenzo; Diana, Anna; Santostasi, Teresa; Polizzi, Angela; Fumarulo, Ruggiero; Casavola, Valeria; Manca, Antonio; Conese, Massimo

2012-12-01

It is not known whether antibiotic therapy for lung disease in cystic fibrosis (CF) has an influence on circulating polymorphonuclear neutrophil (PMN) function and apoptosis. Blood PMNs were obtained from 14 CF patients before and after antibiotic treatment for an acute exacerbation, and from 10 healthy controls. PMNs were evaluated for production of reactive oxygen species (ROS) by spectrophotometry, of cytokines in the conditioned medium by ELISA, and apoptotic response by cytofluorimetry. ROS and interleukin (IL)-8 were produced at higher levels by CF PMNs pre-therapy than control PMNs under basal conditions. IL-8 levels further increased after therapy. Early apoptotic response was higher in CF PMNs pre-therapy than in control PMNs, and this pattern did not change after antibiotic treatment. Circulating PMNs are primed in CF acute patients. Further studies are needed to consider PMN-produced IL-8 as a biomarker to evaluate response to antibiotic therapy in CF patients. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Effects of methyl gallate and gallic acid on the production of inflammatory mediators interleukin-6 and interleukin-8 by oral epithelial cells stimulated with Fusobacterium nucleatum.

Science.gov (United States)

Kang, Mi-Sun; Jang, Hee-Sook; Oh, Jong-Suk; Yang, Kyu-Ho; Choi, Nam-Ki; Lim, Hoi-Soon; Kim, Seon-Mi

2009-12-01

Interactions between periodontal bacteria and human oral epithelial cells can lead to the activation and expression of a variety of inflammatory mediators in epithelial cells. Fusobacterium nucleatum is a filamentous human pathogen that is strongly associated with periodontal diseases. This study examined the effects of methyl gallate (MG) and gallic acid (GA) on the production of inflammatory mediators, interleukin (IL)-6 and IL-8, by oral epithelial cells stimulated by F. nucleatum. In a real-time reverse transcription-polymerase chain reaction and an enzyme-linked immunosorbent assay, live F. nucleatum induced high levels of gene expression and protein release of IL-6 and IL-8. The effects of MG and GA were examined by treating KB oral epithelial cells with MG and GA and stimulating them with F. nucleatum. MG and GA inhibited significantly the increases in the IL-6 and IL-8 gene and protein levels in a dose-dependent manner. These Compounds also inhibited the growth of F. nucleatum. No visible effects of MG and GA on the adhesion and invasion of KB cells by F. nucleatum were observed. In conclusion, both MG and GA inhibit IL-6 and IL-8 production from F. nucleatum-activated KB cells.

EGFRvIII promotes glioma angiogenesis and growth through the NF-κB, interleukin-8 pathway.

Science.gov (United States)

Bonavia, R; Inda, M M; Vandenberg, S; Cheng, S-Y; Nagane, M; Hadwiger, P; Tan, P; Sah, D W Y; Cavenee, W K; Furnari, F B

2012-09-06

Sustaining a high growth rate requires tumors to exploit resources in their microenvironment. One example of this is the extensive angiogenesis that is a typical feature of high-grade gliomas. Here, we show that expression of the constitutively active mutant epidermal growth factor receptor, ΔEGFR (EGFRvIII, EGFR*, de2-7EGFR) is associated with significantly higher expression levels of the pro-angiogenic factor interleukin (IL)-8 in human glioma specimens and glioma stem cells. Furthermore, the ectopic expression of ΔEGFR in different glioma cell lines caused up to 60-fold increases in the secretion of IL-8. Xenografts of these cells exhibit increased neovascularization, which is not elicited by cells overexpressing wild-type (wt)EGFR or ΔEGFR with an additional kinase domain mutation. Analysis of the regulation of IL-8 by site-directed mutagenesis of its promoter showed that ΔEGFR regulates its expression through the transcription factors nuclear factor (NF)-κB, activator protein 1 (AP-1) and CCAAT/enhancer binding protein (C/EBP). Glioma cells overexpressing ΔEGFR showed constitutive activation and DNA binding of NF-κB, overexpression of c-Jun and activation of its upstream kinase c-Jun N-terminal kinase (JNK) and overexpression of C/EBPβ. Selective pharmacological or genetic targeting of the NF-κB or AP-1 pathways efficiently blocked promoter activity and secretion of IL-8. Moreover, RNA interference-mediated knock-down of either IL-8 or the NF-κB subunit p65, in ΔEGFR-expressing cells attenuated their ability to form tumors and to induce angiogenesis when injected subcutaneously into nude mice. On the contrary, the overexpression of IL-8 in glioma cells lacking ΔEGFR potently enhanced their tumorigenicity and produced highly vascularized tumors, suggesting the importance of this cytokine and its transcription regulators in promoting glioma angiogenesis and tumor growth.

IL-8 dictates glycosaminoglycan binding and stability of IL-18 in cystic fibrosis.

LENUS (Irish Health Repository)

Reeves, Emer P

2010-02-01

Dysregulation of airway inflammation contributes to lung disease in cystic fibrosis (CF). Inflammation is mediated by inflammatory cytokines, including IL-8, which illustrates an increase in biological half-life and proinflammatory activity when bound to glycosaminoglycans (GAGs). The aim of this project was to compare IL-8 and IL-18 for their relative stability, activity, and interaction with GAGs, including chondroitin sulfate, hyaluronic acid, and heparan sulfate, present in high quantities in the lungs of patients with CF. Bronchoalveolar lavage fluid was collected from patients with CF (n = 28), non-CF controls (n = 14), and patients with chronic obstructive pulmonary disease (n = 12). Increased levels of IL-8 and reduced concentrations of IL-18 were detected in bronchial samples obtained from CF individuals. The low level of IL-18 was not a defect in IL-18 production, as the pro- and mature forms of the molecule were expressed and produced by CF epithelial cells and monocytes. There was, however, a marked competition between IL-8 and IL-18 for binding to GAGs. A pronounced loss of IL-18 binding capacity occurred in the presence of IL-8, which displaced IL-18 from these anionic-matrices, rendering the cytokine susceptible to proteolytic degradation by neutrophil elastase. As a biological consequence of IL-18 degradation, reduced levels of IL-2 were secreted by Jurkat T lymphocytes. In conclusion, a novel mechanism has been identified highlighting the potential of IL-8 to determine the fate of other inflammatory molecules, such as IL-18, within the inflammatory milieu of the CF lung.

Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma

International Nuclear Information System (INIS)

Fuchigami, Takao; Kibe, Toshiro; Koyama, Hirofumi; Kishida, Shosei; Iijima, Mikio; Nishizawa, Yoshiaki; Hijioka, Hiroshi; Fujii, Tomomi; Ueda, Masahiro; Nakamura, Norifumi; Kiyono, Tohru; Kishida, Michiko

2014-01-01

Highlights: • We studied the interaction between tumor cells and fibroblasts in ameloblastoma. • AM-3 ameloblastoma cells secreted significantly high IL-1α levels. • IL-1α derived from AM-3 cells promoted IL-6 and IL-8 secretion of fibroblasts. • IL-6 and IL-8 activated the cellular motility and proliferation of AM-3 cells. - Abstract: Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave

Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma

Energy Technology Data Exchange (ETDEWEB)

Fuchigami, Takao [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Kibe, Toshiro [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Koyama, Hirofumi; Kishida, Shosei; Iijima, Mikio [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Nishizawa, Yoshiaki [Kagoshima University Faculty of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Hijioka, Hiroshi; Fujii, Tomomi [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Ueda, Masahiro [Natural Science Centre for Research and Education, Kagoshima University, 1-21-24 Koorimoto, Kagoshima 890-8580 (Japan); Nakamura, Norifumi [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Kiyono, Tohru [Department of Virology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuouku, Tokyo 104-0045 (Japan); Kishida, Michiko, E-mail: kmichiko@m2.kufm.kagoshima-u.ac.jp [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan)

2014-09-05

Highlights: • We studied the interaction between tumor cells and fibroblasts in ameloblastoma. • AM-3 ameloblastoma cells secreted significantly high IL-1α levels. • IL-1α derived from AM-3 cells promoted IL-6 and IL-8 secretion of fibroblasts. • IL-6 and IL-8 activated the cellular motility and proliferation of AM-3 cells. - Abstract: Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave

Prosthetic radioiodination of interleukin-8 ([{sup 123/131}I]-IL-8): biological behavior in a mouse infection model

Energy Technology Data Exchange (ETDEWEB)

Amartey, J.K. [Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, MBC-03, P.O. Box 3354, Riyadh 11211 (Saudi Arabia)]. E-mail: amarty@kfshrc.edu.sa; Esguerra, C. [Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, MBC-03, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Al-Otaibi, B. [Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, MBC-03, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Al-Jammaz, I. [Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, MBC-03, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Al-Qahtani, M. [Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, MBC-03, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Parhar, R.S. [Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, MBC-03, P.O. Box 3354, Riyadh 11211 (Saudi Arabia)

2005-01-01

Numerous molecular entities with diverse structures have been radiolabeled and investigated as potential infection and inflammation detection agents. However, none of these molecules have gained the acceptance of gallium citrate or radiolabeled autologous white blood cells. We have radioiodinated interleukin-8 using two different methods and tested the biological behavior of the products in mice. As expected, the direct radioiodinated material displayed extensive in vivo deiodination. The use of pyridine-based prosthetic label yielded a product with better kinetics than the direct radioiodination method and showed a better target to non-target ratio. Nonetheless, this method is not suited for labeling of bioactive peptides such as the title peptide because of the very high specific activity required to prevent cytotoxic effects in a human application.

HuR/ELAVL1 RNA binding protein modulates interleukin-8 induction by muco-active ribotoxin deoxynivalenol

International Nuclear Information System (INIS)

Choi, Hye Jin; Yang, Hyun; Park, Seong Hwan; Moon, Yuseok

2009-01-01

HuR/Elav-like RNA binding protein 1 (ELAVL1) positively regulates mRNA stability of AU-rich elements (ARE)-containing transcript such as pro-inflammatory cytokines. Ribotoxic stresses can trigger the production of pro-inflammatory mediators by enhancing mRNA stability and the transcriptional activity. We investigated the effects of ribotoxin deoxynivalenol (DON) on HuR translocation and its involvement in the regulation of the pro-inflammatory interleukin-8 (IL-8) mRNA stability. Exposure to the muco-active DON induced nuclear export of both endogenous and exogenous HuR RNA binding protein in human intestinal epithelial cells. Moreover, the interference with HuR protein production suppressed ribotoxic DON-induced IL-8 secretion and its mRNA stability. Cytoplasmic HuR protein interacted with IL-8 mRNA and the complex stabilization was due to the presence of 3'-untranslated region of the transcript. Partly in terms of IL-8-modulating transcription factors, HuR protein was demonstrated to be positively and negatively associated with DON-induced early growth response gene 1 (EGR-1) and activating transcription factor 3 (ATF3), respectively. HuR was a critical mechanistic link between ribotoxic stress and the pro-inflammatory cytokine production, and may have a broader functional significance with regard to mucosal insults since ribotoxic stress responses are also produced upon interactions with the diverse environment of gut.

Identification of NR4A2 as a transcriptional activator of IL-8 expression in human inflammatory arthritis.

LENUS (Irish Health Repository)

Aherne, Carol M

2009-10-01

Expression of the orphan nuclear receptor NR4A2 is controlled by pro-inflammatory mediators, suggesting that NR4A2 may contribute to pathological processes in the inflammatory lesion. This study identifies the chemoattractant protein, interleukin 8 (IL-8\\/CXCL8), as a molecular target of NR4A2 in human inflammatory arthritis and examines the mechanism through which NR4A2 modulates IL-8 expression. In TNF-alpha-activated human synoviocyte cells, enhanced expression of IL-8 mRNA and protein correspond to temporal changes in NR4A2 transcription and nuclear distribution. Ectopic expression of NR4A2 leads to robust changes in endogenous IL-8 mRNA levels and co-treatment with TNF-alpha results in significant (p<0.001) secretion of IL-8 protein. Transcriptional effects of NR4A2 on the human IL-8 promoter are enhanced in the presence of TNF-alpha, suggesting molecular crosstalk between TNF-alpha signalling and NR4A2. A dominant negative IkappaB kinase antagonizes the combined effects of NR4A2 and TNF-alpha on IL-8 promoter activity. Co-expression of NR4A2 and the p65 subunit of NF-kappaB enhances IL-8 transcription and functional studies indicate that transactivation occurs independently of NR4A2 binding to DNA or heterodimerization with additional nuclear receptors. The IL-8 minimal promoter region is sufficient to support NR4A2 and NF-kappaB\\/p65 co-operative activity and NR4A2 can interact with NF-kappaB\\/p65 on a 39bp sequence within this region. In patients treated with methotrexate for active inflammatory arthritis, a reduction in NR4A2 synovial tissue levels correlate significantly (n=10, r=0.73, p=0.002) with changes in IL-8 expression. Collectively, these data delineate an important role for NR4A2 in modulating IL-8 expression and reveal novel transcriptional responses to TNF-alpha in human inflammatory joint disease.

Interleukin-5, interleukin-6, interleukin-8 and tumour necrosis factor-alpha levels obtained within 24-h of admission do not predict high-risk infection in children with febrile neutropenia

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R Aggarwal

2013-01-01

Full Text Available Purpose: Biomarkers that can predict the severity of febrile neutropenia (FN are potential tools for clinical practice. Objective: The objective of this study is to evaluate the reliability of plasma interleukin (IL levels as indicators of high-risk FN. Materials and Methods: Children with haematological malignancies and FN were enrolled prospectively. A blood sample was obtained within 24-h of admission for estimation of IL-5, IL-6, IL-8 and tumour necrosis factor-alpha (TNF-α level by the enzyme-linked immunosorbent assay. Patients were stratified into three groups. Group I (low-risk: No focus of infection; Group II: Clinical/radiological focus of infection; Group III: Microbiologically proven infection or FN related mortality. Groups II and III were analysed as high-risk. The cytokines were assessed at three different cut-off levels. Results: A total of 52 episodes of FN in 48 patients were evaluated. The mean age was 6 years (range: 2-13. Primary diagnosis included acute lymphoblastic leukaemia (82%, non-Hodgkin′s lymphoma (13% and acute myeloid leukaemia (5%. Absolute neutrophil count was < 200 cells/μl in half and 200-500 in 23%. Majority were categorised as Group I (69%, followed by Group II (16% and III (15%. The range of IL-5 was too narrow and similar in the two risk-groups to be of any relevance. The best sensitivity of TNF-α and IL-6 for high-risk group was 78% and 70%, respectively. The highest specificity observed was 35%. The negative predictive value of IL-6, IL-8 and TNF-α exceeded 80%. Conclusion: IL-5, IL-6, IL-8 and TNF-α failed as predictors of clinically localised or microbiologically documented infection in children with chemotherapy induced FN. However, IL-6, IL-8 and TNF-α could be useful in excluding the possibility of high-risk infection.

IL-6 trans-Signaling-Dependent Rapid Development of Cytotoxic CD8+ T Cell Function

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Jan P. Böttcher

2014-09-01

Full Text Available Immune control of infections with viruses or intracellular bacteria relies on cytotoxic CD8+ T cells that use granzyme B (GzmB for elimination of infected cells. During inflammation, mature antigen-presenting dendritic cells instruct naive T cells within lymphoid organs to develop into effector T cells. Here, we report a mechanistically distinct and more rapid process of effector T cell development occurring within 18 hr. Such rapid acquisition of effector T cell function occurred through cross-presenting liver sinusoidal endothelial cells (LSECs in the absence of innate immune stimulation and known costimulatory signaling. Rather, interleukin-6 (IL-6 trans-signaling was required and sufficient for rapid induction of GzmB expression in CD8+ T cells. Such LSEC-stimulated GzmB-expressing CD8+ T cells further responded to inflammatory cytokines, eliciting increased and protracted effector functions. Our findings identify a role for IL-6 trans-signaling in rapid generation of effector function in CD8+ T cells that may be beneficial for vaccination strategies.

Periapical fluid RANKL and IL-8 are differentially regulated in pulpitis and apical periodontitis.

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Rechenberg, Dan-K; Bostanci, Nagihan; Zehnder, Matthias; Belibasakis, Georgios N

2014-09-01

The dental pulp space can become infected due to a breach in the surrounding hard tissues. This leads to inflammation of the pulp (pulpitis), soft tissue breakdown, and finally to bone loss around the root apex (apical periodontitis). The succession of the molecular events leading to apical periodontitis is currently not known. The main inflammatory mediator associated with neutrophil chemotaxis is interleukin-8 (IL-8), and with bone resorption the dyad of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG). The levels of RANKL, OPG and IL-8 were studied in periapical tissue fluid of human teeth (n = 48) diagnosed with symptomatic irreversible pulpitis (SIP) and asymptomatic apical periodontitis (AAP). SIP represents the starting point, and AAP an established steady state of the disease. Periapical tissue fluid samples were collected using paper points and then evaluated using enzyme-linked immunosorbent assays (ELISAs). Target protein levels per case were calibrated against the corresponding total protein content, as determined fluorometrically. RANKL was expressed at significantly higher levels in SIP compared to AAP (P apical periodontitis, periapical bone resorption signaling, as determined by RANKL, occurs prior to inflammatory cell recruitment signaling, as determined by IL-8. Copyright © 2014 Elsevier Ltd. All rights reserved.

Interleukin-9 receptor α chain mRNA formation in CD8+ T cells producing anti-human immunodeficiency virus type 1 substance(s)

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Hossain, M.M.; Tsuchie, H.; Detorio, M.A.; Shirono, H.; Hara, C.; Nishimoto, A.; Saji, A.; Koga, J.; Takata, N.; Maniar, J.K.; Saple, D.G.; Taniguchi, K.; Kageyama, S.; Ichimura, H.; Kurimura, T.

1998-01-01

A search for gene(s) associated with anti-human immunodeficiency virus type 1 (HIV-l) activity of CD8 + T cells was attempted using molecular cloning and the relation between the anti-HIV activity of CD8 + T cells and the interleukin-9 receptor a chain (IL-9R-α) mRNA expression from the cDNA clones obtained was examined. The anti-HIV-l activity of CD8 + T cell culture supernatants was assessed by measuring the level of HIV-l replication in a CD4 + T cell line transfected with an infectious HIV-l DNA clone. IL-9R-a mRNA was assayed by reverse transcriptase-polymerase chain reaction (RT-PCR). Of 5 cases showing high level of anti-HIV-l activity (more than 80% suppression of HIV-l replication), the mRNA was detected in 4 cases. Of 10 cases showing low level of anti-HIV-l activity (less than 80% suppression of HIV-l replication), the mRNA was detected in one case. Soluble recombinant human IL-9 receptor (rhIL-9sR) did not suppress HIV-l replication at a concentration of 1 μg/ml. These data suggest that the IL-9R-a mRNA formation in CD8 + T cells may correlate with and play some role in the anti-HIV-l activity of CD8+ T cells from HIV-l-infected individuals. Key words: CD8+ T cells; anti-HIV-l activity; cytokines; interleukin-9 receptor (authors)

Early serum interleukin-8 evaluation may prove useful in localizing abnormally implanted human gestations after in vitro fertilization.

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Morelli, Sara S; Keegan, Debbra A; Krey, Lewis C; Katz, Joseph; Liu, Mengling; Noyes, Nicole

2008-12-01

To determine whether early measurement of the serum cytokines interleukin-2 receptor (IL-2R), IL-6, and IL-8 along with human chorionic gonadotropin (hCG) and progesterone (P(4)) can differentiate an ectopic from an intrauterine gestation. Retrospective analysis. University-based fertility center. 75 women who underwent treatment with in vitro fertilization (IVF) and subsequently had an ectopic gestation (n = 15), spontaneous abortion (SAB) (n = 30), or term delivery (TD) (n = 30). Serum samples were obtained 14 (day 28) and 21 (day 35) days after oocyte retrieval. Serum concentrations of IL-2R, IL-6, IL-8, P(4), and hCG. Median hCG readings on day 28 and day 35 were statistically significantly lower in the ectopic gestation group than in those with spontaneous abortion or term delivery. On day 28, median IL-8 levels were lower in the ectopic gestation group when compared with all intrauterine gestations combined. No statistically significant differences in IL-2R or IL-6 levels were noted between groups. Despite P(4) supplementation, median day-35 P(4) levels were lower in ectopic gestation than in the spontaneous abortion and term delivery cycles. In the setting of a rise or plateau in hCG levels, low day-28 IL-8 and day-35 P(4) levels suggested an extrauterine implantation. This assay combination may facilitate earlier diagnosis of an ectopic gestation when pregnancy location is unclear.

Prognostic significance of interleukin-8 and CD163-positive cell-infiltration in tumor tissues in patients with oral squamous cell carcinoma.

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Yohei Fujita

Full Text Available PURPOSE: We investigated whether serum interleukin (IL-8 reflects the tumor microenvironment and has prognostic value in patients with oral squamous cell carcinoma (OSCC. EXPERIMENTAL DESIGN: Fifty OSCC patients who received radical resection of their tumor(s were enrolled. Preoperative sera were measured for IL-8 by ELISA. Expression of IL-8 and the infiltration of immune cells in tumor tissues were analyzed by an immunohistochemical staining of surgical specimens. RESULTS: We found that disease-free survival (DFS was significantly longer in the Stage I/II OSCC patients with low serum IL-8 levels compared to those with high levels (p = 0.001. The tumor expression of IL-8, i.e., IL-8(T and the density of CD163-positive cells in the tumor invasive front, i.e., CD163(IF were correlated with the serum IL-8 level (p = 0.033 and p = 0.038, respectively, and they were associated with poor clinical outcome (p = 0.007 and p = 0.002, respectively, in DFS in all patients. A multivariate analysis revealed that N status, IL-8(T and CD163(IF significantly affected the DFS of the patients. Further analysis suggested that combination of N status with serum IL-8, IL-8(T or CD163(IF may be a new criterion for discriminating between OSCC patients at high and low risk for tumor relapse. Interestingly, the in vitro experiments demonstrated that IL-8 enhanced generation of CD163-positive M2 macrophages from peripheral blood monocytes, and that the cells produced IL-10. CONCLUSIONS: These findings indicate that IL-8 may be involved in poor clinical outcomes via generation of CD163-positive M2 macrophages, and that these factors in addition to N status may have prognostic value in patients with resectable OSCSS.

IL-8 signaling is up-regulated in alcoholic hepatitis and DDC fed mice with Mallory Denk Bodies (MDBs) present.

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Liu, Hui; French, Barbara A; Nelson, Tyler J; Li, Jun; Tillman, Brittany; French, Samuel W

2015-10-01

Chemokines and their receptors are involved in oncogenesis and in tumor progression, invasion, and metastasis. Various chemokines also promote cell proliferation and resistance to apoptosis of stressed cells. The chemokine CXCL8, also known as interleukin-8 (IL-8), is a proinflammatory molecule that has functions within the tumor microenvironment. Deregulation of IL-8 signaling is shown to play pivotal roles in tumorigenesis and progression. Mallory-Denk Bodies (MDBs) are prevalent in various liver diseases including alcoholic hepatitis (AH) and are formed in mice livers by feeding DDC. By comparing AH livers where MDBs had formed with normal livers, there were significant changes of IL-8 signaling by RNA sequencing (RNA-Seq) analyses. Real-time PCR analysis of CXCR2 further shows a 6-fold up-regulation in AH livers and a 26-fold up-regulation in the livers of DDC re-fed mice. IL-8 mRNA was also significantly up-regulated in AH livers and DDC re-fed mice livers. This indicates that CXCR2 and IL-8 may be crucial for liver MDB formation. MDB containing balloon hepatocytes in AH livers had increased intensity of staining of the cytoplasm for both CXCR2 and IL-8. Overexpression of IL-8 leads to an increase of the mitogen activated protein kinase (MAPK) cascade and exacerbates the inflammatory cycle. These observations constitute a demonstration of the altered regulation of IL-8 signaling in the livers of AH and mice fed DDC where MDBs formed, providing further insight into the mechanism of MDB formation mediated by IL-8 signaling in AH. Copyright © 2015 Elsevier Inc. All rights reserved.

IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression

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Kiyomiya, Hiroyasu [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Ariyoshi, Wataru; Okinaga, Toshinori [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Kaneuji, Takeshi [Division of Oral Medicine, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Mitsugi, Sho [Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Sakurai, Takuma [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Habu, Manabu [Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Yoshioka, Izumi [Division of Oral Medicine, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Tominaga, Kazuhiro [Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); and others

2015-05-01

Interleukin (IL)-33 is a recently discovered proinflammatory cytokine that belongs to the IL-1 family. Several studies have reported that IL-33 inhibits osteoclast differentiation. However, the mechanism of IL-33 regulation of osteoclastogenesis remains unclear. In the present study, we examined the effect of IL-33 on osteoclast formation in vitro. IL-33 suppressed osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW264.7 cells induced by receptor activator of NF-κB ligand (RANKL) and/or macrophage stimulating factor (M-CSF). IL-33 also inhibited the expression of RANKL-induced nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), thereby decreasing the expression of osteoclastogenesis-related marker genes, including Cathepsin K, Osteoclast stimulatory transmembrane protein (Oc-stamp) and Tartrate-resistant acid phosphatase (Trap). Blockage of IL-33-ST2 binding suppressed the IL-33-mediated inhibition of NFATc1. RANKL-induced B-lymphocyte-induced maturation protein-1 (Blimp-1) expression was also suppressed by IL-33, which was followed by the stimulation of anti-osteoclastic genes such as interferon regulatory factor-8 (IRF-8). These results suggest that IL-33-ST2 interactions down-regulate both RANKL-induced NFATc1 activation and osteoclast differentiation via the regulation of Blimp-1 and IRF-8 expression. - Highlights: • IL-33 inhibits RANKL-induced osteoclast formation. • IL-33 has inhibitory effect on the RANKL-induced NFATc1 expression. • IL-33-induced NFATc1 suppression depends on the regulation of Blimp-1 and IRF-8.

IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression

International Nuclear Information System (INIS)

Kiyomiya, Hiroyasu; Ariyoshi, Wataru; Okinaga, Toshinori; Kaneuji, Takeshi; Mitsugi, Sho; Sakurai, Takuma; Habu, Manabu; Yoshioka, Izumi; Tominaga, Kazuhiro

2015-01-01

Interleukin (IL)-33 is a recently discovered proinflammatory cytokine that belongs to the IL-1 family. Several studies have reported that IL-33 inhibits osteoclast differentiation. However, the mechanism of IL-33 regulation of osteoclastogenesis remains unclear. In the present study, we examined the effect of IL-33 on osteoclast formation in vitro. IL-33 suppressed osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW264.7 cells induced by receptor activator of NF-κB ligand (RANKL) and/or macrophage stimulating factor (M-CSF). IL-33 also inhibited the expression of RANKL-induced nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), thereby decreasing the expression of osteoclastogenesis-related marker genes, including Cathepsin K, Osteoclast stimulatory transmembrane protein (Oc-stamp) and Tartrate-resistant acid phosphatase (Trap). Blockage of IL-33-ST2 binding suppressed the IL-33-mediated inhibition of NFATc1. RANKL-induced B-lymphocyte-induced maturation protein-1 (Blimp-1) expression was also suppressed by IL-33, which was followed by the stimulation of anti-osteoclastic genes such as interferon regulatory factor-8 (IRF-8). These results suggest that IL-33-ST2 interactions down-regulate both RANKL-induced NFATc1 activation and osteoclast differentiation via the regulation of Blimp-1 and IRF-8 expression. - Highlights: • IL-33 inhibits RANKL-induced osteoclast formation. • IL-33 has inhibitory effect on the RANKL-induced NFATc1 expression. • IL-33-induced NFATc1 suppression depends on the regulation of Blimp-1 and IRF-8

RNAi-based therapeutic nanostrategy: IL-8 gene silencing in pancreatic cancer cells using gold nanorods delivery vehicles

International Nuclear Information System (INIS)

Panwar, Nishtha; Yang, Chengbin; Yin, Feng; Chuan, Tjin Swee; Yong, Ken-Tye; Yoon, Ho Sup

2015-01-01

RNA interference (RNAi)-based gene silencing possesses great ability for therapeutic intervention in pancreatic cancer. Among various oncogene mutations, Interleukin-8 (IL-8) gene mutations are found to be overexpressed in many pancreatic cell lines. In this work, we demonstrate IL-8 gene silencing by employing an RNAi-based gene therapy approach and this is achieved by using gold nanorods (AuNRs) for efficient delivery of IL-8 small interfering RNA (siRNA) to the pancreatic cell lines of MiaPaCa-2 and Panc-1. Upon comparing to Panc-1 cells, we found that the dominant expression of the IL-8 gene in MiaPaCa-2 cells resulted in an aggressive behavior towards the processes of cell invasion and metastasis. We have hence investigated the suitability of using AuNRs as novel non-viral nanocarriers for the efficient uptake and delivery of IL-8 siRNA in realizing gene knockdown of both MiaPaCa-2 and Panc-1 cells. Flow cytometry and fluorescence imaging techniques have been applied to confirm transfection and release of IL-8 siRNA. The ratio of AuNRs and siRNA has been optimized and transfection efficiencies as high as 88.40 ± 2.14% have been achieved. Upon successful delivery of IL-8 siRNA into cancer cells, the effects of IL-8 gene knockdown are quantified in terms of gene expression, cell invasion, cell migration and cell apoptosis assays. Statistical comparative studies for both MiaPaCa-2 and Panc-1 cells are presented in this work. IL-8 gene silencing has been demonstrated with knockdown efficiencies of 81.02 ± 10.14% and 75.73 ± 6.41% in MiaPaCa-2 and Panc-1 cells, respectively. Our results are then compared with a commercial transfection reagent, Oligofectamine, serving as positive control. The gene knockdown results illustrate the potential role of AuNRs as non-viral gene delivery vehicles for RNAi-based targeted cancer therapy applications. (paper)

Knockdown of HIF-1α and IL-8 induced apoptosis of hepatocellular carcinoma triggers apoptosis of vascular endothelial cells.

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Choi, Sung Hoon; Park, Jun Yong; Kang, Wonseok; Kim, Seung Up; Kim, Do Young; Ahn, Sang Hoon; Ro, Simon Wonsang; Han, Kwang-Hyub

2016-01-01

A local hypoxic microenvironment is one of the most important characteristics of solid tumors. Hypoxia inducible factor-1α (HIF-1α) and Interleukin-8 (IL-8) activate tumor survival from hypoxic-induced apoptosis in each pathway. This study aimed to evaluate whether knockdown of HIF-1α and IL-8 induced apoptosis of the hepatocellular carcinoma (HCC) and endothelial cell lines. HCC cell lines were infected with adenovirus-expressing shRNA for HIF-1α and IL-8 and maintained under hypoxic conditions (1% O2, 24 h). The expression levels of HIF-1α and both apoptotic and growth factors were examined by real-time quantitative PCR and western blot. We also investigated apoptosis by TUNEL assay (FACS and Immunofluorescence) and measured the concentration of cytochrome C. Inhibition of HIF-1α and IL-8 up-regulated the expression of apoptotic factors while downregulating anti-apoptotic factors simultaneously. Knockdown of HIF-1α and IL-8 increased the concentration of cytochrome C and enhanced DNA fragmentation in HCC cell lines. Moreover, culture supernatant collected from the knockdown of HIF-1α and IL-8 in HCC cell lines induced apoptosis in human umbilical vein endothelial cells under hypoxia, and the expression of variable apoptotic ligand increased from HCC cell lines, time-dependently. These data suggest that adenovirus-mediated knockdown of HIF-1α and IL-8 induced apoptosis in HCC cells and triggered apoptosis of vascular endothelial cells.

Serum interleukin -8 is not a reliable marker for prediction of vesicoureteral reflux in children with febrile urinary tract infection

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Abolfazl Mahyar

2015-12-01

Full Text Available Objective: In view of the side effects of voiding cystourethrography (VCUG, identification of noninvasive markers predicting the presence of vesicoureteral reflux (VUR is important. This study was conducted to determine the predictive value of serum interleukin-8 (IL-8 in diagnosis of VUR in children with first febrile urinary tract infection (UTI. Materials and Methods: Eighty children with first febrile UTI were divided into two groups, with and without VUR, based on the results of VCUG. The sensitivity, specificity, positive and negative predictive value positive and negative likelihood ratio, and accuracy of IL-8 for prediction of VUR were investigated. Results: Of the 80 children with febrile UTI, 30 (37.5% had VUR. There was no significant difference between the children with and without VUR and also between low and high-grade VUR groups in terms of serum concentration of IL-8 (P>0.05. Based on ROC curve, the sensitivity, specificity, likelihood ratio positive, and accuracy of serum IL-8 was lower than those of erythrocyte sedimentation rate and C-reactive protein. Multivariate logistic regression analysis showed significant positive correlation only between erythrocyte sedimentation rate and VUR. Conclusions: This study showed no significant difference between the children with and without VUR in terms of the serum concentration of IL-8. Therefore, it seems that serum IL-8 is not a reliable marker for prediction of VUR.

Interleukins in preeclampsia

International Nuclear Information System (INIS)

Olusi, Samuel O.; Diejomahoh, M.; Omu, A.; Abdulaziz, A.; Prabha, K.; George, S.

2000-01-01

Preeclampsia is a multisystemic disorder of unknown etiology. Recently,endothelial damage has been implicated in its cause. The objective of thisstudy was to determine the role of interleukins in the etiology ofpreeclampsia. 32 primigravidas with preeclampsia but without any clinicalevidence of infection and 32 age-matched primigravidas with uncomplicatednormal pregnancies were investigated. Phlebotomy was performed at 32 weeks ofgestation and blood collected for immunoassay of interleukin-2 (IL-2),interleukin-2 receptor (IL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8)andvinterleukin-10 (IL-10), using commercially available immunoassay kits.Although the maternal plasma concentrations of IL-2 and IL-2R were slightlyhigher in normal pregnant women (76.3+-13.7 pg/mL and 526+-47.1pg/mL,respectively) than in women with preeclampsia (57.8+-1.08 pg/mL and476.9+-3.9pg/mL, respectively), the difference was not statistically significant(P>0.05). However, maternal plasma IL-6 and IL-8 concentrations weresignificantly higher (P<0.05) in normal pregnancy (158.0+-35.4 pg/mL and5163.6+- 800pg/mL, respectively) than in pregnancy complicated withpreeclampsia (60.0+-13.7 pg/mL and 2495.8+-729 pg/mL, respectively). On thepther hand, maternal plasma concentration of IL-10 was significantly higher(P<0.05) in preeclampsia (93.2+-24.1 pg/mL) than in normal pregnancy(31.0+-7.0 pg/mL). It is concluded that the elevated maternal plasma IL-10concentration in preeclampsia may be protective response to maternalimmunorejection. (author)

Effect of trans-chalcone on hepatic IL-8 through the regulation of miR-451 in male rats

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Karimi-Sales Elham

2018-01-01

Full Text Available Objective. Trans-chalcone is a chalcone with hepatoprotective and anti-inflammatory effects. However, the mechanism of these positive effects, especially on miR-451 as an inflammatory regulator, is poorly understood. In this regard, this microRNA (miRNA acts by inhibition of hepatic interleukin-8 (IL-8 production in the liver which is one of the main proinflammatory cytokines. Th is study for the first time examined the effect of trans-chalcone on miR-451/IL-8 pathway. Methods. In present study, 21 male rats were randomly divided into 3 groups (n=7 per each group: control which received solvent (NS, groups 2 (N2T and 3 (N6T, which received transchalcone for 2 and 6 weeks, respectively. Hepatic level of miR-451 was measured by qRT-PCR. Serum levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST as well as hepatic level of IL-8 protein were measured. Results. Trans-chalcone decreased hepatic level of IL-8 protein and serum level of ALT aft er 2 weeks of treatment without significant change in hepatic miR-451. Moreover, it increased hepatic level of miR-451 and reduced hepatic IL-8 as well as AST and ALT aft er 6 weeks. Conclusion. Based on the results of present study, miR-451/IL-8 pathway is a possible mechanism for hepatoprotective action of trans-chalcone in long-term.

Inhibition of NFkappaB activation and IL-8 expression in human bronchial epithelial cells by acrolein.

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Valacchi, Giuseppe; Pagnin, Elisa; Phung, Anh; Nardini, Mirella; Schock, Bettina C; Cross, Carroll E; van der Vliet, Albert

2005-01-01

Lipid oxidation and environmental pollutants are major sources of alpha,beta-unsaturated aldehydes such as acrolein and 4-hydroxynonenal. Acrolein (2-propenal), a major product of organic combustion such as tobacco smoke, represents the most reactive alpha,beta-unsaturated aldehyde, with high reactivity toward nucleophilic targets such as sulfhydryl groups. To investigate how acrolein affects respiratory tract cell activation, we exposed either primary (NHBE) or immortalized human bronchial epithelial cells (HBE1) to 0-25 microM acrolein, and determined effects on basal and tumor necrosis factor-alpha (TNFalpha)-induced production of the chemokine interleukin (IL)-8. Cell exposure to acrolein dose-dependently suppressed IL-8 mRNA levels in HBE1 cells (26, 40, and 79% at 5, 10, and 25 microM acrolein concentrations, respectively) and resulted in corresponding decreases in IL-8 production. Studies of nuclear factor-kappaB (NFkappaB) activation, an essential event in IL-8 production, showed decreased TNFalpha-induced NFkappaB activation by acrolein, illustrated by inhibition of nuclear translocation of NFkappaB and reduced IkappaBalpha degradation. Immunochemical analysis of IkappaB kinase (IKK), a redox-sensitive regulator of NFkappaB activation, indicated direct modification of the IKK beta-subunit by acrolein, suggesting that acrolein may act directly on IKK. In summary, our results demonstrate that acrolein can suppress inflammatory processes in the airways by inhibiting epithelial IL-8 production through direct or indirect inhibitory effects on NFkappaB activation.

Effects of peritoneal fluid from endometriosis patients on interferon-gamma-induced protein-10 (CXCL10) and interleukin-8 (CXCL8) released by neutrophils and CD4+ T cells.

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Kim, Ji-Yeon; Lee, Dong-Hyung; Joo, Jong-Kil; Jin, Jun-O; Wang, Ji-Won; Hong, Young-Seoub; Kwak, Jong-Young; Lee, Kyu-Sup

2009-09-01

Intraperitoneal immuno-inflammatory changes may be associated with the pathogenesis of endometriosis. We evaluated the effects of peritoneal fluid obtained from patients with endometriosis (ePF) on the release of interferon-gamma-induced protein-10 (IP-10/CXCL10) and interleukin-8 (IL-8/CXCL8) by neutrophils, CD4(+) T cells, and monocytes. Neutrophils, CD4(+) T cells, and monocytes were cultured with ePF and the chemokine levels in the supernatants were then measured using enzyme-linked immunosorbent assay. The addition of ePF to cultures of CD4(+) T cells led to a significant increase in the release of IP-10 when compared with control PF without endometriosis (cPF). There was a positive correlation between the levels of IL-8 and IP-10 in ePF (R = 0.89, P = 0.041), but not between the levels of IP-10 and IL-8 released by neutrophils, CD4(+) T cells, and monocytes. The levels of IP-10 in ePF were positively correlated with the release of IP-10 by ePF-treated neutrophils (R = 0.89, P ePF significantly enhanced the interferon-gamma-induced release of IP-10 by nuetrophils and CD4(+) T cells. These findings suggest that neutrophils and T cells release differential levels of IP-10 and IL-8 in response to stimulation with ePF, and that these cells are a major source of IP-10 in the PF of endometriosis patients.

Hypo-responsiveness of interleukin-8 production in human embryonic epithelial intestine 407 cells independent of NF-κB pathway: New lessons from endotoxin and ribotoxic deoxynivalenol

International Nuclear Information System (INIS)

Moon, Yuseok; Yang, Hyun; Park, Seung-Hwan

2008-01-01

Mucosal epithelium senses external toxic insults and transmits the danger signals into the epithelial cells in order to activate a broad range of inflammatory responses. However, pre-exposure to the commensal endotoxins can induce inflammatory tolerance and maintain the homeostasis without excessive immune responses. We recently reported that ribotoxin deoxynivalenol (DON) and its derivatives elicited the pro-inflammatory response as the mucosal insults in human epithelial cells. Taking the knowledge into consideration, we tested the hypothesis that endotoxin pre-exposure can attenuate ribotoxin-induced epithelial interleukin-8 (IL-8) production via a tolerance mechanism. Pre-exposure to endotoxin repressed IL-8 release and its gene expression. However, inflammatory tolerance was not mediated by the attenuated NF-κB activation which has been generally recognized as the major mediator of LPS-mediated toll-like receptor (TLR) signaling pathway. Instead, pre-exposure to endotoxin was observed to trigger the delayed induction of peroxisome proliferator-activated receptor gamma (PPAR-γ) which contributed to the diminished IL-8 production in the human epithelial cells. Moreover, endogenous PPAR-γ agonist suppressed toxicant-mediated interleukin-8 production and IL-8 mRNA stability. Taken together, endotoxin induced hypo-production of pro-inflammatory cytokine IL-8 in the human epithelial cells, which was associated with the delayed activation of PPAR-γ expression by pre-existing endotoxin

The changes of IL-8, IL-10, IL-12 and IgE in serum of patients with asthma

International Nuclear Information System (INIS)

Zhang Chao; Liu Deyi; Hou Guihua; Wang Haodan

2002-01-01

To evaluate the relationship and the clinical significance between the serum IL-8, IL-10, IL-12 and IgE in patients with asthma, the serum IL-8, IL-10 are measured by radioimmunoassay method and the serum IL-12, IgE by ELISA in 55 patients with asthma. The level of serum IL-8, IgE at stage of episode are significantly higher than that at stage of remission (P<0.01); the level of serum IL-10, IL-12 at stage of episode are significantly lower than that at stage of remission (P<0.01). Linear regression shows that the decrease of IL-12 relate to the increase of IgE. The results suggests that the change of the level of serum IL-8, IL-10, IL-12 and IgE could be a maker for the aggravation of asthma

Increased circulating interleukin-8 in patients with resistance to thyroid hormone receptor α

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Anne H van der Spek

2017-11-01

Full Text Available Innate immune cells have recently been identified as novel thyroid hormone (TH target cells in which intracellular TH levels appear to play an important functional role. The possible involvement of TH receptor alpha (TRα, which is the predominant TR in these cells, has not been studied to date. Studies in TRα0/0 mice suggest a role for this receptor in innate immune function. The aim of this study was to determine whether TRα affects the human innate immune response. We assessed circulating interleukin-8 concentrations in a cohort of 8 patients with resistance to TH due to a mutation of TRα (RTHα and compared these results to healthy controls. In addition, we measured neutrophil and macrophage function in one of these RTHα patients (mutation D211G. Circulating interleukin-8 levels were elevated in 7 out of 8 RTHα patients compared to controls. These patients harbor different mutations, suggesting that this is a general feature of the syndrome of RTHα. Neutrophil spontaneous apoptosis, bacterial killing, NAPDH oxidase activity and chemotaxis were unaltered in cells derived from the RTHαD211G patient. RTHα macrophage phagocytosis and cytokine induction after LPS treatment were similar to results from control cells. The D211G mutation did not result in clinically relevant impairment of neutrophil or pro-inflammatory macrophage function. As elevated circulating IL-8 is also observed in hyperthyroidism, this observation could be due to the high-normal to high levels of circulating T3 found in patients with RTHα.

Salmon trypsin stimulates the expression of interleukin-8 via protease-activated receptor-2

International Nuclear Information System (INIS)

Larsen, Anett K.; Seternes, Ole-Morten; Larsen, Merethe; Aasmoe, Lisbeth; Bang, Berit

2008-01-01

In this study, we focus on salmon trypsin as an activator of inflammatory responses in airway cells in vitro. The rationale behind the investigation is that salmon industry workers are exposed to aerosols containing enzymes, which are generated during industrial processing of the fish. Knowing that serine proteases such as trypsin are highly active mediators with diverse biological activities, the stimulation of nuclear factor-kappa B (NF-κB) and interleukin (IL)-8 and the role of protease-activated receptors (PAR) in inflammatory signal mediation were investigated. Protease-activated receptors are considered important under pathological situations in the human airways, and a thorough understanding of PAR-induced cellular events and their consequences in airway inflammation is necessary. Human airway epithelial cells (A549) were exposed to trypsin isolated from fish (Salmo salar), and we observed that purified salmon trypsin could generate secretion of IL-8 in a concentration-dependent manner. Furthermore, we demonstrate that PAR-2 activation by salmon trypsin is coupled to an induction of NF-κB-mediated transcription using a PAR-2 transfected HeLa cell model. Finally, we show that the release of IL-8 from A549 following stimulation with purified salmon trypsin is mediated through activation of PAR-2 using specific small interfering RNAs (siRNAs). The results presented suggest that salmon trypsin, via activation of PAR-2, might influence inflammation processes in the airways if inhaled in sufficient amounts

The major surface glycoprotein of Pneumocystis carinii induces release and gene expression of interleukin-8 and tumor necrosis factor alpha in monocytes

DEFF Research Database (Denmark)

Benfield, T L; Lundgren, Bettina; Levine, S J

1997-01-01

Recent studies suggest that interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-alpha) may play a central role in host defense and pathogenesis during Pneumocystis carinii pneumonia. In order to investigate whether the major surface antigen (MSG) of human P. carinii is capable of eliciting...... the release of IL-8 and TNF-alpha, human monocytes were cultured in the presence of purified MSG. MSG-stimulated cells released significant amounts of IL-8 within 4 h, and at 20 h, cells stimulated with MSG released 45.5 +/- 9.3 ng of IL-8/ml versus 3.7 +/- 1.1 ng/ml for control cultures (P = 0.......01). In a similar fashion, MSG elicited release of TNF-alpha. Initial increases were also seen at 4 h, and at 20 h, TNF-alpha levels reached 6.4 +/- 1.1 ng/ml, compared to 0.08 +/- 0.01 ng/ml for control cultures (P alpha secretion was observed at 20 h...

СHARACTERISTICS OF THE HEART FATTY ACID-BINDING PROTEIN, INTERLEUKIN-6 AND INTERLEUKIN-8 AS ALTERNATIVE MARKERS OF DIABETIC NEPHROPATHY PROGRESSION IN PATIENTS WITH TYPE 1 DIABETES MELLITUS

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Yu. A. Ryzhikova

2015-01-01

Full Text Available The aim of this work was to study the levels of the heart fatty acid-binding protein (h-FABP, interleukin6 (IL-6 and interleukin-8 (IL-8, in diabetic nephropathy (DN in patients with type 1 diabetes mellitus (T1DM. Material and methods. We examined 87 patients aged 18 to 54 with T1DM within the study group. 30 patients with type 1 diabetes were diagnosed with normoalbuminuria, 29 patients – with microalbuminuria and 28 patients – with proteinuria. The control group consisted of 24 healthy donor aged 22 to 29. The comparison group included 22 patients aged 20 to 42 with verified diagnosis of essential arterial hypertension (AH without carbohydrate metabolism disorders. The daily urinary albumin excretion was determined by immunoturbidimetric technique. 30 patients with type 1 diabetes were diagnosed with normoalbuminuria, 29 patients – with microalbuminuria and 28 patients with proteinuria.Calculation of glomerular filtration rate was performed according to the Hoek formula with the use of cystatinС serum concentrations. Contents of h-FABP, IL-6 and cystatin C in serum and h-FABP, IL-8 inurine were determined by enzyme-linked immunosorbent assay. Results. Analysis of the h-FABP content in serum showed that the concentration of this marker in individuals with T1DM was higher than in patients of the control group and the comparison group. Analysis of the h-FABP content in the urine revealed that individuals with essential hypertension showed an increased level of h-FABP while patients with T1DM demonstrated the highest concentration of h-FABP. The concentration of IL-6 inindividuals with T1DM and in individuals with AH significantly exceeded the control values. The contents of h-FABP and IL-6 inserum and h-FABP and IL-8 inurine increased with the progression of DN and reached maximum in individuals of the proteinuria subgroup. At the same time, the levels of h-FABP and IL-8 inthe urine of patients in the microalbuminuria (MAU subgroup were

Entamoeba histolytica-secreted cysteine proteases induce IL-8 production in human mast cells via a PAR2-independent mechanism.

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Lee, Young Ah; Nam, Young Hee; Min, Arim; Kim, Kyeong Ah; Nozaki, Tomoyoshi; Saito-Nakano, Yumiko; Mirelman, David; Shin, Myeong Heon

2014-01-01

Entamoeba histolytica is an extracellular tissue parasite causing colitis and occasional liver abscess in humans. E. histolytica-derived secretory products (SPs) contain large amounts of cysteine proteases (CPs), one of the important amoebic virulence factors. Although tissue-residing mast cells play an important role in the mucosal inflammatory response to this pathogen, it is not known whether the SPs induce mast cell activation. In this study, when human mast cells (HMC-1 cells) were stimulated with SPs collected from pathogenic wild-type amoebae, interleukin IL-8 mRNA expression and production were significantly increased compared with cells incubated with medium alone. Inhibition of CP activity in the SPs with heat or the CP inhibitor E64 resulted in significant reduction of IL-8 production. Moreover, SPs obtained from inhibitors of cysteine protease (ICP)-overexpressing amoebae with low CP activity showed weaker stimulatory effects on IL-8 production than the wild-type control. Preincubation of HMC-1 cells with antibodies to human protease-activated receptor 2 (PAR2) did not affect the SP-induced IL-8 production. These results suggest that cysteine proteases in E. histolytica-derived secretory products stimulate mast cells to produce IL-8 via a PAR2-independent mechanism, which contributes to IL-8-mediated tissue inflammatory responses during the early phase of human amoebiasis. © Y.A. Lee et al., published by EDP Sciences, 2014.

Entamoeba histolytica-secreted cysteine proteases induce IL-8 production in human mast cells via a PAR2-independent mechanism

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Lee Young Ah

2014-01-01

Full Text Available Entamoeba histolytica is an extracellular tissue parasite causing colitis and occasional liver abscess in humans. E. histolytica-derived secretory products (SPs contain large amounts of cysteine proteases (CPs, one of the important amoebic virulence factors. Although tissue-residing mast cells play an important role in the mucosal inflammatory response to this pathogen, it is not known whether the SPs induce mast cell activation. In this study, when human mast cells (HMC-1 cells were stimulated with SPs collected from pathogenic wild-type amoebae, interleukin IL-8 mRNA expression and production were significantly increased compared with cells incubated with medium alone. Inhibition of CP activity in the SPs with heat or the CP inhibitor E64 resulted in significant reduction of IL-8 production. Moreover, SPs obtained from inhibitors of cysteine protease (ICP-overexpressing amoebae with low CP activity showed weaker stimulatory effects on IL-8 production than the wild-type control. Preincubation of HMC-1 cells with antibodies to human protease-activated receptor 2 (PAR2 did not affect the SP-induced IL-8 production. These results suggest that cysteine proteases in E. histolytica-derived secretory products stimulate mast cells to produce IL-8 via a PAR2-independent mechanism, which contributes to IL-8-mediated tissue inflammatory responses during the early phase of human amoebiasis.

Vitiligo inducing phenols activate the unfolded protein response in melanocytes resulting in upregulation of IL6 and IL8

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Toosi, Siavash; Orlow, Seth J.; Manga, Prashiela

2012-01-01

Vitiligo is characterized by depigmented skin patches due to loss of epidermal melanocytes. Oxidative stress may play a role in vitiligo onset, while autoimmunity contributes to disease progression. In this study we sought to identify mechanisms that link disease triggers and spreading of lesions. A hallmark of melanocytes at the periphery of vitiligo lesions is dilation of the endoplasmic reticulum (ER). We hypothesized that oxidative stress results in redox disruptions that extend to the ER, causing accumulation of misfolded peptides, which activates the unfolded protein response (UPR). We used 4-tertiary butyl phenol (4-TBP) and monobenzyl ether of hydroquinone (MBEH), known triggers of vitiligo. We show that expression of key UPR components, including the transcription factor X-box binding protein 1 (XBP1), are increased following exposure of melanocytes to phenols. XBP1 activation increases production of immune mediators interleukin-6 (IL6) and IL8. Co-treatment with XBP1 inhibitors reduced IL6 and IL8 production induced by phenols, while over-expression of XBP1 alone increased their expression. Thus, melanocytes themselves produce cytokines associated with activation of an immune response following exposure to chemical triggers of vitiligo. These results expand our understanding of the mechanisms underlying melanocyte loss in vitiligo and pathways linking environmental stressors and autoimmunity. PMID:22696056

Effect of intravenous lidocaine combined with amitriptyline on pain intensity, clinical manifestations and the concentrations of IL-1, IL-6 and IL-8 in patients with fibromyalgia: A randomized double-blind study.

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Albertoni Giraldes, Ana Laura; Salomão, Reinaldo; Leal, Plinio da Cunha; Brunialti, Milena Karina Coló; Sakata, Rioko Kimiko

2016-10-01

Regarding the use of intravenous lidocaine in fibromyalgia, there are no well-controlled studies. This study aimed to evaluate the effect of intravenous lidocaine on pain intensity, clinical manifestations and plasma levels of interleukin (IL)-1, IL-6, and IL-8 in fibromyalgia patients. In a randomized double-blind study, group 1 patients received 240 mg of lidocaine in 125 mL of saline solution, while group 2 patients received 125 mL of saline, both once a week for 4 weeks (T1, T2, T3 and T4). All patients received amitriptyline. The following were assessed: pain intensity before treatment (T0) and at 1, 2, 3, 4 and 8 weeks after treatment; clinical manifestations; the fibromyalgia impact questionnaire (FIQ) before and at 4 and 8 weeks after; the levels of IL 1, 6 and 8 before and at 4 and 8 weeks after treatment. Lower pain intensity was observed in the lidocaine group at T2, with no difference at the other time points. There was a reduction in pain intensity in both groups. The use of paracetamol and tramadol and plasma levels of IL-1, IL-6 and IL-8 did not differ between the groups. Clinical manifestations and side effects did not differ between groups. The combination of 240 mg of intravenous lidocaine (once a week for 4 weeks) with 25 mg of amitriptyline for 8 weeks had no meaningful impact in fibromyalgia patients. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

IL8-CXCR2 pathway inhibition as a therapeutic strategy against MDS and AML stem cells.

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Schinke, Carolina; Giricz, Orsolya; Li, Weijuan; Shastri, Aditi; Gordon, Shanisha; Barreyro, Laura; Barreryo, Laura; Bhagat, Tushar; Bhattacharyya, Sanchari; Ramachandra, Nandini; Bartenstein, Matthias; Pellagatti, Andrea; Boultwood, Jacqueline; Wickrema, Amittha; Yu, Yiting; Will, Britta; Wei, Sheng; Steidl, Ulrich; Verma, Amit

2015-05-14

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are associated with disease-initiating stem cells that are not eliminated by conventional therapies. Novel therapeutic targets against preleukemic stem cells need to be identified for potentially curative strategies. We conducted parallel transcriptional analysis of highly fractionated stem and progenitor populations in MDS, AML, and control samples and found interleukin 8 (IL8) to be consistently overexpressed in patient samples. The receptor for IL8, CXCR2, was also significantly increased in MDS CD34(+) cells from a large clinical cohort and was predictive of increased transfusion dependence. High CXCR2 expression was also an adverse prognostic factor in The Cancer Genome Atlas AML cohort, further pointing to the critical role of the IL8-CXCR2 axis in AML/MDS. Functionally, CXCR2 inhibition by knockdown and pharmacologic approaches led to a significant reduction in proliferation in several leukemic cell lines and primary MDS/AML samples via induction of G0/G1 cell cycle arrest. Importantly, inhibition of CXCR2 selectively inhibited immature hematopoietic stem cells from MDS/AML samples without an effect on healthy controls. CXCR2 knockdown also impaired leukemic growth in vivo. Together, these studies demonstrate that the IL8 receptor CXCR2 is an adverse prognostic factor in MDS/AML and is a potential therapeutic target against immature leukemic stem cell-enriched cell fractions in MDS and AML. © 2015 by The American Society of Hematology.

Urinary albumin and interleukin-8 levels are not good indicators of ongoing vesicoureteral reflux in children who have no active urinary tract infection.

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Badeli, Hamidreza; khoshnevis, Termeh; Hassanzadeh Rad, Afagh; Sadeghi, Mehrdad

2013-01-01

Vesicoureteral reflux (VUR) is a risk factor for kidney scarring, hypertension and declining renal function. Standard diagnostic methods are invasive and can cause exposure to radiation and urinary tract infections (UTIs). We aimed to investigate urine albumin and interleukin-8 levels as markers of ongoing VUR and renal damage in children without UTIs. Random urine samples were collected from 51 children, including 16 children with VUR (group A), 17 children with resolved VUR (group B) and 18 normal children (group C). The diagnosis of VUR or resolved VUR was confirmed by voiding cystourethrogram (VCUG) or direct radionuclide cystography (DRNC). All children had normal kidney function and had no evidence of UTI in the preceding three months. Random urine specimens were assayed for albumin (Alb), creatinine (Cr) and interleukin-8 (IL-8) and mean values were compared by one way ANOVA. In groups A and B, the mean age at first UTI was 31.7 ± 2.4 and 27 ± 2.0 months respectively. In group A, the mean duration between VUR diagnosis and study entrance was 30 ± 9.1 months. In group B, the mean duration between VUR diagnosis and recovery was 19.9 ± 1.3 months. Overall, 76.4% of affected children had bilateral VUR and 41.2% had severe VUR. There were no significant differences in urinary Alb, IL-8, Alb/Cr and IL-8/Cr between the three groups. The current study does not support the hypothesis that microalbuminuria or urinary IL-8 are good indicators of ongoing VUR and renal injury in children.

A Soft Coral Natural Product, 11-Episinulariolide Acetate, Inhibits Gene Expression of Cyclooxygenase-2 and Interleukin-8 through Attenuation of Calcium Signaling

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Wei-Chiao Chang

2013-06-01

Full Text Available Epidermal growth factor receptor (EGFR is overexpressed in many types of cancer cells. EGFR-mediated signaling involves inflammatory gene expression including cyclooxygenase (COX-2 and interleukin (IL-8, and is associated with cancer pathogenesis. In a search of phytochemicals with anti-inflammatory activity, the COX-2 and IL-8 inhibitory activities of some marine compounds were examined. After screening these compounds 11-episinulariolide acetate (1 from soft coral exhibited the most potent activity. Reverse-transcription PCR; western blotting; ELISA and luciferase assays were used to test the effect of compound 1 on EGF-stimulated expressions of COX-2 and IL-8 in A431 human epidermoid carcinoma cells. After exposure to 10 μM of compound 1, expression levels of COX-2 and IL-8 were reduced. In addition; intracellular Ca2+ increase and Ca2+-dependent transcription factor activation were blocked by compound 1. Thus, compound 1 can potentially serve as a lead compound for targeting Ca2+ signaling-dependent inflammatory diseases.

Prostaglandin E2 produced by Entamoeba histolytica binds to EP4 receptors and stimulates interleukin-8 production in human colonic cells.

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Dey, Indranil; Chadee, Kris

2008-11-01

Entamoeba histolytica pathogenesis in the colon occurs in a stepwise fashion. It begins with colonization of the mucin layer, which is followed by stimulation of a proinflammatory response that causes nonspecific tissue damage that may facilitate parasite invasion of the underlying colonic mucosa. Unfortunately, the parasite and/or host factors that stimulate a proinflammatory response in the gut are poorly understood. In this study, we found that live E. histolytica or secretory or proteins (SP) and soluble ameba components (SAP) can markedly increase interleukin-8 (IL-8) mRNA expression and protein production in colonic epithelial cells. The IL-8-stimulating molecule produced by live amebae was identified as prostaglandin E(2) (PGE(2)) as trophozoites treated with cyclooxygenase inhibitors inhibited the biosynthesis of PGE(2) and eliminated IL-8 production induced by live parasites or ameba components. Moreover, using specific prostaglandin EP2 and EP4 receptor agonists and antagonists, we found that PGE(2) binds exclusively through EP4 receptors in colonic epithelial cells to stimulate IL-8 production. Silencing of EP4 receptors with EP4 small interfering RNA completely eliminated SP- and SAP-induced IL-8 production. These studies identified bioactive PGE(2) as a one of the major virulence factors produced by E. histolytica that can stimulate the potent neutrophil chemokine and activator IL-8, which can trigger an acute host inflammatory response. Thus, the induction of IL-8 production in response to E. histolytica-derived PGE(2) may be a mechanism that explains the initiation and amplification of acute inflammation associated with intestinal amebiasis.

Activated endothelial interleukin-1beta, -6, and -8 concentrations and intercellular adhesion molecule-1 expression are attenuated by lidocaine.

LENUS (Irish Health Repository)

Lan, Wei

2012-02-03

Endothelial cells play a key role in ischemia reperfusion injury. We investigated the effects of lidocaine on activated human umbilical vein endothelial cell (HUVEC) interleukin (IL)-1beta, IL-6, and IL-8 concentrations and intercellular adhesion molecule-1 (ICAM-1) expression. HUVECs were pretreated with different concentrations of lidocaine (0 to 0.5 mg\\/mL) for 60 min, thereafter tumor necrosis factor-alpha was added at a concentration of 2.5 ng\\/mL and the cells incubated for 4 h. Supernatants were harvested, and cytokine concentrations were analyzed by enzyme-linked immunosorbent assay. Endothelial ICAM-1 expression was analyzed by using flow cytometry. Differences were assessed using analysis of variance and post hoc unpaired Student\\'s t-test where appropriate. Lidocaine (0.5 mg\\/mL) decreased IL-1beta (1.89 +\\/- 0.11 versus 4.16 +\\/- 1.27 pg\\/mL; P = 0.009), IL-6 (65.5 +\\/- 5.14 versus 162 +\\/- 11.5 pg\\/mL; P < 0.001), and IL-8 (3869 +\\/- 785 versus 14,961 +\\/- 406 pg\\/mL; P < 0.001) concentrations compared with the control. IL-1beta, IL-6, and IL-8 concentrations in HUVECs treated with clinically relevant plasma concentrations of lidocaine (0.005 mg\\/mL) were similar to control. ICAM-1 expression on lidocaine-treated (0.05 mg\\/mL) HUVECs was less than on controls (198 +\\/- 52.7 versus 298 +\\/- 50.3; Mean Channel Fluorescence; P < 0.001). Activated endothelial IL-1beta, IL-6, and IL-8 concentrations and ICAM-1 expression are attenuated only by lidocaine at concentrations larger than clinically relevant concentrations.

Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-κB in immortalized and malignant oral keratinocytes

International Nuclear Information System (INIS)

Lee, Hwa-Jeong; Lee, Jun; Lee, Sun-Kyung; Lee, Suk-Keun; Kim, Eun-Cheol

2007-01-01

Interleukin-8 (IL-8) is a cytokine that plays an important role in tumor progression in a variety of cancer types; however, its regulation is not well understood in oral cancer cells. In the present study, we examined the expression and mechanism of IL-8 in which it is involved by treating immortalized (IHOK) and malignant human oral keratinocytes (HN12) cells with deferoxamine (DFO). IL-8 production was measured by an enzyme-linked immunoabsorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Electrophoretic mobility shift assays was used to determine NF-κB binding activity. Phosphorylation and degradation of the I-κB were analyized by Western blot. IHOK cells incubated with DFO showed increased expression of IL-8 mRNA, as well as higher release of the IL-8 protein. The up-regulation of DFO-induced IL-8 expression was higher in IHOK cells than in HN12 cells and was concentration-dependent. DFO acted additively with IL-1β to strongly up-regulate IL-8 in IHOK cells but not in HN12 cells. Accordingly, selective p38 and ERK1/2 inhibitors for both kinases abolished DFO-induced IL-8 expression in both IHOK and HN12 cells. Furthermore, DFO induced the degradation and phosphorylation of IκB, and activation of NF-κB. The IL-8 inducing effects of DFO were mediated by a nitric oxide donor (S-nitrosoglutathione), and by pyrrolidine dithiocarbamate, an inhibitor of NF-κB, as well as by wortmannin, which inhibits the phosphatidylinositol 3-kinase-dependent activation of NAD(P)H oxidase. This results demonstrate that DFO-induced IL-8 acts via multiple signaling pathways in immortalized and malignant oral keratinocytes, and that the control of IL-8 may be an important target for immunotheraphy against human oral premalignant lesions

Hyper-IL-15 suppresses metastatic and autochthonous liver cancer by promoting tumour-specific CD8+ T cell responses.

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Cheng, Liang; Du, Xuexiang; Wang, Zheng; Ju, Jianqi; Jia, Mingming; Huang, Qibin; Xing, Qiao; Xu, Meng; Tan, Yi; Liu, Mingyue; Du, Peishuang; Su, Lishan; Wang, Shengdian

2014-12-01

Liver cancer has a very dismal prognosis due to lack of effective therapy. Here, we studied the therapeutic effects of hyper-interleukin15 (hyper-IL-15), which is composed of IL-15 and the sushi domain of the IL-15 receptor α chain, on metastatic and autochthonous liver cancers. Liver metastatic tumour models were established by intraportally injecting syngeneic mice with murine CT26 colon carcinoma cells or B16-OVA melanoma cells. Primary hepatocellular carcinoma (HCC) was induced by diethylnitrosamine (DEN). A hydrodynamics-based gene delivery method was used to achieve sustained hyper-IL-15 expression in the liver. Liver gene delivery of hyper-IL-15 robustly expanded CD8(+) T and NK cells, leading to a long-term (more than 40 days) accumulation of CD8(+) T cells in vivo, especially in the liver. Hyper-IL-15 treatment exerted remarkable therapeutic effects on well-established liver metastatic tumours and even on DEN-induced autochthonous HCC, and these effects were abolished by depletion of CD8(+) T cells but not NK cells. Hyper-IL-15 triggered IL-12 and interferon-γ production and reduced the expression of co-inhibitory molecules on dendritic cells in the liver. Adoptive transfer of T cell receptor (TCR) transgenic OT-1 cells showed that hyper-IL-15 preferentially expanded tumour-specific CD8(+) T cells and promoted their interferon-γ synthesis and cytotoxicity. Liver delivery of hyper-IL-15 provides an effective therapy against well-established metastatic and autochthonous liver cancers in mouse models by preferentially expanding tumour-specific CD8(+) T cells and promoting their anti-tumour effects. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PKA and Epac cooperate to augment bradykinin-induced interleukin-8 release from human airway smooth muscle cells

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Halayko Andrew J

2009-09-01

Full Text Available Abstract Background Airway smooth muscle contributes to the pathogenesis of pulmonary diseases by secreting inflammatory mediators such as interleukin-8 (IL-8. IL-8 production is in part regulated via activation of Gq-and Gs-coupled receptors. Here we study the role of the cyclic AMP (cAMP effectors protein kinase A (PKA and exchange proteins directly activated by cAMP (Epac1 and Epac2 in the bradykinin-induced IL-8 release from a human airway smooth muscle cell line and the underlying molecular mechanisms of this response. Methods IL-8 release was assessed via ELISA under basal condition and after stimulation with bradykinin alone or in combination with fenoterol, the Epac activators 8-pCPT-2'-O-Me-cAMP and Sp-8-pCPT-2'-O-Me-cAMPS, the PKA activator 6-Bnz-cAMP and the cGMP analog 8-pCPT-2'-O-Me-cGMP. Where indicated, cells were pre-incubated with the pharmacological inhibitors Clostridium difficile toxin B-1470 (GTPases, U0126 (extracellular signal-regulated kinases ERK1/2 and Rp-8-CPT-cAMPS (PKA. The specificity of the cyclic nucleotide analogs was confirmed by measuring phosphorylation of the PKA substrate vasodilator-stimulated phosphoprotein. GTP-loading of Rap1 and Rap2 was evaluated via pull-down technique. Expression of Rap1, Rap2, Epac1 and Epac2 was assessed via western blot. Downregulation of Epac protein expression was achieved by siRNA. Unpaired or paired two-tailed Student's t test was used. Results The β2-agonist fenoterol augmented release of IL-8 by bradykinin. The PKA activator 6-Bnz-cAMP and the Epac activator 8-pCPT-2'-O-Me-cAMP significantly increased bradykinin-induced IL-8 release. The hydrolysis-resistant Epac activator Sp-8-pCPT-2'-O-Me-cAMPS mimicked the effects of 8-pCPT-2'-O-Me-cAMP, whereas the negative control 8-pCPT-2'-O-Me-cGMP did not. Fenoterol, forskolin and 6-Bnz-cAMP induced VASP phosphorylation, which was diminished by the PKA inhibitor Rp-8-CPT-cAMPS. 6-Bnz-cAMP and 8-pCPT-2'-O-Me-cAMP induced GTP

Enhanced interleukin-8 production in THP-1 human monocytic cells by lipopolysaccharide from oral microorganisms and granulocyte-macrophage colony-stimulating factor.

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Baqui, A A; Meiller, T F; Falkler, W A

1999-10-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been used to assist in bone marrow recovery during cancer chemotherapy. Interleukin-8 (IL-8) plays an important role in macrophage mediated inflammatory processes including exacerbation of periodontal diseases, one of the most common complications in GM-CSF receiving cancer patients. The effect of GM-CSF supplementation on IL-8 production was investigated in a human monocyte cell line THP-1, stimulated with lipopolysaccharide extracted from two oral microorganisms, Porphyromonas gingivalis and Fusobacterium nucleatum. Resting THP-1 cells were treated with lipopolysaccharide (1 microgram/ml) of P. gingivalis or F. nucleatum and/or GM-CSF (50 IU/ml) for varying time periods. The production of IL-8 in THP-1 cells was measured by a solid-phase enzyme-linked immunosorbent assay (ELISA). A very low level of the cytokine IL-8 was produced constitutive in THP-1 cells. Starting from 8 h of treatment and afterwards GM-CSF alone significantly increased IL-8 production in THP-1 cells. Lipopolysaccharide (1 microgram/ml) extracts from either F. nucleatum or P. gingivalis amplified IL-8 production 500-800 times in comparison to resting THP-1 cells. When lipopolysaccharide of F. nucleatum or P. gingivalis was supplemented with 50 IU/ml of GM-CSF, there was a statistically significant enhanced production of IL-8 by THP-1 cells after 1 day to 7 days of treatment as compared with lipopolysaccharide treatment alone. GM-CSF (50 IU/ml) also significantly increased IL-8 production from 2-7 days of treatment of THP-1 cells when supplemented with a positive control, phorbol-12-myristate-13 acetate (PMA), as compared to PMA treatment alone. These investigations using the in vitro THP-1 human monocyte cell model indicate that there may be an increase in the response on a cellular level to oral endotoxin following GM-CSF therapy as evidenced by enhanced production of the tissue-reactive inflammatory cytokine, IL-8.

Increased Interleukin-4 production by CD8 and gammadelta T cells in health-care workers is associated with the subsequent development of active tuberculosis.

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Ordway, Diane J; Costa, Leonor; Martins, Marta; Silveira, Henrique; Amaral, Leonard; Arroz, Maria J; Ventura, Fernando A; Dockrell, Hazel M

2004-08-15

We evaluated immune responses to Mycobacterium tuberculosis in 10 health-care workers (HCWs) and 10 non-HCWs and correlated their immune status with the development of active tuberculosis (TB). Twenty individuals were randomly recruited, tested, and monitored longitudinally for TB presentation. Peripheral blood mononuclear cells (PBMCs) from donors were stimulated with M. tuberculosis and tested for cell proliferation and the production of interferon (IFN)- gamma, interleukin (IL)-5, and IL-4, by use of enzyme-linked immunosorbent or flow-cytometric assays. HCWs had higher levels of cell proliferation (24,258 cpm) and IFN- gamma (6373 pg/mL) to M. tuberculosis than did non-HCWs (cell proliferation, 11,462 cpm; IFN- gamma, 3228 pg/mL). Six of 10 HCWs showed increased median percentages of CD8+IL-4+ (4.7%) and gammadelta +IL-4+ (2.3%) T cells and progressed to active TB. HCWs who remained healthy showed increased median percentages of CD8+IFN- gamma+ (25.0%) and gammadelta +IFN- gamma+ (8.0%) and lower percentages of CD8+IL-4+ (0.05%) and gammadelta +IL-4+ (0.03%) T cells.

Carrageenan activates monocytes via type-specific binding with interleukin-8: an implication for design of immuno-active biomaterials.

Science.gov (United States)

Chan, Weng-I; Zhang, Guangpan; Li, Xin; Leung, Chung-Hang; Ma, Dik-Lung; Dong, Lei; Wang, Chunming

2017-02-28

Polymers that can activate the immune system may become useful biomaterials tools, given that the mechanisms underlying their actions are well understood. Herein, we report a novel type of interaction between polymers and immune cells - in studying the influence of the three major types of carrageenan (CGN) polysaccharides on monocyte behaviour in vitro, we found only the λ-type induced monocyte adhesion and this action requires the presence of an adequate amount of serum. Further analyses indicated λ-CGN bound interleukin-8 (IL-8) in the serum and activated the cultured monocytes through an IL-8-dependent pathway. This is the first demonstration that a polymer, with a renowned immunostimulatory effect, activates the immune system via binding and harnessing the function of a specific cytokine in the microenvironment. This is a new mechanism underlying polymer-immunity interactions that may shed light on future design and application of biomaterials tools targeting the immune system for a wide variety of therapeutic applications.

Effect of the use of snuff on the levels of interleukin-1 β and interleukin-8 in the gingival crevicular fluid of periodontitis patients.

Science.gov (United States)

Pandey, Vijayendra; Salam, Sharib Abdus; Moda, Aman; Agarwal, Preeti; Nath, Sonia; Pulikkotil, Shaju Jacob

2015-01-01

Use of smokeless tobacco in the form of moist snuff placed in the oral cavity is popular in rural India. The aim of the present cross-sectional study was to determine the effect of snuff on periodontitis by assessing interleukin (IL)-1 β and IL-8 levels in gingival crevicular fluid. A total of 60 subjects were selected for this study. 40 subjects presented with periodontitis, which included 20 snuff users (SP) and 20 nonsnuff users (NS). 20 periodontally healthy patients formed the controls (healthy control: HC). The clinical parameters recorded were gingival index (GI), plaque index, calculus index, bleeding on probing (BOP), probing depth (PD), recession (RC), and clinical attachment level (CAL). The IL-1 β and IL-8 levels were assessed through enzyme-linked immunosorbent assay (Quantikine(®)). Analysis of variance (ANOVA), post-hoc Tukey's, Kruskal-Walli's ANOVA and Mann-Whitney test was used for comparison among groups and P > 0.05 was considered statistically significant. No significant difference was seen in levels of IL-1 β and IL-8 between SP and NS groups (P = 0.16, 0.97). However, both the periodontitis groups (SP and NS) had increased IL-β levels when compared to HC group (P = 0.01, 0.001). The snuff users showed significant increase in GI, BOP, RC, and CAL when compared with NS (P = 0.002, 0.001, 0.012, 0.002) whereas NS group had significant increase in PD (P = 0.003). Within the limitations of this study, use of snuff does not affect the host inflammatory response associated with periodontitis and leads to RC and increased CAL due to local irritant effect.

Parapoxvirus orf virus infection induces an increase in interleukin-8, tumour necrosis factor-α, and decorin in goat skin fibroblast cells

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Wang Lingling

2016-09-01

Full Text Available Introduction: Orf virus (ORFV is a prototype Parapoxvirus species in the Poxviridae family that causes serious zoonotic infectious disease. Goat skin fibroblast (GSF cells are the major host targets of ORFV. Interleukin 8 (IL-8 and tumour necrosis factor (TNF-α are known to play a vital role in immune response during viral infections. However, the manner of variation over time of their level of expression in GSF cells remains unclear.

ROS and NF-κB are involved in upregulation of IL-8 in A549 cells exposed to multi-walled carbon nanotubes

International Nuclear Information System (INIS)

Ye Shefang; Wu Yihui; Hou Zhenqing; Zhang Qiqing

2009-01-01

Carbon nanotubes (CNTs) have potential applications in biosensors, tissue engineering, and biomedical devices because of their unique physico-chemical, electronic and mechanical properties. However, there is limited literature data available concerning the biological properties and toxicity of CNTs. This study aimed to assess the toxicity exhibited by multi-walled CNTs (MWCNTs) and to elucidate possible molecular mechanisms underlying the biological effects of MWCNTs in A549 cells. Exposing A549 cells to MWCNTs led to cell death, changes in cell size and complexity, reactive oxygen species (ROS) production, interleukin-8 (IL-8) gene expression and nuclear factor (NF)-κB activation. Treatment of A549 cells with antioxidants prior to adding MWCNTs decreased ROS production and abrogated expression of IL-8 mRNA. Pretreatment of A549 cells with NF-κB inhibitors suppressed MWCNTs-induced IL-8 mRNA expression. These results indicate that MWCNTs are able to induce expression of IL-8 in A549 cells, at least in part, mediated by oxidative stress and NF-κB activation.

Identification and expression analysis of two pro-inflammatory cytokines, TNF-α and IL-8, in cobia (Rachycentron canadum L.) in response to Streptococcus dysgalactiae infection.

Science.gov (United States)

Nguyen, Thuy Thi Thu; Nguyen, Hai Trong; Wang, Pei-Chyi; Chen, Shih-Chu

2017-08-01

Tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8/CXCL8) play pivotal roles in mediating inflammatory responses to invading pathogens. In this study, we identified and analyzed expressions of cobia TNF-α and IL-8 during Streptococcus dysgalactiae infection. The cloned cDNA transcript of cobia TNF-α comprised of 1281 base pairs (bp), with a 774 bp open reading frame (ORF) encoding 257 amino acids. The deduced amino acid sequence of cobia TNF-α showed a close relationship (84% similarity) with TNF-α of yellowtail amberjack. The cloned IL-8 cDNA sequence was 828 bp long, including a 300-bp ORF encoding 99 amino acids. The deduced amino acid sequence of cobia IL-8 shared 90% identity with IL-8 of striped trumpeter. Cobia challenged with a virulent S. dysgalactiae strain displayed an early significant up-regulation of TNF-α and IL-8 in head kidney, liver, and spleen. Notably, IL-8 expression level increased dramatically in the liver at the severe stage of infection (72 h). In conclusion, a better understanding of TNF-α and IL-8 allows more detailed investigation of immune responses in cobia and furthers study on controlling the infectious disease caused by S. dysgalactiae. Copyright © 2017 Elsevier Ltd. All rights reserved.

Study on the changes of serum IL-2, IL-6, IL-8 and TNF levels in patients with diabetic nephrosis

International Nuclear Information System (INIS)

Qin Wenjing

2005-01-01

Objective: To investigate the changes of serum IL-2, IL-6, IL-8 and TNF levels in patients with diabetic nephrosis. Methods: Serum IL-2, IL-6, IL-8 and TNF levels were measured with RIA in 38 patients with diabetic nephrosis and 36 controls. Results: Serum levels of IL-6, IL-8 and TNF were significantly higher in patients with diabetic nephrosis than those in controls (P<0.01), but serum IL-2 levels were significantly lower in the patients (P<0.01). Conclusion: These cytokines participated in the pathogenesis of diabetic nephrosis. Monitoring the changes of their serum levels was helpful for the management of the disease. (authors)

Cerebrospinal fluid and serum levels of interleukin-8 in patients with multiple sclerosis and its correlation with Q-albumin.

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Matejčíková, Z; Mareš, J; Sládková, V; Svrčinová, T; Vysloužilová, J; Zapletalová, J; Kaňovský, P

2017-05-01

Multiple sclerosis (MS) is an inflammatory-demyelinating disease of the central nervous system (CNS). Autoimmune inflammation is common in the early stages of MS and is followed by neurodegenerative processes. The result of these changes is axon and myelin breakdown. The paraclinical examination methods are an important part of the diagnostic process. Magnetic resonance imaging of the brain and the cervical spinal cord and an examination of cerebrospinal fluid (CSF) are common paraclinical examinations. An increasing number of studies deal with CSF and serum levels of biomarkers and their role in MS. We hypothesized that the level of interleukin-8 (IL-8) could be different in MS patients than in controls. These differences may be related to damage of the blood-brain barrier (BBB). BBB damage is quantified by the quotient of albumin (Q-alb). CSF and serum levels of IL-8 were assessed in 102 patients with newly diagnosed MS meeting McDonald's revised diagnostic criteria and in 102 subjects as a control group. We then correlated these results with Q-alb. Levels of IL-8 in CSF were significantly higher in MS patients than in controls (Mann-Whitney U test, p<0.0001). Serum levels of IL-8 were significantly lower in MS patients than in controls (Mann-Whitney U test, p=0.018). Spearman's correlation analysis proved a significant correlation between levels of IL-8 and Q-alb. As the etiology of MS is only partially known, research dealing with biomarkers in MS should continue. Better knowledge of etiology can provide a new perspective, especially for treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential expression of interleukin-8 by polymorphonuclear leukocytes of two closely related species, Ovis canadensis and Ovis aries, in response to Mannheimia haemolytica infection.

Science.gov (United States)

Herndon, Caroline N; Foreyt, William J; Srikumaran, Subramaniam

2010-08-01

The pneumonic lesions and mortality caused by Mannheimia haemolytica in bighorn sheep (BHS; Ovis canadensis) are more severe than those in the related species, domestic sheep (DS; Ovis aries), under both natural and experimental conditions. Leukotoxin (Lkt) and lipopolysaccharide (LPS) are the most important virulence factors of this organism. One hallmark of pathogenesis of pneumonia is the influx of polymorphonuclear leukocytes (PMNs) into the lungs. Lkt-induced cytolysis of PMNs results in the release of cytotoxic compounds capable of damaging lung tissue. Interleukin-8 (IL-8) is a potent PMN chemoattractant. The objective of the present study was to determine if there is differential expression of IL-8 by the macrophages and PMNs of BHS and DS in response to M. haemolytica. Macrophages and PMNs of BHS and DS were stimulated with heat-killed M. haemolytica or LPS. IL-8 expression by the cells was measured by enzyme-linked immunosorbent assays and real-time reverse transcription-PCR (RT-PCR). The PMNs of BHS expressed severalfold higher levels of IL-8 than those of DS upon stimulation. Lesional lung tissue of M. haemolytica-infected BHS contained significantly higher levels of IL-8 than nonlesional tissue. The bronchoalveolar lavage (BAL) fluid of infected BHS also contained higher levels of IL-8 than that of infected DS. Depletion of IL-8 reduced migration of PMNs toward BAL fluid by approximately 50%, indicating that IL-8 is integral to PMN recruitment to the lung during M. haemolytica infection. Excessive production of IL-8, enhanced recruitment of PMNs, and PMN lysis by Lkt are likely responsible for the severity of the lung lesions in M. haemolytica-infected BHS.

Tissue factor-factor VIIa-specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration

DEFF Research Database (Denmark)

Hjortoe, Gertrud M; Petersen, Lars C; Albrektsen, Tatjana

2004-01-01

Tissue factor (TF), the cellular receptor for factor VIIa (FVIIa), besides initiating blood coagulation, is believed to play an important role in tissue repair, inflammation, angiogenesis, and tumor metastasis. Like TF, the chemokine interleukin-8 (IL-8) is shown to play a critical role...... in these processes. To elucidate the potential mechanisms by which TF contributes to tumor invasion and metastasis, we investigated the effect of FVIIa on IL-8 expression and cell migration in a breast carcinoma cell line, MDA-MB-231, a cell line that constitutively expresses abundant TF. Expression of IL-8 m......RNA in MDA-MB-231 cells was markedly up-regulated by plasma concentrations of FVII or an equivalent concentration of FVIIa (10 nM). Neither thrombin nor other proteases involved in hemostasis were effective in stimulating IL-8 in these cells. Increased transcriptional activation of the IL-8 gene...

Association of Genetic Polymorphism in the Interleukin-8 Gene with Risk of Oral Cancer and Its Correlation with Pain.

Science.gov (United States)

Singh, Prithvi Kumar; Chandra, Girish; Bogra, Jaishri; Gupta, Rajni; Kumar, Vijay; Hussain, Syed Rizwan; Jain, Amita; Mahdi, Abbas Ali; Ahmad, Mohammad Kaleem

2016-02-01

Oral cancer is a multifactorial disease process and involves complex interactions between gene to gene and gene to environmental factors. Interleukin 8 (IL-8), a pro-inflammatory cytokine, having angiogenic activity with elevated expression in tumor cells, is reported to play an essential role in oral cancer development. This study was conducted with the aim to investigate the role of IL-8 (-A251T) gene polymorphism in susceptibility, progression, and self-reporting pain in oral cancer. The single nucleotide polymorphisms of the IL-8 (-A251T) gene were screened in 300 patients with oral cancer and 300 healthy controls, by polymerase chain reaction-restriction fragment length polymorphism. Genotype and allele frequencies were evaluated by chi-square test and odds ratio (OR) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. The results of the study demonstrated that IL-8 (-A251T) gene polymorphism was significantly associated with susceptibility of oral cancer, whereas its correlation with clinico-pathological status or pain due to oral cancer could not be established. The AT heterozygous (OR 5.31; CI 3.38-8.34; p 0.0001) and AA homozygous (OR 2.89; CI 1.76-4.75; p 0.0001) had a greater risk for oral cancer compared to TT homozygous. Furthermore, significantly increased values of A allele frequencies compared to T allele were observed in all patients (OR 1.56; CI 1.24-1.96; p 0.0002). Tobacco chewing and smoking were also found to influence the development of oral cancer and increased the incidence of pain in oral cancer patients. The findings of this study suggest that the IL-8 (-A251T) gene polymorphism may be associated with increased risk of oral cancer.

Reduction of Monocyte Chemoattractant Protein-1 and Interleukin-8 Levels by Ticlopidine in TNF-α Stimulated Human Umbilical Vein Endothelial Cells

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Chaur-Jong Hu

2009-01-01

Full Text Available Atherosclerosis and its associated complications represent major causes of morbidity and mortality in the industrialized or Western countries. Monocyte chemoattractant protein-1 (MCP-1 is critical for the initiating and developing of atherosclerotic lesions. Interleukin-8 (IL-8, a CXC chemokine, stimulates neutrophil chemotaxis. Ticlopidine is one of the antiplatelet drugs used to prevent thrombus formation relevant to the pathophysiology of atherothrombosis. In this study, we found that ticlopidine dose-dependently decreased the mRNA and protein levels of TNF-α-stimulated MCP-1, IL-8, and vascular cell adhesion molecule-1 (VCAM-1 in human umbilical vein endothelial cells (HUVECs. Ticlopidine declined U937 cells adhesion and chemotaxis as compared to TNF-α stimulated alone. Furthermore, the inhibitory effects were neither due to decreased HUVEC viability, nor through NF-kB inhibition. These results suggest that ticlopidine decreased TNF-α induced MCP-1, IL-8, and VCAM-1 levels in HUVECs, and monocyte adhesion. Therefore, the data provide additional therapeutic machinery of ticlopidine in treatment and prevention of atherosclerosis.

Cigarette smoke regulates the expression of TLR4 and IL-8 production by human macrophages

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Rahman Irfan

2009-05-01

Full Text Available Abstract Background Toll-like receptors (TLRs are present on monocytes and alveolar macrophages that form the first line of defense against inhaled particles. The importance of those cells in the pathophysiology of chronic obstructive pulmonary disease (COPD has well been documented. Cigarette smoke contains high concentration of oxidants which can stimulate immune cells to produce reactive oxygen species, cytokines and chemokines. Methods In this study, we evaluated the effects of cigarette smoke medium (CSM on TLR4 expression and interleukin (IL-8 production by human macrophages investigating the involvement of ROS. Results and Discussion TLR4 surface expression was downregulated on short term exposure (1 h of CSM. The downregulation could be explained by internalization of the TLR4 and the upregulation by an increase in TLR4 mRNA. IL-8 mRNA and protein were also increased by CSM. CSM stimulation increased intracellular ROS-production and decreased glutathione (GSH levels. The modulation of TLR4 mRNA and surface receptors expression, IRAK activation, IκB-α degradation, IL-8 mRNA and protein, GSH depletion and ROS production were all prevented by antioxidants such as N-acetyl-L-cysteine (NAC. Conclusion TLR4 may be involved in the pathogenesis of lung emphysema and oxidative stress and seems to be a crucial contributor in lung inflammation.

Expression profiles of the immune genes CD4, CD8β, IFNγ, IL-4, IL-6 and IL-10 in mitogen-stimulated koala lymphocytes (Phascolarctos cinereus by qRT-PCR

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Iona E. Maher

2014-03-01

Full Text Available Investigation of the immune response of the koala (Phascolarctos cinereus is needed urgently, but has been limited by scarcity of species-specific reagents and methods for this unique and divergent marsupial. Infectious disease is an important threat to wild populations of koalas; the most widespread and important of these is Chlamydial disease, caused by Chlamydia pecorum and Chlamydia pneumoniae. In addition, koala retrovirus (KoRV, which is of 100% prevalence in northern Australia, has been proposed as an important agent of immune suppression that could explain the koala’s susceptibility to disease. The correct balance of T regulatory, T helper 1 (Th1 and Th2 lymphocyte responses are important to an individual’s susceptibility or resistance to chlamydial infection. The ability to study chlamydial or KoRV pathogenesis, effects of environmental stressors on immunity, and the response of koalas to vaccines under development, by examining the koala’s adaptive response to natural infection or in-vitro stimulation, has been limited to date by a paucity of species- specific reagents. In this study we have used cytokine sequences from four marsupial genomes to identify mRNA sequences for key T regulatory, Th1 and Th2 cytokines interleukin 4 (IL-4, interleukin 6 (IL-6, interleukin 10 (IL-10 and interferon gamma (IFNγ along with CD4 and CD8β. The koala sequences used for primer design showed >58% homology with grey short-tailed opossum, >71% with tammar wallaby and 78% with Tasmanian devil amino acid sequences. We report the development of real-time RT-PCR assays to measure the expression of these genes in unstimulated cells and after three common mitogen stimulation protocols (phorbol myristate acetate/ionomycin, phorbol myristate acetate/phytohemagglutinin and concanavalin A. Phorbol myristate acetate/ionomycin was found to be the most effective mitogen to up-regulate the production of IL-4, IL-10 and IFNγ. IL-6 production was not

Expression profiles of the immune genes CD4, CD8β, IFNγ, IL-4, IL-6 and IL-10 in mitogen-stimulated koala lymphocytes (Phascolarctos cinereus) by qRT-PCR.

Science.gov (United States)

Maher, Iona E; Griffith, Joanna E; Lau, Quintin; Reeves, Thomas; Higgins, Damien P

2014-01-01

Investigation of the immune response of the koala (Phascolarctos cinereus) is needed urgently, but has been limited by scarcity of species-specific reagents and methods for this unique and divergent marsupial. Infectious disease is an important threat to wild populations of koalas; the most widespread and important of these is Chlamydial disease, caused by Chlamydia pecorum and Chlamydia pneumoniae. In addition, koala retrovirus (KoRV), which is of 100% prevalence in northern Australia, has been proposed as an important agent of immune suppression that could explain the koala's susceptibility to disease. The correct balance of T regulatory, T helper 1 (Th1) and Th2 lymphocyte responses are important to an individual's susceptibility or resistance to chlamydial infection. The ability to study chlamydial or KoRV pathogenesis, effects of environmental stressors on immunity, and the response of koalas to vaccines under development, by examining the koala's adaptive response to natural infection or in-vitro stimulation, has been limited to date by a paucity of species- specific reagents. In this study we have used cytokine sequences from four marsupial genomes to identify mRNA sequences for key T regulatory, Th1 and Th2 cytokines interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10) and interferon gamma (IFNγ) along with CD4 and CD8β. The koala sequences used for primer design showed >58% homology with grey short-tailed opossum, >71% with tammar wallaby and 78% with Tasmanian devil amino acid sequences. We report the development of real-time RT-PCR assays to measure the expression of these genes in unstimulated cells and after three common mitogen stimulation protocols (phorbol myristate acetate/ionomycin, phorbol myristate acetate/phytohemagglutinin and concanavalin A). Phorbol myristate acetate/ionomycin was found to be the most effective mitogen to up-regulate the production of IL-4, IL-10 and IFNγ. IL-6 production was not consistently up-regulated by

Depletion of intrinsic expression of Interleukin-8 in prostate cancer cells causes cell cycle arrest, spontaneous apoptosis and increases the efficacy of chemotherapeutic drugs

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Lokeshwar Bal L

2009-07-01

Full Text Available Abstract Background The progression of all cancers is characterized by increased-cell proliferation and decreased-apoptosis. The androgen-independent prostate cancer (AIPC is the terminal stage of the disease. Many chemokines and cytokines are suspects to cause this increased tumor cell survival that ultimately leads to resistance to therapy and demise of the host. The AIPC cells, but not androgen-responsive cells, constitutively express abundant amount of the pro-inflammatory chemokine, Interleukin-8 (IL-8. The mechanism of IL-8 mediated survival and therapeutic resistance in AIPC cells is unclear at present. The purpose of this report is to show the pervasive role of IL-8 in malignant progression of androgen-independent prostate cancer (AIPC and to provide a potential new therapeutic avenue, using RNA interference. Results The functional consequence of IL-8 depletion in AIPC cells was investigated by RNA interference in two IL-8 secreting AIPC cell lines, PC-3 and DU145. The non-IL-8 secreting LNCaP and LAPC-4 cells served as controls. Cells were transfected with RISC-free siRNA (control or validated-pool of IL-8 siRNA. Transfection with 50 nM IL-8 siRNA caused >95% depletion of IL-8 mRNA and >92% decrease in IL-8 protein. This reduction in IL-8 led to cell cycle arrest at G1/S boundary and decreases in cell cycle-regulated proteins: Cyclin D1 and Cyclin B1 (both decreased >50% and inhibition of ERK1/2 activity by >50%. Further, the spontaneous apoptosis was increased by >43% in IL-8 depleted cells, evidenced by increases in caspase-9 activation and cleaved-PARP. IL-8 depletion caused significant decreases in anti-apoptotic proteins, BCL-2, BCL-xL due to decrease in both mRNA and post-translational stability, and increased levels of pro-apoptotic BAX and BAD proteins. More significantly, depletion of intracellular IL-8 increased the cytotoxic activity of multiple chemotherapeutic drugs. Specifically, the cytotoxicity of Docetaxel

Clinical significance of determination of some serum cytokines (IL-8, IL-10, IL-18, M-CSF) levels in patients with periodontitis

International Nuclear Information System (INIS)

Wei Dong; Zhang Xiaolei; Yang Chunxiu; Chen Guanghua

2008-01-01

Objective: To explore the significance of changes of serum IL-8, IL-10, IL-18 and M-CSF levels in patients with periodontitis. Methods: Serum levels of IL-8, IL-10, M-CSF (with RIA) and IL-18 (with ELISA) were measured in 55 patients with periodontitis both before and after treatment as well as in 35 controls. Results: Before treatment, serum levels of IL-8, IL-10, IL-18 and M-CSF were significantly higher in the patients than those in the controls (P<0.01). After one month of treatment, the serum IL-8, IL-10, IL-18 and M-CSF levels decreased somewhat, but were still significantly higher than those in controls (P<0.05). Conclusion: There was disturbance of immunomodulation in patients with periodontitis as expressed by the changes of several cytokines levels in the eourse of the diseases. (authors)

Effect of the use of snuff on the levels of interleukin-1 β and interleukin-8 in the gingival crevicular fluid of periodontitis patients

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Vijayendra Pandey

2015-01-01

Full Text Available Background: Use of smokeless tobacco in the form of moist snuff placed in the oral cavity is popular in rural India. The aim of the present cross-sectional study was to determine the effect of snuff on periodontitis by assessing interleukin (IL-1 β and IL-8 levels in gingival crevicular fluid. Materials and Methods: A total of 60 subjects were selected for this study. 40 subjects presented with periodontitis, which included 20 snuff users (SP and 20 nonsnuff users (NS. 20 periodontally healthy patients formed the controls (healthy control: HC. The clinical parameters recorded were gingival index (GI, plaque index, calculus index, bleeding on probing (BOP, probing depth (PD, recession (RC, and clinical attachment level (CAL. The IL-1 β and IL-8 levels were assessed through enzyme-linked immunosorbent assay (Quantikine ®. Analysis of variance (ANOVA, post-hoc Tukey′s, Kruskal-Walli′s ANOVA and Mann-Whitney test was used for comparison among groups and P > 0.05 was considered statistically significant. Results: No significant difference was seen in levels of IL-1 β and IL-8 between SP and NS groups (P = 0.16, 0.97. However, both the periodontitis groups (SP and NS had increased IL-β levels when compared to HC group (P = 0.01, 0.001. The snuff users showed significant increase in GI, BOP, RC, and CAL when compared with NS (P = 0.002, 0.001, 0.012, 0.002 whereas NS group had significant increase in PD (P = 0.003. Conclusion: Within the limitations of this study, use of snuff does not affect the host inflammatory response associated with periodontitis and leads to RC and increased CAL due to local irritant effect.

Nebulized hypertonic saline decreases IL-8 in sputum of patients with cystic fibrosis.

LENUS (Irish Health Repository)

Reeves, Emer P

2012-02-01

RATIONALE: Inflammation within the cystic fibrosis (CF) lung is mediated by inflammatory chemokines, such as IL-8. IL-8 is protected from proteolytic degradation in the airways by binding to glycosaminoglycans, while remaining active. Evidence that increased hypertonicity of airway secretions induced by hypertonic saline treatment alters levels of IL-8 is lacking. OBJECTIVES: To investigate the antiinflammatory effect of hypertonic saline (HTS) treatment within the CF lung by focusing on IL-8. METHODS: Degradation of IL-8 in CF lung secretions after treatment with glycosaminoglycan lyases and HTS was analyzed by Western blot analysis and ELISA. The ex vivo chemotactic activity of purified neutrophils in response to CF airway secretions was evaluated post nebulization of HTS (7% saline). MEASUREMENTS AND MAIN RESULTS: In vivo CF bronchoalveolar lavage fluid (BALF) IL-8 levels were significantly higher than the control group (P < 0.05). Digesting glycosaminoglycans in CF BALF displaced IL-8 from glycosaminoglycan matrices, rendering the chemokine susceptible to proteolytic cleavage. High sodium concentrations also liberate IL-8 in CF BALF in vitro, and in vivo in CF sputum from patients receiving aerosolized HTS, resulting in degradation of IL-8 and decreased neutrophil chemotactic efficiency. CONCLUSIONS: Glycosaminoglycans possess the ability to influence the chemokine profile of the CF lung by binding and stabilizing IL-8, which promotes neutrophil chemotaxis and activation. Nebulized hypertonic saline treatment disrupts the interaction between glycosaminoglycans and IL-8, rendering IL-8 susceptible to proteolytic degradation with subsequent decrease in neutrophil chemotaxis, thereby facilitating resolution of inflammation.

Sphingosine 1-phosphate induces neutrophil chemoattractant IL-8: repression by steroids.

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Md Mostafizur Rahman

Full Text Available The bioactive sphingolipid sphingosine 1-phosphate (S1P is found in increased amounts in the airways of asthmatics. S1P can regulate airway smooth muscle functions associated with asthmatic inflammation and remodeling, including cytokine secretion. To date however, whether S1P induces secretion of an important chemokine responsible for neutrophilia in airway inflammation--IL-8--was unexplored. The aim of this study was to investigate whether S1P induces IL-8 gene expression and secretion to enhance neutrophil chemotaxis in vitro, as well as examine the molecular mechanisms responsible for repression by the corticosteroid dexamethasone. We show that S1P upregulates IL-8 secretion from ASM cells and enhance neutrophil chemotaxis in vitro. The corticosteroid dexamethasone significantly represses IL-8 mRNA expression and protein secretion in a concentration- and time-dependent manner. Additionally, we reveal that S1P-induced IL-8 secretion is p38 MAPK and ERK-dependent and that these key phosphoproteins act on the downstream effector mitogen- and stress-activated kinase 1 (MSK1 to control secretion of the neutrophil chemoattractant cytokine IL-8. The functional relevance of this in vitro data was demonstrated by neutrophil chemotaxis assays where S1P-induced effects can be significantly attenuated by pretreatment with dexamethasone, pharmacological inhibition of p38 MAPK- or ERK-mediated pathways, or by knocking down MSK-1 with siRNA. Taken together, our study reveals the molecular pathways responsible for IL-8 secretion from ASM cells in response to S1P and indicates ways in which the impact on IL-8-driven neutrophilia may be lessened.

Both direct and indirect effects account for the pro-inflammatory activity of enteropathogenic mycotoxins on the human intestinal epithelium: Stimulation of interleukin-8 secretion, potentiation of interleukin-1β effect and increase in the transepithelial passage of commensal bacteria

International Nuclear Information System (INIS)

Maresca, Marc; Yahi, Nouara; Younes-Sakr, Lama; Boyron, Marilyn; Caporiccio, Bertrand; Fantini, Jacques

2008-01-01

Mycotoxins are fungal secondary metabolites responsible of food-mediated intoxication in animals and humans. Deoxynivalenol, ochratoxin A and patulin are the best known enteropathogenic mycotoxins able to alter intestinal functions resulting in malnutrition, diarrhea, vomiting and intestinal inflammation in vivo. Although their effects on intestinal barrier and transport activities have been extensively characterized, the mechanisms responsible for their pro-inflammatory effect are still poorly understood. Here we investigated if mycotoxin-induced intestinal inflammation results from a direct and/or indirect pro-inflammatory activity of these mycotoxins on human intestinal epithelial cells, using differentiated Caco-2 cells as model and interleukin 8 (IL-8) as an indicator of intestinal inflammation. Deoxynivalenol was the only mycotoxin able to directly increase IL-8 secretion (10- to 15-fold increase). We also investigated if these mycotoxins could indirectly stimulate IL-8 secretion through: (i) a modulation of the action of pro-inflammatory molecules such as the interleukin-1beta (IL-1β), and/or (ii) an increase in the transepithelial passage of non-invasive commensal Escherichia coli. We found that deoxynivalenol, ochratoxin A and patulin all potentiated the effect of IL-1β on IL-8 secretion (ranging from 35% to 138% increase) and increased the transepithelial passage of commensal bacteria (ranging from 12- to 1544-fold increase). In addition to potentially exacerbate established intestinal inflammation, these mycotoxins may thus participate in the induction of sepsis and intestinal inflammation in vivo. Taken together, our results suggest that the pro-inflammatory activity of enteropathogenic mycotoxins is mediated by both direct and indirect effects

Interleukin-2 and Interleukin-8 Gene Polymorphisms and Acquired Aplastic Anemia Risk in a Chinese Population.

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Zhang, Xuejie; Lin, Shengyun; Yang, Yan; Rong, Liucheng; He, Guangsheng; He, Hailong; Xue, Yao; Fang, Yongjun; Wang, Yaping

2017-01-01

Cytokines IL-2 and IL-8 both participate in immune regulation. However, the relationship between polymorphisms in these two cytokines and the risk of acquired aplastic anemia (acquired AA) has not been explored. We selected five SNPs including rs11575812, rs2069772 and rs2069762 of IL-2, rs2227306 and rs2227543 of IL-8. SNaPshot genotyping was used to test the genotypes of IL-2 and IL-8 polymorphisms in a population of 101 acquired AA patients and 165 healthy controls. The rs2069762 G allele appeared to be a protective mutation, but no significant differences were found in other four SNPs. We also found that rs2069762 had an impact on the transcriptional regulation. It could be assumed that the rs2069762 polymorphism might reduce the risk of acquired aplastic anemia, while the remaining four SNPs might not contribute to susceptibility to acquired AA in a Chinese population. © 2017 The Author(s)Published by S. Karger AG, Basel.

Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family.

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Cayrol, Corinne; Girard, Jean-Philippe

2018-01-01

Interleukin-33 (IL-33) is a tissue-derived nuclear cytokine from the IL-1 family abundantly expressed in endothelial cells, epithelial cells and fibroblast-like cells, both during homeostasis and inflammation. It functions as an alarm signal (alarmin) released upon cell injury or tissue damage to alert immune cells expressing the ST2 receptor (IL-1RL1). The major targets of IL-33 in vivo are tissue-resident immune cells such as mast cells, group 2 innate lymphoid cells (ILC2s) and regulatory T cells (Tregs). Other cellular targets include T helper 2 (Th2) cells, eosinophils, basophils, dendritic cells, Th1 cells, CD8 + T cells, NK cells, iNKT cells, B cells, neutrophils and macrophages. IL-33 is thus emerging as a crucial immune modulator with pleiotropic activities in type-2, type-1 and regulatory immune responses, and important roles in allergic, fibrotic, infectious, and chronic inflammatory diseases. The critical function of IL-33/ST2 signaling in allergic inflammation is illustrated by the fact that IL33 and IL1RL1 are among the most highly replicated susceptibility loci for asthma. In this review, we highlight 15 years of discoveries on IL-33 protein, including its molecular characteristics, nuclear localization, bioactive forms, cellular sources, mechanisms of release and regulation by proteases. Importantly, we emphasize data that have been validated using IL-33-deficient cells. © 2017 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.

Clinical significance of determination of changes of serum IL-6, IL-8, IL-10 and IL-18 levels after treatment in patients with chronic renal diseases

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Liu Congjiang; Li Fen; Zhang Lei; Liu Jianhua

2008-01-01

Objective: To explore the changes of serum IL-6, IL-8, IL-10 and IL-18 levels after treatment in patients with chronic renal diseases. Methods: Serum IL-6, IL-8, IL-10 levels were determined with RIA and IL-18 levels with ELISA in 32 patients with chronic renal diseases both before and after treatment as well as in 35 controls. Results: Before treatment the serum IL -6, IL-8, IL-10 and IL-18 levels were significantly higher in the patients than those in controls (P<0.01). After 6 months of treatment, the levels though dropped markedly remained significantly higher (P<0.05). Conclusion: Levels of serum IL-6, IL- 8, IL-10 and IL-18 increased significantly in patients with chronic renal diseases, especially in those advanced cases. (authors)

Murine analogues of etanercept and of F8-IL10 inhibit the progression of collagen-induced arthritis in the mouse.

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Doll, Fabia; Schwager, Kathrin; Hemmerle, Teresa; Neri, Dario

2013-09-27

Etanercept is a fusion protein consisting of the soluble portion of the p75-tumor necrosis factor receptor (TNFR) and the Fc fragment of human IgG1, which is often used for the treatment of patients with rheumatoid arthritis. F8-IL10 is a human immunocytokine based on the F8 antibody and interleukin-10, which is currently being investigated in rheumatoid arthritis with promising clinical results. We have aimed at expressing murine versions of these two fusion proteins, in order to assess their pharmaceutical performance in the collagen-induced model of rheumatoid arthritis in the mouse. Two fusion proteins (termed muTNFR-Fc and F8-muIL10) were cloned, expressed in chinese hamster ovary (CHO) cells, purified and characterized. Biological activity of muTNFR-Fc was assessed by its ability to inhibit TNF-induced killing of mouse fibroblasts, while F8-muIL10 was characterized in terms of muIL10 activity, of binding affinity to the cognate antigen of F8, the alternatively-spliced EDA domain of fibronectin, by quantitative biodistribution analysis and in vivo imaging. The therapeutic activity of both fusion proteins was investigated in a collagen-induced mouse model of arthritis. Mouse plasma was analyzed for anti-drug antibody formation and cytokine levels were determined by bead-based multiplex technology. The association of F8-IL10 proteins with blood cells was studied in a centrifugation assay with radiolabeled protein. Both fusion proteins exhibited excellent purity and full biological activity in vitro. In addition, F8-muIL10 was able to localize on newly-formed blood vessels in vivo. When used in a murine model of arthritis, the two proteins inhibited arthritis progression. The activity of muTNFR-Fc was tested alone and in combination with F8-huIL10. The chimeric version of F8-IL10 was not better then the fully human fusion protein and showed similar generation of mouse anti-fusion protein antibodies. Incubation studies of F8-muIL10 and F8-huIL10 with blood

Clinical significance of changes of levels of serum IL-2, IL-8, IL-10 and gastrin in patients with chronic eczema

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Huang Haifeng; Bi Mingye; Shi Hejian

2009-01-01

Objective: To study the significance of changes of serum IL-2, IL-8, IL-10 and Gastrin levels in patients with chronic eczema. Methods: Serum levels of IL-2, IL-8, IL-10 and Gastrin were determined with RIA in 30 patients with chronic eczema and 30 controls. Results: The levels of serum IL-2 were significantly lower in the eczema patients than those in controls (P 0.05). Both serum IL-10 and Gastrin levels were significantly higher in the patients than those in controls (P<0.01). Conclusion: Determination of serum IL-2, IL-8, IL-10 and Gastrin levels in patients with chronic eczema would be of help in monitoring the disease process and outcome prediction. (authors)

Fluoride-induced IL-8 release in human epithelial lung cells: Relationship to EGF-receptor-, SRC- and MAP-kinase activation

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Refsnes, Magne; Skuland, Tonje; Schwarze, Per E.; Ovrevik, Johan; Lag, Marit

2008-01-01

Exposure of human epithelial lung cells to fluorides is known to induce a marked increase in the release of interleukin (IL)-8, a chemokine involved in neutrophil recruitment. In the present study, the involvement of mitogen-activating protein kinases (MAPKs), the role of upstream activation of Src family kinases (SFKs), epidermal growth factor receptor (EGFR) activation and the interrelationships between these pathways in fluoride-induced IL-8 were examined in a human epithelial lung cell line (A549). Sodium fluoride strongly activated MAPK, in particular JNK1/2 and p38. The ERK1/2-inhibitor PD98059, the p38-inhibitor SB202190 and the JNK1/2-inhibitor SP600125 partially inhibited the fluoride-induced IL-8 response. Combinations of these inhibitors reduced the responses nearly to basal levels. Treatment with siRNA against JNK2 also reduced the IL-8 response to fluoride. Furthermore, fluoride activated SFKs, which was abolished by the SFK-inhibitor PP2. PP2 substantially inhibited the increased levels of IL-8, and partially reduced the fluoride-induced activation of ERK1/2, p38 and JNK1/2. Fluoride exposure also led to a phosphorylation of the EGFR, that was partially inhibited by PP2. AG1478, an EGFR-inhibitor, partially reduced the fluoride-induced IL-8 response and the phosphorylation of JNK1/2 and ERK1/2, but less the phosphorylation of p38. The effects of AG1478 were less than that of PP2. In conclusion, our findings suggest that the fluoride-induced IL-8 release involves the combined activation of ERK1/2, JNK1/2 and p38, and that the phosphorylation of these kinases, and in particular JNK1/2 and ERK1/2, partly, is mediated via a SFK-dependent EGFR-linked pathway. SFK-dependent, but EGFR-independent mechanisms seem important, and especially for phosphorylation of p38

Study on the changes of serum TNF-α, IL-1β, IL-6 and IL-8 levels in patients with coronary cardiac heart diseases

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Lu Xiaozhuo; Yu Xian

2003-01-01

Objective: To study the role TNF-α, IL-1β, IL-6 and IL-8 played in the pathogenesis of coronary cardiac heart diseases. Methods: Serum levels of TNF-α, IL-1β, IL-6 and IL-8 levels were determined by chemiluminescence immunoassay in 32 patients with stable angina, 39 patients with acute myocardial infarction and 36 controls. Results: Serum TNF-α, IL-1β, IL-6 and IL-8 levels in all patients were higher than those in controls. Remarkably increased level were seen in acute myocardial infarction group. Difference between control and patient groups were: stable angina group TNF-α, p<0.05, IL-6, p<0.01 and IL-8, p<0.05; acute myocardial infarction group TNF-α, p<0.01, IL-1β, p<0.05, IL-6, p<0.001 and IL-8, p<0.001. Conclusion: There is close relationship between serum TNF-α, IL-1β, IL-6, IL-8 levels and development of coronary cardiac heart disease. They play an important role in the pathogenesis through mutual induction and synergistic actions

EVALUATION OF THE ROLE OF INTERLEUKIN-8 (IL -8), SOLUBLE INTERCELLULAR ADHESION MOLECULE-1(SICAM-1) AND EOSINOPHIL CATIONIC PROTEIN (ECP) IN PATHOGENESIS OF BRONCHIAL ASTHMA

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EL-NASHAR, N.A.; MOSTAFA, A.M.E.; AHMED, S.M.; ABDEL-LATIF, A.

2008-01-01

Bronchial asthma remains a leading cause of chronic illness in children. Current theories of the pathogenesis of asthma suggest that airway inflammation is an important determinant of bronchial hyperactivity .The interaction of several inflammatory cells, soluble mediators and adhesion molecules may be important determinants of asthma. Since a better understanding of the underlying mechanisms leading to asthma pathology may yield more specific immunological strategies for the treatment of this disease, this study was designed to investigate the contribution of these markers to airway inflammation. The present study included 25 children with asthma and 15 control children. The asthma cases were 18 males and 7 females ( mean age= 9.36 ± 2.16 years). According to the severity of asthma, patients were classified as mild (n=10), moderate (n=9) and severe (n=6) asthma. They were further classified into allergic asthmatics (extrinsic atopic, n=10) and non-allergic (intrinsic asthmatics, n=15). Estimations of serum levels of IL-8, sICAM-1(by ELISA) and ECP (by flouroimmunoassay) were done. The results of this study revealed that serum levels of IL-8 were significantly higher in asthmatics than in controls. Also, serum levels of it were significantly higher in cases with severe and cases with moderate asthma than in cases with mild asthma. Serum levels of sICAM-1 were significantly higher in asthmatic than in control children, in severe than in moderate, and in both than in mild asthma cases. Levels of ECP were significantly higher in asthmatics than in controls. Also, serum levels of it were related to asthma severity. Furthermore, the three biomarkers showed higher expression in allergic asthmatics versus non- allergies. There were positive correlations of IL-8, sICAM-1, ECP and IgE with each other in asthmatic children that may indicate interaction of these markers in regulation and persistence of inflammatory cascade in asthma through different mechanisms. In

Mid-trimester amniotic fluid concentrations of the proinflammatory cytokines IL-6, IL-8, TNF-α, and lipopolysaccharide binding protein in normal pregnancies: a prospective evaluation according to parity, gestational age, and fetal gender.

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Bamberg, Christian; Fotopoulou, Christina; Linder, Mattea; Roehr, Charles Christoph; Dudenhausen, Joachim W; Henrich, Wolfgang; Kalache, Karim

2011-07-01

To assess mid-trimester amniotic fluid concentrations of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and lipopolysaccharide binding protein (LBP) in pregnancies with normal outcome and correlate them with gestational week (GW), parity, and fetal gender. Cytokine concentrations were measured within a week of amniocentesis during GW 15+0 to 20+6 and correlated with GW at birth, parity, and fetal gender. After exclusion of women with an adverse pregnancy outcome or those lost to follow-up, 273 consecutive patients were evaluated (median parity: 1; range: 0-5). Ranges for IL-6, IL-8, TNF-α, and LBP were 4.9-2620 pg/mL, 36.2-5843 pg/mL, 8.0-28.2 pg/mL, and 0.06-1.9 μg/mL, respectively. IL-6, IL-8, and LBP values did not respectively differ among time points, but TNF-α values did between the 15(th) and 16(th) and the 15(th) and 18(th) weeks of gestation (Pparity or fetal gender were identified. Cytokine concentrations in amniotic fluid during the mid-trimester did not differ with parity or fetal gender. IL-6, IL-8, and LBP levels appeared stable with GW, whereas GW significantly influenced TNF-α concentrations. Further analyses are warranted to establish the role of cytokines in predicting adverse pregnancy outcomes.

Effects of interleukin-8 on estradiol and progesterone production by bovine granulosa cells from large follicles and progesterone production by luteinizing granulosa cells in culture.

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Shimizu, Takashi; Kaji, Ayami; Murayama, Chiaki; Magata, Fumie; Shirasuna, Koumei; Wakamiya, Kaori; Okuda, Kiyoshi; Miyamoto, Akio

2012-01-01

Interleukin 8 (IL-8) is a chemoattractant involved in the recruitment and activation of neutrophils and is associated with the ovulate process. We examined the possible role of IL-8 in steroid production by bovine granulosa cells before and after ovulation. The concentration of IL-8 in the follicular fluid of estrogen-active dominant (EAD) and pre-ovulatory follicles (POF) was higher than that of small follicles (SF). CXCR1 mRNA expression was higher in the granulosa cells of EAD and POF than that of SF. In contrast, CXCR2 mRNA expression was lower in granulosa cells of EAD and POF than in SF. IL-8 inhibited estradiol (E2) production in follicle-stimulating hormone (FSH)-treated granulosa cells at 48 h of culture. IL-8 also suppressed CYP19A1 mRNA expression in FSH-treated granulosa cells. IL-8 stimulated progesterone (P4) production in luteinizing hormone (LH)-treated granulosa cells at 48 h of culture. Although IL-8 did not alter the expression of genes associated with P4 production, it induced StAR protein expression in LH-treated granulosa cells. The expression of CXCR1 mRNA in corpus luteum (CL) did not change during the luteal phase. In contrast, the expression of CXCR2 mRNA in middle CL was significantly higher than in early and regression CL during the luteal phase. In luteinizing granulosa cells, an in vitro model of granulosa cell luteinization, CXCR2 mRNA expression was downregulated, whereas CXCR1 mRNA expression was unchanged. IL-8 also stimulated P4 production in luteinizing granulosa cells. These data provide evidence that IL-8 functions not only as a chemokine, but also act as a regulator of steroid synthesis in granulosa cells to promote luteinization after ovulation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Antiphospholipid antibody-induced miR-146a-3p drives trophoblast interleukin-8 secretion through activation of Toll-like receptor 8.

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Gysler, Stefan M; Mulla, Melissa J; Guerra, Marta; Brosens, Jan J; Salmon, Jane E; Chamley, Lawrence W; Abrahams, Vikki M

2016-07-01

What is the role of microRNAs (miRs) in antiphospholipid antibody (aPL)-induced trophoblast inflammation? aPL-induced up-regulation of trophoblast miR-146a-3p is mediated by Toll-like receptor 4 (TLR4), and miR-146a-3p in turn drives the cells to secrete interleukin (IL)-8 by activating the RNA sensor, TLR8. Obstetric antiphospholipid syndrome (APS) is an autoimmune disorder characterized by circulating aPL and an increased risk of pregnancy complications. We previously showed that aPL recognizing beta2 glycoprotein I (β2GPI) elicit human first trimester trophoblast secretion of IL-8 by activating TLR4. Since some miRs control TLR responses, their regulation in trophoblast cells by aPL and functional role in the aPL-mediated inflammatory response was investigated. miRs can be released from cells via exosomes, and therefore, miR exosome expression was also examined. A panel of miRs was selected based on their involvement with TLR signaling: miR-9; miR-146a-5p and its isomiR, miR-146a-3p; miR-155, miR-210; and Let-7c. Since certain miRs can activate the RNA sensor, TLR8, this was also investigated. For in vitro studies, the human first trimester extravillous trophoblast cell line, HTR8 was studied. HTR8 cells transfected to express a TLR8 dominant negative (DN) were also used. Plasma was evaluated from pregnant women who have aPL, either with or without systemic lupus erythematous (SLE) (n = 39); SLE patients without aPL (n = 30); and healthy pregnant controls (n = 20). Trophoblast HTR8 wildtype and TLR8-DN cells were incubated with or without aPL (mouse anti-human β2GPI mAb) for 48-72 h. HTR8 cells were also treated with or without aPL in the presence and the absence of a TLR4 antagonist (lipopolysaccharide from Rhodobacter sphaeroides; LPS-RS), specific miR inhibitors or specific miR mimics. miR expression levels in trophoblast cells, trophoblast-derived exosomes and exosomes isolated from patient plasma were measured by qPCR. Trophoblast IL-8 secretion was

The influence of adhesin protein from Aggregatibacter actinomycetemcomitans on IL-8 and MMP-8 titre in aggressive periodontitis

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Rini Revijanti Ridwan

2015-03-01

Full Text Available Background: Adhesion can actually be considered as a part of both a powerful survival mechanism and a virulence mechanism for bacterial pathogens. Bacterial adhesin is an instrument for bacteria to do invasion to host. Bacterial adhesin depends on ligand interaction as a signaling mediator that will influence invasion and increase pro and anti-inflammatory because of the influence of the receptors of innate immune response. Aggregatibacter actimycetemcomitans has fimbriae included in type IV pili containing mostly with protein weighed 6.5 kDa and at least with protein weighed 54 kDa. Purpose: The purpose of this research is to analyze the influence of the induction of adhesin protein derived from A. actinomycetemcomitans on IL-8 and MMP-8 titre of Wistar rats. Methods: Adhesin protein derived from A. actinomycetemcomitans weighed 24 kDa was induced on the maxillary first molar sulcus of Wistar rats to prove that adhesin protein could affect IL-8 and MMP-8 titre. Next, to determine its influence, Elisa technique was conducted. Results: It is known that the levels of IL-8 and MMP-8 titre were increased in the group induced with adhesin protein derived from A. actinomycetemcomitans compared with the control group. Conclusion: It can be concluded that adhesin protein derived from A. actinomycetemcomitans can cause alveolar bone damage through the increasing levels of IL-8 and MMP-8 in aggressive periodontitis.

Clinical significance of measurement of serum NO, IL-6 and IL-8 levels after treatment in patients with schizophrenia

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Gao Wanqin

2010-01-01

Objective: To study the significance of changes of serum NO, IL-6 and IL-8 levels after treatment in patients with schizophrenia. Methods: Serum IL-6, IL-8 (with RIA) and NO (with bio-chemistry) levels were determined in 37 patients with schizophrenia both before and after treatment as well as in 35 controls. Results: Before treatment, the serum IL-6, IL-8 levels in the patients were significantly higher than those in controls (P<0.01). While the serum NO levels were significantly lower (P<0.01). After six weeks' treatment, the levels of IL-6, IL-8 in the patients, though dropped markedly still remained significantly higher (P<0.05) than those in controls. The serum NO levels, though markedly increased after treatment, were still remained significantly lower than those in the controls (P<0.05). Conclusion: Serum NO, IL-6 and IL-8 levels were closely related to the diseases process of schizophrenia and were of prognostic values. (authors)

Behavioural consequences of an 8 Gy total body irradiation in mice: Regulation by interleukin-4

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Van der Meeren, A.; Lebaron-Jacobs, L.

2001-01-01

The effects of an 8 Gy γ total body irradiation (TBI) on exploration and locomotion activities as well as temperature were studied in C57BL6/J mice. Survival, body weight, and blood cell counts were also assessed in irradiated mice treated with placebo or interleukin (IL)-4. The efficacy of IL-4 treatment on improvement in exploration activity was evaluated. The study was carried out from 3 h to 30 days following exposure. Our results showed a biphasic response to irradiation concerning the exploration activity of mice. Irradiated mice had reduced activity as early as 3 h after exposure, with recovery of activity within 24 h. The exploration activity again decreased 4 days after irradiation and the recovery occurred slowly after day 17. IL-4 ameliorated the exploration status in mice in both phases. The locomotion activity was studied using a telemetry apparatus. A similar pattern to that of the exploration data was observed, with a minimal activity observed between days 13 and 17. A radiation-induced hypothermia was also noticed over the same time period. (author)

Behavioural consequences of an 8 Gy total body irradiation in mice: Regulation by interleukin-4

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Van der Meeren, A.; Lebaron-Jacobs, L. [Inst. de Protection et de Surete Nucleaire, Dept. de Protection de la sante de l' Homme et de Dosimetrie, Section Autonome de Radiobiologie Appliquee a la Medecine, IPSN, Fontenay-aux-Roses (France)

2001-02-01

The effects of an 8 Gy {gamma} total body irradiation (TBI) on exploration and locomotion activities as well as temperature were studied in C57BL6/J mice. Survival, body weight, and blood cell counts were also assessed in irradiated mice treated with placebo or interleukin (IL)-4. The efficacy of IL-4 treatment on improvement in exploration activity was evaluated. The study was carried out from 3 h to 30 days following exposure. Our results showed a biphasic response to irradiation concerning the exploration activity of mice. Irradiated mice had reduced activity as early as 3 h after exposure, with recovery of activity within 24 h. The exploration activity again decreased 4 days after irradiation and the recovery occurred slowly after day 17. IL-4 ameliorated the exploration status in mice in both phases. The locomotion activity was studied using a telemetry apparatus. A similar pattern to that of the exploration data was observed, with a minimal activity observed between days 13 and 17. A radiation-induced hypothermia was also noticed over the same time period. (author)

Clinical significance of the changes of serum IL-8 and IL-12 levels in pediatric patients with anaphylactoid purpura (AP)

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Liang Zhenming; Liu Xia

2005-01-01

Objective: To explore the role of IL-8 and IL-12 in the pathogenesis of anaphylactoid purpura (AP) and anaphylactoid purpura nephritis (APN). Methods: Serum IL-8 (with RIA) and IL-12 (with ELISA) levels were measured in 32 pediatric patients with anaphylactoid purpura (AP), 11 pediatric patients with anaphylactoid purpura nephritis (APN) and 15 controls. Results: During acute stage, serum IL-8 and IL-12 levels in both the AP and APN patients were significantly higher than those in controls and remained higher during convalescence. IL-8 and IL-12 levels were mutually positively correlated in acute stage. Conclusion: IL-8 and IL-12 participated in the pathogenesis of AP and APN. Theoretically, antagonist to those cytokines might be of clinical benefits. (authors)

THE CHANGES IN LEVEL OF 8-ENDORPHIN, INTERLEUKIN-2, INTERLEUKIN-4, INTERLEUKIN-6, IMUNOGLOBULIN AND CORTISOL HORMONE ON PRACTICES OF BRETHING EXERCISE

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Rumpis Agus Sudarku

2012-11-01

Full Text Available Background: the study was to reveal the changes of immunity at breathing exercises. This was an experimental study. With randomized pre-posttest control group design. Methods: The population were students of MA Mu'alimin, in Yogyakarta. Respondents were 15 students for each groups. The unit analysis were data analysis from blood taken from vena cubiti. The dependent variables were levels of IL 6, IL 4, IL 2, cortisol, Beta Endorphin, and lgG. The training programme was conducted in 7 weeks, 3 times per week, sub maximal intensity, and 6 sets per session. The laboratory vanable were the ELISA method. Results: Manova test were p: 0,000 Implied that there were differences (Wilk Lambda pinterleukin 6 (0.367 while the other variables had less significant relation. Discriminator variables representing the function contributed to every discriminator of modulation immunity were beta endorphin, interleukin 6 and interleukin 4. Hence, beta endorphin had the strongest contribution to the increase of body immunity compared with other variables. Conclusion: Breathing exercises could increase physical fitness and impenetrability of proven body manifestly. Breathing exercise increased beta endorphin, immunoglobulin G and interleukin 6, while interleukin 2 and interleukin 4 did not increase Cortisol level did not decrease stgnificantly but there was an indication of level of cortisol decrease. Immunity modulator which caused breathing exercise stressor got by 3 groups with strong contribution on the basis concept of psychoneuroimmunologic. Key words: breathing exercise, immunity, modulation

Modulation of Interleukin-8 and staphylococcal flora by Avène hydrotherapy in patients suffering from chronic inflammatory dermatoses.

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Casas, C; Ribet, V; Alvarez-Georges, S; Sibaud, V; Guerrero, D; Schmitt, A-M; Redoulès, D

2011-02-01

A number of studies argue in favour of an important role of microbial colonization, in particular of Staphylococcus aureus, in triggering atopic dermatitis (AD) flare-up and psoriasis, in particular through the superantigenic properties of toxins generated by S. aureus. The aim of this study was to assess the efficacy of a 3-week Avène hydrotherapy on the skin surface of patients suffering from psoriasis or atopic dermatitis. Skin samples were taken from healthy subjects or atopic (n = 18) or psoriatic patients (n = 39) undergoing hydrotherapy at Avène at the beginning (D0) and the end of treatment (D18). The severity of the dermatosis was evaluated according to SCORing Atopic Dermatitis (SCORAD) or Psoriasis Area Severity Index (PASI) scores at D0 and D18. Marker of inflammation interleukin 8 (IL-8), S. aureus colonization (protein A) and enterotoxins were assessed in skin samples using RT-PCR. At D0, significant differences were observed between healthy subjects and atopic or psoriatic patients in all the parameters evaluated (IL-8, protein A). At the end of the hydrotherapy, a significant decrease in SCORAD was associated with a significant reduction of IL-8, S. aureus colonization and enterotoxin D in patients with atopic dermatitis. Similarly, a significant decrease in PASI was associated with a significant reduction of IL-8, S. aureus colonization and enterotoxin N in patients with psoriasis. This study demonstrates the positive effects of Avène hydrotherapy on the skin of patients suffering from chronic dermatosis, with decreased inflammation and reduced colonization by S. aureus. © 2010 The Authors. JEADV © 2010 European Academy of Dermatology and Venereology.

Expression of interleukine-8 as an independent prognostic factor for sporadic colon cancer dissemination.

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Nastase, A; Paslaru, L; Herlea, V; Ionescu, M; Tomescu, D; Bacalbasa, N; Dima, S; Popescu, I

2014-06-15

The aim of our study was to investigate the gene and serum protein expression profiles of IL-8 in colon cancer and associated hepatic metastasis and to correlate these results with clinicopathologic variables of the patients. IL-8 was evaluated by qPCR and ELISA in a total number of 62 colon cancer patients (n=42 by qPCR and n=20 by ELISA) in normal and tumoral tissue specimens and serum samples respectively. Additionally synchronous metastasis from 5 of these patients were also collected at the time of surgery and analyzed by qPCR. IL-8 was up regulated in all analyzed tumoral samples compared with normal tissue (P-value = 0.01) and higher expressed in metastatic tissues compared with tumoral tissues (P -value= 0.03). The median expression of IL-8 in patients over 60 years old was found to be higher compared with the median expression of IL8 in patients less than 60 years old (3.89 compared with 14.69, P -value= 0.005). According to tumor grading, we found that IL-8 in tumors with well differentiated adenocarcinoma have a median mRNA expression of 9.78 compared with a median mRNA IL8 expression of 26.63 in moderate or poor differentiated adenocarcinoma. Levels of IL-8 determined in serum were statistically significant correlated with preoperative carcinoembryonic antigen level (P -value= 0.003, R=0.57) and with distant metastasis (P-value =0.008). Serum level of IL-8 increased proportionally along with TNM tumor stage and was found to be statistically significant correlated with C-reactive protein (P -value, R=0.64). Colon cancer patients had higher IL-8 levels as determined by ELISA (median value= 29.64 pg/ml) compared with healthy controls (median value= 4.86 pg/ml). Our results provide additional support for the role of inflammation in colon cancer and indicate that IL-8 could be further validated in association with other already used markers for prognostic and diagnostic of evolutional disease in colon cancer patients.

The effect of Candida albicans on the expression levels of toll-like receptor 2 and interleukin-8 in HaCaT cells under High- and Low-glucose conditions

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Di Wang

2018-01-01

Full Text Available Background: The diabetics are prone to skin infections, especially with Candida albicans. It is important to elucidate the different antifungal abilities of patients with hyperglycemia and healthy controls for the treatment of this condition. The toll-like receptor 2 (TLR2 and interleukin (IL-8 secreted by keratinocytes counteract C. albicans. Aim: This study aims to explore the differential expression of toll-like receptor 2 (TLR2 and interleukin (IL-8 secretion by keratinocytes between controls and diabetic patients when challenged with C. albicans. Materials and Methods: HaCaT cells were cultured in high-glucose (HG Dulbecco's modified Eagle's medium (DMEM and low-glucose (LG DMEM. Then, they were exposed to C. albicans hyphae for 24 h. The expression levels of TLR2 and IL-8 were determined at different periods in both the HG and LG groups. Real-time polymerase chain reaction analysis, western blotting, and enzyme-linked immunosorbent assays were performed in this study. The morphological changes of HaCaT cells under two different glucose concentrations were also observed. Results: We found that the expression levels of both TLR2 and IL-8 increased and then decreased in the two groups. Notably, the IL-8 levels in the LG group were higher than those in the HG group at each time point (P<0.05, and the TLR2 levels in the LG group were higher than those in the HG group at the beginning of the experiment and after 24 h of treatment with C. albicans (P<0.05. In each group, the levels of IL-8 and TLR2 at the secretion peak were significantly different from those in the initial and the last period of observation (P<0.05. The cellular morphology of HaCaT cells treated with different concentrations of glucose was also similar. However, with prolonged coculture time, cell death increased. Conclusion: These observations showed that TLR2 and IL-8 act on the keratinocytes interacting with C. albicans, and HG status might affect the function of HaCaT cells

Influence of different thyroid functional statuses on human serum IL-8, TNF levels

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Wei Feng; Jiao Yanxiang; Guang Yancen; Zhang Zhu; Wei Cuiying

2003-01-01

Objective: To evaluate the effect of different statuses of thyroid function (hyperthyroidism and hypothyroidism as well as euthyroid status) on serum IL-8, TNF levels. Methods: Serum IL-8, TNF levels of 95 hyperthyroidism patients (41 males, 54 females), 53 hypothyroidism patients (23 males, 30 females), 45 euthyroid controls (24 males, 21 females) were measured with RIA. Results: 1. Serum IL-8 levels in hyperthyroidism (Graves' disease) patients were significantly higher than those in controls. (F=2.93, p 0.05). IL-8 and TNF levels were also not correlated to age and thyroid hormone levels. Conclusion: Both IL-8 and TNF took part in many auto-immure pathological processes including hyper-and hypo-thyroidism

Possible identity of IL-8 converting enzyme in human fibroblasts as a cysteine protease.

Science.gov (United States)

Ohashi, Kensaku; Sano, Emiko; Nakaki, Toshio; Naruto, Masanobu

2003-04-01

A converting activity was characterized in human diploid fibroblasts, which secrete 72IL-8 and 77IL-8 in treatment with IFN-beta and poly I: poly C. 77IL-8 was significantly converted to 72IL-8 by a partially purified fraction of the culture supernatant of human diploid fibroblasts. The converting activity, which was temperature-dependent and optimal at pH 6, was completely inhibited by cysteine protease inhibitors, antipain dihydrochloride and E-64, but not by other types of protease inhibitors. These data clearly show that human diploid fibroblasts are capable of processing IL-8 to produce a mature IL-8 and that the putative converting enzyme appears to be a cysteine protease.

Relations Between Serum Essential Fatty Acids, Cytokines (IL-6 & IL ...

African Journals Online (AJOL)

The aim of this study was to investigate the relations between free radical generation, interleukins (IL-6 & IL-8), apoptotic marker soluble Fas (sFas), and the level of ... IL-6, IL-8 and sFas whereas serum fatty acid revealed that Linoleicacid (LA) and alpha linolenic acid (ALA) were significantly decreased in the studied cases .

Skin sensitizer identification by IL-8 secretion and CD86 expression on THP-1 cells.

Science.gov (United States)

Parise, Carolina Bellini; Sá-Rocha, Vanessa Moura; Moraes, Jane Zveiter

2015-12-25

Substantial progress has been made in the development of alternative methods for skin sensitization in the last decade in several countries around the world. Brazil is experiencing an increasing concern about using animals for product development, since the publication of the Law 9605/1998, which prohibits the use of animals when an alternative method is available. In this way, an in vitro test to evaluate allergenic potential is a pressing need.This preliminary study started setting the use of myelomonocytic THP-1 cell line, according to the human cell line activation test (h-CLAT), already under validation process. We found that 48-h chemical exposure was necessary to identify 22 out of 23 sensitizers by the analyses of CD86 expression. In addition, the CD54 expression analyses presented a poor efficiency to discriminate sensitizers from non-sensitizers in our conditions. In view of these results, we looked for changes of pro-inflammatory interleukin profile. The IL-8 secretion analyses after 24-h chemical incubation seemed to be an alternative for CD54 expression assessing.Altogether, our findings showed that the combination of the analyses of CD86 expression and IL-8 secretion allowed predicting allergenicity.

Role of p38 MAPK in the selective release of IL-8 induced by chemical allergen in naive THp-1 cells.

Science.gov (United States)

Mitjans, Montserrat; Viviani, Barbara; Lucchi, Laura; Galli, Corrado L; Marinovich, Marina; Corsini, Emanuela

2008-03-01

At present, the assessment of the allergenic potential of chemicals is carried out using animal models. Over the last decade, several in vitro methods mainly using primary dendritic cells have been proposed to identify the potential of chemicals to induce skin sensitization to meet current animal welfare and public opinions. The major limitations of such tests are the donor-to-donor variability, the low levels in the source, and a possible shortage of human sources. The aim of the present investigation was to establish an in vitro test to identify chemical allergens using the human promyelocytic cell line THP-1 in order to avoid some of these difficulties. We investigated whether the chemokine interleukin-8 or CXCL8 (IL-8) production could provide a methodology for the detection of both respiratory and contact allergens. THP-1 cells were exposed to contact allergens (cinnamaldehyde, dinitrochlorobenzene, nickel sulfate, penicillin G, p-phenylenediamine, tetramethylthiuram disulfide), to respiratory allergens (ammonium hexachloroplatinate, diphenylmethane diisocyanate, trimellitic anhydride) and to irritants (salicylic acid, phenol, sodium lauryl sulphate). Following 48 h of incubation, the release of IL-8 was evaluated by sandwich ELISA. IL-8 production was significantly increased after stimulation with all allergens tested, with the exception of trimellitic anhydride, whereas irritants exposure failed to induce IL-8 release. The lack of IL-8 production by trimellitic anhydride can be explained by the rapid hydrolysis of this chemical in water to trimellitic acid, which is not an allergen. In contrast to IL-8 release, CD54 and CD86 expression did not provide a sensitive method failing to correctly identify approximately 30% of the tested compounds. Although CD86 appears to be a more sensitive marker than CD54 when discriminating allergens from irritants neither of these markers provided robust methodology. We also investigated if a common activation pathway in

IL-17-Expressing CD4+ and CD8+ T Lymphocytes in Human Toxoplasmosis

Directory of Open Access Journals (Sweden)

Jéssica Líver Alves Silva

2014-01-01

Full Text Available This study aimed to measure the synthesis of Th1 and Th2 cytokines by mononuclear cells after culture with live T. gondii and identified Th17 (CD4+ and Tc17 (CD8+ cells in toxoplasma-seronegative and toxoplasma-seropositive parturient and nonpregnant women. Cytometric bead arrays were used to measure cytokine levels (IL-2, TNF-α, IFN-γ, IL-4, IL-5, and IL-10; immunophenotyping was used to characterize Th17 and Tc17 cells, and the cells were stained with antibodies against CD4+ and CD8+ T cells expressing IL-17. The addition of tachyzoites to cell cultures induced the synthesis of IL-5, IL-10, and TNF-α by cells from seronegative parturient women and of IL-5 and IL-10 by cells from seropositive, nonpregnant women. We observed a lower level of IL-17-expressing CD4+ and CD8+ T lymphocytes in cultures of cells from seronegative and seropositive parturient and nonpregnant women that were stimulated with tachyzoites, whereas analysis of the CD4+ and CD8+ T cell populations showed a higher level of CD4+ T cells compared with CD8+ T cells. These results suggest that the cytokine pattern and IL-17-expressing CD4+ and CD8+ T lymphocytes may have important roles in the inflammatory response to T. gondii, thus contributing to the maintenance of pregnancy and control of parasite invasion and replication.

Nebulized hypertonic saline decreases IL-8 in sputum of patients with cystic fibrosis.

LENUS (Irish Health Repository)

Reeves, Emer P

2011-06-01

Inflammation within the cystic fibrosis (CF) lung is mediated by inflammatory chemokines, such as IL-8. IL-8 is protected from proteolytic degradation in the airways by binding to glycosaminoglycans, while remaining active. Evidence that increased hypertonicity of airway secretions induced by hypertonic saline treatment alters levels of IL-8 is lacking.

CD8+ T Cells Mediate Female-Dominant IL-4 Production and Airway Inflammation in Allergic Asthma.

Directory of Open Access Journals (Sweden)

Chihiro Ito

Full Text Available The prevalence and severity of bronchial asthma are higher in females than in males after puberty. Although antigen-specific CD8+ T cells play an important role in the development of asthma through their suppressive effect on cytokine production, the contribution of CD8+ T cells to sex differences in asthmatic responses remains unclear. In the present study, we investigated the sex-specific effect of CD8+ T cells in the suppression of asthma using an ovalbumin mouse model of asthma. The number of inflammatory cells in bronchoalveolar lavage (BAL fluid, lung type 2 T-helper cytokine levels, and interleukin-4 (IL-4 production by bronchial lymph node cells were significantly higher in female wild-type (WT mice compared with male mice, whereas no such sex differences were observed between male and female cd8α-disrupted mice. The adaptive transfer of male, but not female, CD8+ T cells reduced the number of inflammatory cells in the recovered BAL fluid of male recipient mice, while no such sex difference in the suppressive activity of CD8+ T cells was observed in female recipient mice. Male CD8+ T cells produced higher levels of IFN-γ than female CD8+ T cells did, and this trend was associated with reduced IL-4 production by male, but not female, CD4+ T cells. Interestingly, IFN-γ receptor expression on CD4+ T cells was significantly lower in female mice than in male mice. These results suggest that female-dominant asthmatic responses are orchestrated by the reduced production of IFN-γ by CD8+ T cells and the lower expression of IFN-γ receptor on CD4+ T cells in females compared with males.

CD4(+) T cells producing interleukin (IL)-17, IL-22 and interferon-? are major effector T cells in nickel allergy

DEFF Research Database (Denmark)

Dyring Andersen, Beatrice; Skov, Lone; Løvendorf, Marianne B

2013-01-01

the frequencies of CD4(+) , CD8(+) and γδ T cells producing IL-17, IL-22 and interferon (IFN)-γ in the blood and skin from nickel-allergic patients. Patients/materials/methods Blood samples were collected from 14 patients and 17 controls, and analysed by flow cytometry. Biopsies were taken from 5 patients and 6......-allergic patients, there was massive cellular infiltration dominated by CD4(+) T cells producing IL-17, IL-22 and IFN-γ in nickel-challenged skin but not in vehicle-challenged skin. Conclusion CD4(+) T cells producing IL-17, IL-22 and IFN-γ are important effector cells in the eczematous reactions of nickel......Background It has been suggested that interleukin (IL)-17 and IL-22 play important roles in the elicitation of human allergic contact dermatitis; however, the frequencies of T cell subtypes producing IL-17 and IL-22 in human allergic contact dermatitis are unknown. Objectives To determine...

The diagnostic value of CRP, IL-8, PCT, and sTREM-1 in the detection of bacterial infections in pediatric oncology patients with febrile neutropenia

NARCIS (Netherlands)

Miedema, Karin G. E.; de Bont, Eveline S. J. M.; Elferink, Rob F. M. Oude; van Vliet, Michel J.; Nijhuis, Claudi S. M. Oude; Kamps, Willem A.; Tissing, Wim J. E.

2011-01-01

In this study, we evaluated C-reactive protein (CRP), interleukin (IL)-8, procalcitonin (PCT), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as predictors for bacterial infection in febrile neutropenia, plus their usefulness in febrile neutropenia during chemotherapy-induced

MFGE8 inhibits inflammasome-induced IL-1β production and limits postischemic cerebral injury.

Science.gov (United States)

Deroide, Nicolas; Li, Xuan; Lerouet, Dominique; Van Vré, Emily; Baker, Lauren; Harrison, James; Poittevin, Marine; Masters, Leanne; Nih, Lina; Margaill, Isabelle; Iwakura, Yoichiro; Ryffel, Bernhard; Pocard, Marc; Tedgui, Alain; Kubis, Nathalie; Mallat, Ziad

2013-03-01

Milk fat globule-EGF 8 (MFGE8) plays important, nonredundant roles in several biological processes, including apoptotic cell clearance, angiogenesis, and adaptive immunity. Several recent studies have reported a potential role for MFGE8 in regulation of the innate immune response; however, the precise mechanisms underlying this role are poorly understood. Here, we show that MFGE8 is an endogenous inhibitor of inflammasome-induced IL-1β production. MFGE8 inhibited necrotic cell-induced and ATP-dependent IL-1β production by macrophages through mediation of integrin β(3) and P2X7 receptor interactions in primed cells. Itgb3 deficiency in macrophages abrogated the inhibitory effect of MFGE8 on ATP-induced IL-1β production. In a setting of postischemic cerebral injury in mice, MFGE8 deficiency was associated with enhanced IL-1β production and larger infarct size; the latter was abolished after treatment with IL-1 receptor antagonist. MFGE8 supplementation significantly dampened caspase-1 activation and IL-1β production and reduced infarct size in wild-type mice, but did not limit cerebral necrosis in Il1b-, Itgb3-, or P2rx7-deficient animals. In conclusion, we demonstrated that MFGE8 regulates innate immunity through inhibition of inflammasome-induced IL-1β production.

Ursodeoxycholic acid inhibits TNFα-induced IL-8 release from monocytes.

Science.gov (United States)

O'Dwyer, Aoife M; Lajczak, Natalia K; Keyes, Jennifer A; Ward, Joseph B; Greene, Catherine M; Keely, Stephen J

2016-08-01

Monocytes are critical to the pathogenesis of inflammatory bowel disease (IBD) as they infiltrate the mucosa and release cytokines that drive the inflammatory response. Ursodeoxycholic acid (UDCA), a naturally occurring bile acid with anti-inflammatory actions, has been proposed as a potential new therapy for IBD. However, its effects on monocyte function are not yet known. Primary monocytes from healthy volunteers or cultured U937 monocytes were treated with either the proinflammatory cytokine, TNFα (5 ng/ml) or the bacterial endotoxin, lipopolysaccharide (LPS; 1 μg/ml) for 24 h, in the absence or presence of UDCA (25-100 μM). IL-8 release into the supernatant was measured by ELISA. mRNA levels were quantified by qPCR and changes in cell signaling proteins were determined by Western blotting. Toxicity was assessed by measuring lactate dehydrogenase (LDH) release. UDCA treatment significantly attenuated TNFα-, but not LPS-driven, release of IL-8 from both primary and cultured monocytes. UDCA inhibition of TNFα-driven responses was associated with reduced IL-8 mRNA expression. Both TNFα and LPS stimulated NFκB activation in monocytes, while IL-8 release in response to both cytokines was attenuated by an NFκB inhibitor, BMS-345541. Interestingly, UDCA inhibited TNFα-, but not LPS-stimulated, NFκB activation. Finally, TNFα, but not LPS, induced phosphorylation of TNF receptor associated factor (TRAF2), while UDCA cotreatment attenuated this response. We conclude that UDCA specifically inhibits TNFα-induced IL-8 release from monocytes by inhibiting TRAF2 activation. Since such actions would serve to dampen mucosal immune responses in vivo, our data support the therapeutic potential of UDCA for IBD. Copyright © 2016 the American Physiological Society.

Clinical significance of determination of semen plasma IL-2, IL-6, IL-8 and TNF-α contents in infertile males

International Nuclear Information System (INIS)

Sun Baoyi; Li Jun; Zhang Jiyun

2004-01-01

Objective: To explore the influence of high semen plasma contents of the cytokines (IL-2, IL-6, IL-8, TNF-α) on male fertility. Methods: Semen plasma levels of IL-2, IL-6, IL-8, and TNF-α were determined with RIA in 126 infertile and 20 fertile males. Results: Semen plasma contents of the 4 cytokines in infertile subjects were significantly higher than those in fertile ones (p 4/HP, n=15) had significantly higher contents of cytokines than those without leucocytospermia (WBC<4/HP, n=111). Besides, TNF-α contents in subjects with lower sperm activity and less motility rate as well as IL-8 contents in subjects with less sperm motility rate were both significantly higher than those in subjects with more normal sperms (p<0.01, p<0.05). Conclusion: High semen plasma cytokines contents represent existing local infection and enhanced auto-immune status, both damaging to sperms. Infertility would be the inevitable consequence. Monitoring of changes of the cytokine contents should be a part of fertility studies

Inhibition of Lipopolysaccharide-Induced Interleukin 8 in Human Adenocarcinoma Cell Line HT-29 by Spore Probiotics: B. coagulans and B. subtilis (natto).

Science.gov (United States)

Azimirad, Masoumeh; Alebouyeh, Masoud; Naji, Tahereh

2017-03-01

Probiotics are used as a treatment for different intestinal disorders. They confer health benefits by different ways. This study was aimed to investigate immunomodulatory effect of Bacillus probiotic spores on the production of lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) in HT-29 intestinal epithelial cells. Differentiated intestinal epithelial cell line was used as a model for the study of colonization of purified spores (Bacillus subtilis (natto) and B. coagulans) and their anti-inflammatory effects. MTT assay and trypan blue staining were used for the detection of optimal concentration of the purified spores and LPS. Pre-treatment assay was done by treatment of the cells with the purified spores for 2 h, followed by challenges with LPS for 3 and 18 h. Post-treatment assay was done by initial treatment of the cells with LPS for 18 h, followed by the spores for 3 and 6 h. Levels of IL-8 secretion and its mRNA expression were measured by ELISA and relative Q real-time PCR. Our results showed similar rates of adherence to intestinal epithelial cells by the spore probiotics, while displaying no cytotoxic effect. In the pre-treatment assay, a significant decrease in IL-8, at both protein and mRNA levels, was measured for B. coagulans spores after the addition of LPS, which was higher than those observed for Bacillus subtilis (natto) spores. In the post-treatment assay, while Bacillus subtilis (but not B. coagulans) diminished the LPS-stimulated IL-8 levels after 3 h of incubation, the inhibitory effect was not constant. In conclusion, ability of Bacillus spore probiotics for adherence to intestinal epithelial cell and their anti-inflammatory effects, through interference with LPS/IL-8 signaling, was shown in this study. Further studies are needed to characterize responsible bacterial compounds associated with these effects.

Detection of experimental infections with 99mTc-labeled monoclonal antibodies against TNF-α and interleukin-8

International Nuclear Information System (INIS)

Welling, Mick; Feitsma, Hans I.J.; Calame, Wim; Pauwels, Ernest K.J.

1997-01-01

This study was designed to assess monoclonal antibodies (MAbs) directed against tumor necrosis factor-α (TNF-α) (anti-TNF) or interleukin-8 (anti-IL-8) as radioactive agents for the detection of Staphylococcus aureus- or Klebsiella pneumoniae-infected thighs in mice. At 5 min (acute infection) or 20 h (established) post-infection, 20 μg of the 99m Tc-labeled MAbs were injected. At various time intervals, the accumulation of the radiotracer in the infected thighs was assessed and expressed as a target-to-nontarget (T/NT) ratio. The binding of 99m Tc-labeled MAbs to circulating mononuclear cells and granulocytes was quantitated 20 h after injection. The pharmacokinetics of the MAbs, in relation to the control agents 99m Tc-labeled polyclonal human immunoglobulin (IgG) and a 99m Tc-labeled nonspecific IgG1 MAb, were also studied. In acute infections, 99m Tc-anti-TNF accumulated to a higher extent (p 99m Tc-IgG and was higher at 0.25 h in K. pneumoniae-infected mice (p 99m Tc-IgG. In established S. aureus and K. pneumoniae infections, 99m Tc-anti-IL-8 detected the infection more intensely than 99m Tc-IgG until 1 h after injection. In both S. aureus and K. pneumoniae infections, localization of sites of infection correlates (p 99m Tc-labeled MAbs to granulocytes and mononuclear cells in both acute and established infections. It was concluded that 99m Tc-labeled MAbs, directed against TNF-α and IL-8, accumulate in bacterial infections in mice to a higher extent than does 99m Tc-IgG after infection and is related to the binding of the antibodies to blood leukocytes. With these 99m Tc-labeled MAbs, information might be gained about the development of an infection

IL-8、 MMP-9、 INF-γ的检测对结核性脑膜炎及病毒性脑膜炎发病的意义%Detection of interleukin-8, matrix metalloproteinase-9 and interferon gamma levels in the cerebrospinal fluid of patients with tuberculous meningitis and viral meningitis

Institute of Scientific and Technical Information of China (English)

朱飞; 张家堂; 邢小微; 贺路星; 赵威; 郎森阳; 于生元

2012-01-01

目的 探讨脑脊液中白细胞介素-8(IL-8)、基质金属蛋白酶-9(MMP-9)、干扰素-γ(INF-γ)含量的检测对结核性脑膜炎及病毒性脑膜炎的临床诊断价值. 方法 选取解放军总医院、解放军第三0九医院自2010年8月至2011年11月住院的患者,其中结核性脑膜炎组20例,病毒性脑膜炎组15例,非感染性神经系统疾病组20例.用ELISA法检测3组患者脑脊液IL-8、MMP-9、INF-γ含量,并进行比较分析. 结果 结核性脑膜炎组患者脑脊液中IL-8、MMP-9、INF-γ的含量高于病毒性脑膜炎组和非感染性神经系统疾病组差异有统计学意义(P＜0.05).病毒性脑膜炎组患者脑脊液中IL-8、MMP-9含量高于非感染性神经系统组(P＜0.05).病毒性脑膜炎组患者脑脊液中INF-γ含量与非感染性神经系统疾病组比较差异无统计学意义(P＞0.05). 结论 脑脊液中IL-8、MMP-9、INF-γ含量的检测对结核性脑膜炎具有一定的辅助诊断意义.IL-8、MMP-9在病毒性脑膜炎的发病和进展中亦起到一定作用.临床上若在患者脑脊液中检测到高水平的INF-γ,较之IL-8、MMP-9对于结核性脑膜炎更具诊断价值.%Objective To investigate the diagnostic values of interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9) and interferon gamma (INF-γ) levels in patients with tuberculous meningitis and viral meningitis by detecting the contents of these biomarkers in the cerebrospinal fluid (CSF). Methods Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of IL-8,MMP-9 and INF-γ in the CSF of patients with tuberculous meningitis (n=20),viral meningitis (n=15) and noninfectious neurologic diseases (n=20) who admitted to our hospital from August 2010 to November 2011. Results The IL-8,MMP-9 and INF-γlevels in the samples from the tuberculous meningitis patients were significantly higher than those from either viral meningitis or noninfectious neurologic diseases (P＜0.05).The contents of IL-8

Lactobacillus rhamnosus L34 and Lactobacillus casei L39 suppress Clostridium difficile-induced IL-8 production by colonic epithelial cells

OpenAIRE

Boonma, Prapaporn; Spinler, Jennifer K; Venable, Susan F; Versalovic, James; Tumwasorn, Somying

2014-01-01

Background Clostridium difficile is the main cause of hospital-acquired diarrhea and colitis known as C. difficile-associated disease (CDAD).With increased severity and failure of treatment in CDAD, new approaches for prevention and treatment, such as the use of probiotics, are needed. Since the pathogenesis of CDAD involves an inflammatory response with a massive influx of neutrophils recruited by interleukin (IL)-8, this study aimed to investigate the probiotic effects of Lactobacillus spp....

High concentrations of pepsin in bronchoalveolar lavage fluid from children with cystic fibrosis are associated with high interleukin-8 concentrations.

LENUS (Irish Health Repository)

McNally, P

2012-02-01

BACKGROUND: Gastro-oesophageal reflux is common in children with cystic fibrosis (CF) and is thought to be associated with pulmonary aspiration of gastric contents. The measurement of pepsin in bronchoalveolar lavage (BAL) fluid has recently been suggested to be a reliable indicator of aspiration. The prevalence of pulmonary aspiration in a group of children with CF was assessed and its association with lung inflammation investigated. METHODS: This was a cross-sectional case-control study. BAL fluid was collected from individuals with CF (n=31) and healthy controls (n=7). Interleukin-8 (IL-8), pepsin, neutrophil numbers and neutrophil elastase activity levels were measured in all samples. Clinical, microbiological and lung function data were collected from medical notes. RESULTS: The pepsin concentration in BAL fluid was higher in the CF group than in controls (mean (SD) 24.4 (27.4) ng\\/ml vs 4.3 (4.0) ng\\/ml, p=0.03). Those with CF who had raised pepsin concentrations had higher levels of IL-8 in the BAL fluid than those with a concentration comparable to controls (3.7 (2.7) ng\\/ml vs 1.4 (0.9) ng\\/ml, p=0.004). Within the CF group there was a moderate positive correlation between pepsin concentration and IL-8 in BAL fluid (r=0.48, p=0.04). There was no association between BAL fluid pepsin concentrations and age, sex, body mass index z score, forced expiratory volume in 1 s or Pseudomonas aeruginosa colonisation status. CONCLUSIONS: Many children with CF have increased levels of pepsin in the BAL fluid compared with normal controls. Increased pepsin levels were associated with higher IL-8 concentrations in BAL fluid. These data suggest that aspiration of gastric contents occurs in a subset of patients with CF and is associated with more pronounced lung inflammation.

Clinical significance of measurement of serum IL-8, IL-1β and TNF-α levels after treatment in patients with periodontitis

International Nuclear Information System (INIS)

Wang Tongwu

2009-01-01

Objective: To explore the significance of changes of serum IL-8, IL-1β and TNF-α levels after treatment in patients with periodontitis. Methods: Serum IL-8, IL-1β and TNF-α(with RIA) levels were determined in 36 patients with periodontitis both before and after treatment as well as in 35 controls. Results: Before treatment, serum IL-8, IL-1β and TNF-α levels were significantly higher in the patients than those in controls (P 0.05). Conclusion: Detection of serum IL-8, IL-1β and TNF-α levels might reflect the progress of disease in patients with periodontitis and might be of important clinical value. (authors)

Interleukin 8 in progression of hormone-dependent early breast cancer

Indian Academy of Sciences (India)

The only way to perceive the real clinical course of disease and the prognostic significance of potential biomarkers is follow-up of patients who did not receive any kind of adjuvant therapy. Many studies have confirmed high levels ofinterleukin 8 (IL8) in HER2-enriched and basal-like (ER–) primary breast tumours, but less is ...

Inhibition of Toll-like receptor 2-mediated interleukin-8 production in Cystic Fibrosis airway epithelial cells via the alpha7-nicotinic acetylcholine receptor.

LENUS (Irish Health Repository)

Greene, Catherine M

2010-01-01

Cystic Fibrosis (CF) is an inherited disorder characterised by chronic inflammation of the airways. The lung manifestations of CF include colonization with Pseudomonas aeruginosa and Staphylococcus aureus leading to neutrophil-dominated airway inflammation and tissue damage. Inflammation in the CF lung is initiated by microbial components which activate the innate immune response via Toll-like receptors (TLRs), increasing airway epithelial cell production of proinflammatory mediators such as the neutrophil chemokine interleukin-8 (IL-8). Thus modulation of TLR function represents a therapeutic approach for CF. Nicotine is a naturally occurring plant alkaloid. Although it is negatively associated with cigarette smoking and cardiovascular damage, nicotine also has anti-inflammatory properties. Here we investigate the inhibitory capacity of nicotine against TLR2- and TLR4-induced IL-8 production by CFTE29o- airway epithelial cells, determine the role of alpha7-nAChR (nicotinic acetylcholine receptor) in these events, and provide data to support the potential use of safe nicotine analogues as anti-inflammatories for CF.

RESEARCH ARTICLE Interleukin 8 in progression of hormone ...

Indian Academy of Sciences (India)

24

monothioglycerol and 1,5 mM EDTA, centrifugation at 800-1000 g for 30 min, followed by .... with low IL8 levels had lower percentage of relapses and longer RFS ... diagnose women with breast cancer and to identify patients with poor ..... 20. 71. 0. 22,0. 78,0. 0. Progesterone receptor status. PRlow. PRhigh. NA. 70. 21. 0.

Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis.

Science.gov (United States)

Furlan, Larissa Lazzarini; Ribeiro, José Dirceu; Bertuzzo, Carmen Sílvia; Salomão Junior, João Batista; Souza, Dorotéia Rossi Silva; Marson, Fernando Augusto Lima

Interleukin 8 protein promotes inflammatory responses, even in airways. The presence of interleukin 8 gene variants causes altered inflammatory responses and possibly varied responses to inhaled bronchodilators. Thus, this study analyzed the interleukin 8 variants (rs4073, rs2227306, and rs2227307) and their association with the response to inhaled bronchodilators in cystic fibrosis patients. Analysis of interleukin 8 gene variants was performed by restriction fragment length polymorphism of polymerase chain reaction. The association between spirometry markers and the response to inhaled bronchodilators was evaluated by Mann-Whitney and Kruskal-Wallis tests. The analysis included all cystic fibrosis patients, and subsequently patients with two mutations in the cystic fibrosis transmembrane conductance regulator gene belonging to classes I to III. This study included 186 cystic fibrosis patients. There was no association of the rs2227307 variant with the response to inhaled bronchodilators. The rs2227306 variant was associated with FEF 50% in the dominant group and in the group with two identified mutations in the cystic fibrosis transmembrane conductance regulator gene. The rs4073 variant was associated with spirometry markers in four genetic models: co-dominant (FEF 25-75% and FEF 75% ), dominant (FEV 1 , FEF 50% , FEF 75% , and FEF 25-75% ), recessive (FEF 75% and FEF 25-75% ), and over-dominant (FEV 1 /FVC). This study highlighted the importance of the rs4073 variant of the interleukin 8 gene, regarding response to inhaled bronchodilators, and of the assessment of mutations in the cystic fibrosis transmembrane conductance regulator gene. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

IL-8 as antibody therapeutic target in inflammatory diseases: Reduction of clinical activity in palmoplantar pustulosis

DEFF Research Database (Denmark)

Skov, L.; Beurskens, F.J.; Reitamo, S.

2008-01-01

IL-8 is a chemokine that has been implicated in a number of inflammatory diseases involving neutrophil activation. HuMab 10F8 is a novel fully human mAb against IL-8, which binds a discontinuous epitope on IL-8 overlapping the receptor binding site, and which effectively neutralizes IL-8-dependent...... human neutrophil activation and migration. We investigated whether interference in the cytokine network by HuMab 10F8 might benefit patients suffering from palmoplantar pustulosis, a chronic inflammatory skin disease. Treatment of patients with HuMab 10F8 was well tolerated and significantly reduced...... clinical disease activity at all five endpoints, which included a >= 50% reduction in the formation of fresh pustules. IL-8 neutralization was monitored at the site of inflammation by assessing exudates of palmoplantar pustulosis lesions. HuMab 10F8 sequestered IL-8 in situ, as observed by rapid dose...

Characterization of Lactobacillus salivarius strains B37 and B60 capable of inhibiting IL-8 production in Helicobacter pylori-stimulated gastric epithelial cells.

Science.gov (United States)

Panpetch, Wimonrat; Spinler, Jennifer K; Versalovic, James; Tumwasorn, Somying

2016-10-18

Interleukin (IL)-8 is the key agent for initiating an inflammatory response to infection with Helicobacter pylori. Some strains of Lactobacillus spp. are known to colonize the stomach and suppress inflammation caused by H. pylori. In this study, we characterized two gastric-derived lactobacilli, Lactobacillus salivarius (LS) strains B37 and B60, capable of inhibiting H. pylori-induced IL-8 production by gastric epithelial cells. Conditioned media from LS-B37 and LS-B60 suppressed H. pylori-induced IL-8 production and mRNA expression from AGS cells without inhibiting H. pylori growth. These conditioned media suppressed the activation of NF-κB but did not suppress c-Jun activation. IL-8 inhibitory substances in conditioned media of LS-B37 and LS-B60 are heat-stable and larger than 100 kDa in size. The inhibitory activity of LS-B37 was abolished when the conditioned medium was treated with α-amylase but still remained when treated with either proteinase K, trypsin, lipase or lysozyme. The activity of LS-B60 was abolished when the conditioned medium was treated with either amylase or proteinase K but still remained when treated with lysozyme. Treatment with lipase and trypsin also significantly affected the inhibitory activity of LS-B60 although the conditioned medium retained IL-8 suppression statistically different from media control. These results suggest that L. salivarius strains B37 and B60 produce different immunomodulatory factors capable of suppressing H. pylori-induced IL-8 production from gastric epithelial cells. Our results suggest that the large, heat-stable immunomodulatory substance(s) present in the LCM of LS-B37 is a polysaccharide, while the one(s) of LS-B60 is either complex consisting of components of polysaccharide, lipid and protein or includes multiple components such as glycoprotein and lipoprotein.

Parainfluenza Virus Type 1 Induces Epithelial IL-8 Production via p38-MAPK Signalling

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Miguel Ángel Galván Morales

2014-01-01

Full Text Available Human parainfluenza virus type 1 (HPIV-1 is the most common cause of croup in infants. The aim of this study was to describe molecular mechanisms associated with IL-8 production during HPIV-1 infection and the role of viral replication in MAPK synthesis and activation. An in vitro model of HPIV-1 infection in the HEp-2 and A549 cell lines was used; a kinetic-based ELISA for IL-8 detection was also used, phosphorylation of the mitogen-activated protein kinases (MAPKs was identified by Western blot analysis, and specific inhibitors for each kinase were used to identify which MAPK was involved. Inactivated viruses were used to assess whether viral replication is required for IL-8 production. Results revealed a gradual increase in IL-8 production at different selected times, when phosphorylation of MAPK was detected. The secretion of IL-8 in the two cell lines infected with the HPIV-1 is related to the phosphorylation of the MAPK as well as viral replication. Inhibition of p38 suppressed the secretion of IL-8 in the HEp-2 cells. No kinase activation was observed when viruses were inactivated.

The effect of interleukin-8 and granulocyte macrophage colony stimulating factor on the response of neutrophils to formyl methionyl leucyl phenylalanine.

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Mikami, M; Llewellyn-Jones, C G; Stockley, R A

1998-08-14

Neutrophils isolated from patients with chronic bronchitis and emphysema have been shown to have enhanced responses to formyl peptides when assessed in vitro compared to age, sex matched controls. It is currently unclear whether the observed differences are due to a 'priming' effect by a second agent in vivo, or whether this is a primary difference in the neutrophils. We have studied the effects of interleukin-8, which is thought to be one of the major pro-inflammatory cytokines in chronic lung disease and granulocyte macrophage colony stimulating factor (GMCSF), in order to assess their effects on neutrophil chemotaxis and connective tissue degradation. In addition, we have assessed the effect of preincubation of these agents with neutrophils for 30 min followed by stimulation with F-Met-Leu-Phe (FMLP) to investigate any possible 'priming' effect that may be relevant to our clinical data. We report suppression of neutrophil chemotaxis to FMLP following incubation of the neutrophils with both IL-8 and GMCSF. However, we have observed an additive effect of IL-8 and FMLP for neutrophil degranulation leading to fibronectin degradation. The results suggest that IL-8 does not 'prime' neutrophils for subsequent FMLP stimulation as observed in vivo. Although the results for GMCSF were similar for the chemotactic response, the agent also had a synergistic effect on connective tissue degradation. However, it is concluded that neither agent could explain the enhanced neutrophil responses seen in our patients.

ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion.

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Chen, Wei-Ta; Ebelt, Nancy D; Stracker, Travis H; Xhemalce, Blerta; Van Den Berg, Carla L; Miller, Kyle M

2015-06-01

Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse xenograft model and clinical data validated IL-8 in lung metastasis. These findings provide insights into how ATM activation by oxidative stress regulates IL-8 to sustain cell migration and invasion in cancer cells to promote metastatic potential. Thus, in addition to well-established roles in tumor suppression, these findings identify a role for ATM in tumor progression.

Relationship of serum levels of interleukin 6, interleukin 8, and C-reactive protein with forced expiratory volume in first second in patients with mustard lung and chronic obstructive pulmonary diseases: systematic review and meta-analysis.

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Shahriary, Alireza; Panahi, Yunes; Shirali, Saeed; Rahmani, Hossein

2017-06-01

The chronic systemic inflammation is a result of releasing inflammatory cytokines from the cells relating to the body immunity system and chronic activation of the innate immunity system. To evaluate the relationship among serum levels of interleukin 6 (IL-6), interleukin 8 (IL-8), C-reactive protein (CRP) with forced expiratory volume in 1 st s (FEV 1 ) in patients with mustard lung (ML) and chronic obstructive pulmonary diseases (COPD). A published literature search was performed through SID, web of science, ISI, Science Direct, Scopus, Medline, and PubMed databases for articles published in English. The correlation coefficient ( r ) and 95% confidence intervals (95% CIs) were calculated using random or fixed effects models. Heterogeneity was assessed using χ 2 and I 2 statistics. In total, 4 published studies were included in the final analysis. Using the random-effect model, meta-analysis showed that the r was -0.052 (95% CI: -0.14-0.049, p = 0.28) at serum level of IL-8, serum levels of CRP and FEV 1 in these results were r = -0.13, p = 0.012, serum levels of tumor necrosis factor (TNF) and FEV 1 levels were r = -0.39, p = 0.03 in the conducted studies on mustard lung patients. The IL-6 serum level was explored in COPD patients. The results of the given studies in these patients are r = -0.006, 95% CI: -0.37-0.15, and p = 0.44. In this meta-analysis, there was evidence that serum levels of CRP and TNF have been significantly increased in chronic obstructive pulmonary diseases compared to the healthy control group, which signifies the presence of systemic inflammation in ML and COPD patients.

Increased expression of TLR9 associated with pro-inflammatory S100A8 and IL-8 in diabetic wounds could lead to unresolved inflammation in type 2 diabetes mellitus (T2DM) cases with impaired wound healing.

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Singh, Kanhaiya; Agrawal, Neeraj K; Gupta, Sanjeev K; Sinha, Pratima; Singh, Kiran

2016-01-01

Type 2 diabetes mellitus (T2DM) is characterized by persistent hyperglycemia which causes a chain of abrupt biochemical and physiological changes. Immune dys-regulation is the hallmark of T2DM that could contribute to prolonged inflammation causing transformation of wounds into non-healing chronic ulcers. Toll like receptor -9 (TLR9) is a major receptor involved in innate immune regulation. TLR9 activation induces release of pro-inflammatory molecules like S100A8 and interleukin-8 (IL-8) by myeloid cells causing migration of myeloid cells to the site of inflammation. We hypothesized that pro-inflammatory S100A8 and IL-8 proteins could cause persistent inflammation in chronic wounds like diabetic foot ulcer (DFU) and may contribute to impaired wound healing in T2DM patients. Expression of TLR9 and its downstream effector molecules S100A8, and IL-8 were analyzed in chronic diabetic wound and non-diabetic control wound tissue samples by semiquantitative reverse transcriptase - polymerase chain reaction (RT-PCR), quantitative RT-PCR, western blot and immunofluorescence. CD11b(+)CD33(+) myeloid cells were analyzed by flow cytometry. TLR9 message and protein were higher in diabetic wounds compared to control wounds (p=0.03, t=2.21 for TLR9 mRNA; p=diabetic wounds (p=0.003, t=3.1 for S100A8 mRNA; p=0.04, t=2.04 for IL-8). CD11b(+) CD33(+) myeloid cells were decreased in T2DM as compared to non-diabetic controls (p=0.001, t=3.6). DFU subjects had higher levels of CD11b(+) CD33(+) myeloid cells as compared to non-DFU T2DM control (p=0.003, t=2.8). Infection in the wound microenvironment could be the cause of increase in CD11b(+)CD33(+) myeloid cells in DFU (p=0.03, t=2.5). The up-regulation of myeloid cell-derived pro-inflammatory molecules S100A8 and IL-8 in combination with lower levels of CD11b(+) CD33(+) myeloid cells may cause the impairment of wound healing in T2DM subjects leading to chronic ulcers. Copyright © 2016 Elsevier Inc. All rights reserved.

A reversion of an IL2RG mutation in combined immunodeficiency providing competitive advantage to the majority of CD8+ T cells.

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Kuijpers, Taco W; van Leeuwen, Ester M M; Barendregt, Barbara H; Klarenbeek, Paul; aan de Kerk, Daan J; Baars, Paul A; Jansen, Machiel H; de Vries, Niek; van Lier, René A W; van der Burg, Mirjam

2013-07-01

Mutations in the common gamma chain (γc, CD132, encoded by the IL2RG gene) can lead to B(+)T(-)NK(-) X-linked severe combined immunodeficiency, as a consequence of unresponsiveness to γc-cytokines such as interleukins-2, -7 and -15. Hypomorphic mutations in CD132 may cause combined immunodeficiencies with a variety of clinical presentations. We analyzed peripheral blood mononuclear cells of a 6-year-old boy with normal lymphocyte counts, who suffered from recurrent pneumonia and disseminated mollusca contagiosa. Since proliferative responses of T cells and NK cells to γc -cytokines were severely impaired, we performed IL2RG gene analysis, showing a heterozygous mutation in the presence of a single X-chromosome. Interestingly, an IL2RG reversion to normal predominated in both naïve and antigen-primed CD8(+) T cells and increased over time. Only the revertant CD8(+) T cells showed normal expression of CD132 and the various CD8(+) T cell populations had a different T-cell receptor repertoire. Finally, a fraction of γδ(+) T cells and differentiated CD4(+)CD27(-) effector-memory T cells carried the reversion, whereas NK or B cells were repeatedly negative. In conclusion, in a patient with a novel IL2RG mutation, gene-reverted CD8(+) T cells accumulated over time. Our data indicate that selective outgrowth of particular T-cell subsets may occur following reversion at the level of committed T progenitor cells.

Decreased number of CD4+ and CD8+ T cells that express the interleukin-7 receptor in blood and tissues of SIV-infected macaques

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Moniuszko, Marcin; Edghill-Smith, Yvette; Venzon, David; Stevceva, Liljana; Nacsa, Janos; Tryniszewska, Elzbieta; Tsai, Wen-Po; Franchini, Genoveffa

2006-01-01

Acute HIV/SIV (human/simian immunodeficiency virus) infection results in severe CD4 + T cell depletion in lymphoid compartments. During the chronic phase of infection, CD4 + T cell numbers rebound in blood but remain low in the gut-associated lymphoid tissue (GALT), even when viral replication is suppressed by antiretroviral therapy (ART). Thus, strategies to repopulate lymphoid compartments may ameliorate the clinical outcome of HIV/SIV infection. Interleukin (IL)-7 is a key cytokine for the maintenance of homeostatic proliferation of T cells. In HIV/SIV infection, IL-7 expression is increased, likely to compensate for T cell loss, suggesting that supraphysiological administration of IL-7 could provide additional benefit. However, the ability of T cells to respond to IL-7 is dependent on the level of expression of the IL-7 receptor (IL-7R) in T cells in various body compartments. In here, we investigated the proportion of IL-7R + T cells in blood, spleen, gut, and genitourinary tract of healthy and SIV-infected macaques with various degrees of CD4 + T cell depletion. We found that the percentage of T cells expressing IL-7R was significantly lower in both CD4 + and CD8 + T cell subsets in SIV-infected macaques than in healthy animals and this decrease directly correlated with the CD4 + T cell number. Importantly, the proportion of CD4 + and CD8 + T cells expressing IL-7R in blood paralleled that found in tissues. IL-7R + T cells within the SIV-specific CD8 + T cells varied and were lowest in most tissues of viremic macaques, likely reflecting continuous antigen stimulation of effector cells

S100A8/A9 (Calprotectin), Interleukin-6, and C-Reactive Protein in Obesity and Diabetes before and after Roux-en-Y Gastric Bypass Surgery

DEFF Research Database (Denmark)

Lylloff, Louise; Bathum, Lise; Madsbad, Sten

2017-01-01

Background: In obesity, which is a major contributor to insulin resistance and diabetes, the circulating level of S100A8/A9 (calprotectin) is elevated and declines after Roux-en-Y gastric bypass surgery (RYGB). However, studies on S100A8/A9 and the pathophysiological mechanisms in insulin...... resistance and diabetes are few and contradictory. Methods: We studied 48 subjects who underwent RYGB, comprising a non-diabetic control group and two diabetic groups in whom diabetes either regressed or persisted, 6-12 months post-surgically. S100A8/A9, interleukin 6 (IL-6) as well as other inflammatory...... and diabetes-related markers were measured pre- A nd post-surgically. Results: Significant and similar decreases of BMI were found in all groups. S100A8/A9 and IL-6 decreased significantly in the group with diabetes remission and in the control group, but not in the group with persistent diabetes. The relative...

Clinical significance of determination of changes of serum GM-CSF, IL-8, IL-6 levels after treatment in pediatric patients with bronchial asthma

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Xue Hongfeng

2006-01-01

Objective: To investigate the changes of serum GM-CSF, IL-8 and IL-6 levels both before and after treatment in pediatric patients with bronchial asthma. Methods: Serum GM-CSF, IL-8 and IL-6 levels were measured with RIA in 32 pediatric patients with bronchial asthma both before and after treatment as well as in 30 controls. Results: Before treatment, the serum GM-CSF, IL-8, IL-6 levels were significantly higher in the patients than those in the controls (P 0.05). Conclusion: Abnormal high serum GM-CSF, IL-8, IL-6 levels played important role in the pathogenesis of bronchial asthma in children. (authors)

Insulin Like Growth Factor-1 (IGF-1 Causes Overproduction of IL-8, an Angiogenic Cytokine and Stimulates Neovascularization in Isoproterenol-Induced Myocardial Infarction in Rats

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Nagaraja Haleagrahara

2011-11-01

Full Text Available Angiogenesis factors are produced in response to hypoxic or ischemic insult at the site of pathology, which will cause neovascularization. Insulin like growth factor-1 (IGF-1 exerts potent proliferative, angiogenic and anti-apoptotic effects in target tissues. The present study was aimed to evaluate the effects of IGF-1 on circulating level of angiogenic cytokine interleukin-8 (IL-8, in experimentally-induced myocardial ischemia in rats. Male Sprague-Dawley rats were divided into control, IGF-1 treated (2 µg/kg/day subcutaneously, for 5 and 10 days, isoproterenol (ISO treated (85 mg/kg, subcutaneously for two days and ISO with IGF-1 treated (for 5 and 10 days. Heart weight, serum IGF-1, IL-8 and cardiac marker enzymes (CK-MB and LDH were recorded after 5 and 10 days of treatment. Histopathological analyses of the myocardium were also done. There was a significant increase in serum cardiac markers with ISO treatment indicating myocardial infarction in rats. IGF-1 level increased significantly in ISO treated groups and the level of IGF-1 was significantly higher after 10 days of treatment. IL-8 level increased significantly after ISO treatment after 5 and 10 days and IGF-1 concurrent treatment to ISO rats had significantly increased IL-8 levels. Histopathologically, myocyte necrosis and nuclear pyknosis were reduced significantly in IGF-1 treated group and there were numerous areas of capillary sprouting suggestive of neovascularization in the myocardium. Thus, IGF-1 protects the ischemic myocardium with increased production of circulating angiogenic cytokine, IL-8 and increased angiogenesis.

IL-23 (Interleukin-23)-Producing Conventional Dendritic Cells Control the Detrimental IL-17 (Interleukin-17) Response in Stroke.

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Gelderblom, Mathias; Gallizioli, Mattia; Ludewig, Peter; Thom, Vivien; Arunachalam, Priyadharshini; Rissiek, Björn; Bernreuther, Christian; Glatzel, Markus; Korn, Thomas; Arumugam, Thiruma Valavan; Sedlacik, Jan; Gerloff, Christian; Tolosa, Eva; Planas, Anna M; Magnus, Tim

2018-01-01

Inflammatory mechanisms can exacerbate ischemic tissue damage and worsen clinical outcome in patients with stroke. Both αβ and γδ T cells are established mediators of tissue damage in stroke, and the role of dendritic cells (DCs) in inducing the early events of T cell activation and differentiation in stroke is not well understood. In a murine model of experimental stroke, we defined the immune phenotype of infiltrating DC subsets based on flow cytometry of surface markers, the expression of ontogenetic markers, and cytokine levels. We used conditional DC depletion, bone marrow chimeric mice, and IL-23 (interleukin-23) receptor-deficient mice to further explore the functional role of DCs. We show that the ischemic brain was rapidly infiltrated by IRF4 + /CD172a + conventional type 2 DCs and that conventional type 2 DCs were the most abundant subset in comparison with all other DC subsets. Twenty-four hours after ischemia onset, conventional type 2 DCs became the major source of IL-23, promoting neutrophil infiltration by induction of IL-17 (interleukin-17) in γδ T cells. Functionally, the depletion of CD11c + cells or the genetic disruption of the IL-23 signaling abrogated both IL-17 production in γδ T cells and neutrophil infiltration. Interruption of the IL-23/IL-17 cascade decreased infarct size and improved neurological outcome after stroke. Our results suggest a central role for interferon regulatory factor 4-positive IL-23-producing conventional DCs in the IL-17-dependent secondary tissue damage in stroke. © 2017 American Heart Association, Inc.

Osteoblasts derived from osteophytes produce interleukin-6, interleukin-8, and matrix metalloproteinase-13 in osteoarthritis.

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Sakao, Kei; Takahashi, Kenji A; Arai, Yuji; Saito, Masazumi; Honjo, Kuniaki; Hiraoka, Nobuyuki; Asada, Hidetsugu; Shin-Ya, Masaharu; Imanishi, Jiro; Mazda, Osam; Kubo, Toshikazu

2009-01-01

To clarify the significance of the osteophytes that appear during the progression of osteoarthritis (OA), we investigated the expression of inflammatory cytokines and proteases in osteoblasts from osteophytes. We also examined the influence of mechanical stress loading on osteoblasts on the expression of inflammatory cytokines and proteases. Osteoblasts were isolated from osteophytes in 19 patients diagnosed with knee OA and from subchondral bone in 4 patients diagnosed with femoral neck fracture. Messenger RNA expression and protein production of inflammatory cytokines and proteases were analyzed using real-time RT-PCR and ELISA, respectively. To examine the effects of mechanical loading, continuous hydrostatic pressure was applied to the osteoblasts. We determined the mRNA expression and protein production of IL-6, IL-8, and MMP-13, which are involved in the progression of OA, were increased in the osteophytes. Additionally, when OA pathological conditions were simulated by applying a nonphysiological mechanical stress load, the gene expression of IL-6 and IL-8 increased. Our results suggested that nonphysiological mechanical stress may induce the expression of biological factors in the osteophytes and is involved in OA progression. By controlling the expression of these genes in the osteophytes, the progression of cartilage degeneration in OA may be reduced, suggesting a new treatment strategy for OA.

Clinical significance of determination of changes of serum IGF-II, IL-6, IL-8, TNF-α levels after treatment in children with bronchopneumonia

International Nuclear Information System (INIS)

Feng Yue

2011-01-01

Objective: To explore the clinical significance of changes of serum IGF-II, IL-6, IL-8 and TNF-α levels after treatment in children with bronchopneumonia. Methods: Serum IGF-II, IL-6, IL-8 and TNF-α levels with RIA were detected both before and after treatment in 33 patients with children bronchopneumonia as well as in 35 controls. Results: Before treatment, serum IGF-II, IL-6, IL-8 and TNF-α levels were significantly higher in the patients than those in the controls (P 0.05). Conclusions: Serum IGF-II, IL-6, IL-8 and TNF-α could take part in the pathogenesis of children bronchopneumonia in various ways and determination of these levels was clinically important. (authors)

Clinical significance of measurement of changes of serum hs-CRP, IL-6, IL-8 M-CSF levels after treatment in patients with endometriosis

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Chen Xiaochao; Zhou Dongxia; Zhang Limin; Liu Hongshu

2008-01-01

Objective: To explore the significance of changes of serum hs-CRP, IL-6, IL-8 and M-CSF levels after treatment in patients with endometriosis. Methods: Serum IL-6, IL-8, M -CSF(with RIA), hs-CRP(with immuneturbidity method)levels were determined in 33 patients with endometriosis both before and after treatment as well as in 35 controls. Results: Before treatment, the serum hs-CRP, IL-6, IL-8 and M-CSF levels were significantly higher in the patients than those in controls (P 0.05). Conclusion: Detection of serum hs-CRP, IL-6, IL-8 and M-CSF levels might reflect the progress of diseases in patients with endometriosis. (authors)

Differential Effects of Statins on Inflammatory Interleukin-8 and Antimicrobial Peptide Human Β-Defensin 2 Responses in Salmonella-Infected Intestinal Epithelial Cells

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Fu-Chen Huang

2018-06-01

Full Text Available Alternative therapies are needed to reduce the use of antibiotics and incidence of drug-resistant Salmonellosis. Previous studies have revealed important roles of statins in regulating innate immunity. Therefore, we investigated the effects of statins on innate immunity in Salmonella-infected intestinal epithelial cells (IECs, which are involved in mucosal innate immunity. SW480 cells and Akt siRNA- or vitamin D receptor (VDR siRNA-transfected SW480 cells were infected by wild-type S. Typhimurium strain SL1344 in the presence or absence of statins. The mRNA or protein expression was analyzed by real-time quantitative PCR or western blot analysis, respectively. Simvastatin or fluvastatin caused IL-8 (interleukin-8 suppression, but increased hBD-2 mRNA expression in Salmonella-infected SW480 cells. Both statins enhanced phosphorylated Akt and VDR expressions. Akt or VDR knockdown by siRNA counteracted the suppressive effect of simvastatin on IL-8 expression, whereas VDR knockdown diminished the enhanced hBD-2 expression in Salmonella-infected SW480 cells. Therefore, we observed differential regulation of statins on inflammatory IL-8 and anti-microbial hBD-2 expressions in Salmonella-infected IECs via PI3K/Akt signaling and VDR protein expression, respectively. The enhanced activity of antimicrobial peptides by statins in Salmonella-infected IECs could protect the host against infection, and modulation of pro-inflammatory responses could prevent the detrimental effects of overwhelming inflammation in the host.

Effect of ultrasound on the interleukin content in blood of rats with experimental inflammation

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Nurishchenko, N.Je.

2015-01-01

The aim was to determine the effectiveness of anti-inflammatory action of ultrasound by the interleukin-6, interleukin-8 and tumor necrosis factor alpha content in the blood of rats with experimental inflammation. The study was performed using conventional models of inflammation - carrageenan- induced edema of the limbs of rats. Content interleukins Il-6 and Il-8 were determined by enzyme immunoassay (ELISA) according to a standard protocol Immunoassay kit, Biosourse (USA). The content of TNF-α was determined by cytotoxic effect on sensitive mouse fibroblast line L- 929. It was shown that in the group of rats with carrageenan-induced edema contents of IL-6 increase in 2.8 times, IL-8 - in 5.6 times, and TNF-α- in 3 times compared to the control. Course influence of ultra sound contributed to reduction of the studied parameters. The content of IL-6 decreased in 1.7 times, IL-8 and TNF-α- in 1.6 times in comparison with inflammation

Lactobacillus rhamnosus L34 and Lactobacillus casei L39 suppress Clostridium difficile-induced IL-8 production by colonic epithelial cells

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2014-01-01

Background Clostridium difficile is the main cause of hospital-acquired diarrhea and colitis known as C. difficile-associated disease (CDAD).With increased severity and failure of treatment in CDAD, new approaches for prevention and treatment, such as the use of probiotics, are needed. Since the pathogenesis of CDAD involves an inflammatory response with a massive influx of neutrophils recruited by interleukin (IL)-8, this study aimed to investigate the probiotic effects of Lactobacillus spp. on the suppression of IL-8 production in response to C. difficile infection. Results We screened Lactobacillus conditioned media from 34 infant fecal isolates for the ability to suppress C. difficile-induced IL-8 production from HT-29 cells. Factors produced by two vancomycin-resistant lactobacilli, L. rhamnosus L34 (LR-L34) and L.casei L39 (LC-L39), suppressed the secretion and transcription of IL-8 without inhibiting C. difficile viability or toxin production. Conditioned media from LR-L34 suppressed the activation of phospho-NF-κB with no effect on phospho-c-Jun. However, LC-L39 conditioned media suppressed the activation of both phospho-NF-κB and phospho-c-Jun. Conditioned media from LR-L34 and LC-L39 also decreased the production of C. difficile-induced GM-CSF in HT-29 cells. Immunomodulatory factors present in the conditioned media of both LR-L34 and LC-L39 are heat-stable up to 100°C and > 100 kDa in size. Conclusions Our results suggest that L. rhamnosus L34 and L. casei L39 each produce factors capable of modulating inflammation stimulated by C. difficile. These vancomycin-resistant Lactobacillus strains are potential probiotics for treating or preventing CDAD. PMID:24989059

Lactobacillus rhamnosus L34 and Lactobacillus casei L39 suppress Clostridium difficile-induced IL-8 production by colonic epithelial cells.

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Boonma, Prapaporn; Spinler, Jennifer K; Venable, Susan F; Versalovic, James; Tumwasorn, Somying

2014-07-02

Clostridium difficile is the main cause of hospital-acquired diarrhea and colitis known as C. difficile-associated disease (CDAD).With increased severity and failure of treatment in CDAD, new approaches for prevention and treatment, such as the use of probiotics, are needed. Since the pathogenesis of CDAD involves an inflammatory response with a massive influx of neutrophils recruited by interleukin (IL)-8, this study aimed to investigate the probiotic effects of Lactobacillus spp. on the suppression of IL-8 production in response to C. difficile infection. We screened Lactobacillus conditioned media from 34 infant fecal isolates for the ability to suppress C. difficile-induced IL-8 production from HT-29 cells. Factors produced by two vancomycin-resistant lactobacilli, L. rhamnosus L34 (LR-L34) and L.casei L39 (LC-L39), suppressed the secretion and transcription of IL-8 without inhibiting C. difficile viability or toxin production. Conditioned media from LR-L34 suppressed the activation of phospho-NF-κB with no effect on phospho-c-Jun. However, LC-L39 conditioned media suppressed the activation of both phospho-NF-κB and phospho-c-Jun. Conditioned media from LR-L34 and LC-L39 also decreased the production of C. difficile-induced GM-CSF in HT-29 cells. Immunomodulatory factors present in the conditioned media of both LR-L34 and LC-L39 are heat-stable up to 100°C and > 100 kDa in size. Our results suggest that L. rhamnosus L34 and L. casei L39 each produce factors capable of modulating inflammation stimulated by C. difficile. These vancomycin-resistant Lactobacillus strains are potential probiotics for treating or preventing CDAD.

Clinical significance of determination of changes of serum IL-8, IL-1β and TNF-α levels after treatment in patients with chronic prostatitis

International Nuclear Information System (INIS)

Lv Yuhong; Zhang Zaigao; Li Jiacheng

2009-01-01

Objective: To study the significance of changes of serum IL-8, IL-1β and TNF-α levels after treatment in patients with chronic prostatitis. Methods: Serum TNF-α (with RIA). IL-8, IL-1β(with ELISA) levels were determined in 40 patients with chronic prostatitis both before and after treatment as well as 35 controls. Results: Before treatment, the serum IL-8, IL-1β and TNF-α levels in the patients were significantly higher than those in controls (P<0.01). After 2 weeks treatment, the IL-8 and IL-1β levels dropped markedly, but remained significantly higher than those in controls (P<0.05). However,the serum TNF-α levels dropped more and were not much different from those in controls (P<0.05). Conclusion: IL-8, IL-1β and TNF-α could take part in the pathogenesis in chronic prostatitis in various ways and determination of these levels clinically important. (authors)

Ikaros imposes a barrier to CD8+ T cell differentiation by restricting autocrine IL-2 production.

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O'Brien, Shaun; Thomas, Rajan M; Wertheim, Gerald B; Zhang, Fuqin; Shen, Hao; Wells, Andrew D

2014-06-01

Naive CD4(+) T cells require signals from the TCR and CD28 to produce IL-2, expand, and differentiate. However, these same signals are not sufficient to induce autocrine IL-2 production by naive CD8(+) T cells, which require cytokines provided by other cell types to drive their differentiation. The basis for failed autocrine IL-2 production by activated CD8(+) cells is unclear. We find that Ikaros, a transcriptional repressor that silences IL-2 in anergic CD4(+) T cells, also restricts autocrine IL-2 production by CD8(+) T cells. We find that CD8(+) T cell activation in vitro in the absence of exogenous cytokines and CD4 help leads to marked induction of Ikaros, a known repressor of the Il2 gene. Naive murine CD8 T cells haplo-insufficient for Ikzf1 failed to upregulate Ikaros, produced autocrine IL-2, and differentiated in an IL-2-dependent manner into IFN-γ-producing CTLs in response to TCR/CD28 stimulation alone. Furthermore, Ikzf1 haplo-insufficient CD8(+) T cells were more effective at controlling Listeria infection and B16 melanoma growth in vivo, and they could provide help to neighboring, non-IL-2-producing cells to differentiate into IFN-γ-producing effectors. Therefore, by repressing autocrine IL-2 production, Ikaros ensures that naive CD8(+) T cells remain dependent on licensing by APCs and CD4(+) T cells, and it may therefore act as a cell-intrinsic safeguard against inappropriate CTL differentiation and immunopathology. Copyright © 2014 by The American Association of Immunologists, Inc.

Catechol Groups Enable Reactive Oxygen Species Scavenging-Mediated Suppression of PKD-NFkappaB-IL-8 Signaling Pathway by Chlorogenic and Caffeic Acids in Human Intestinal Cells

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Hee Soon Shin

2017-02-01

Full Text Available Chlorogenic acid (CHA and caffeic acid (CA are phenolic compounds found in coffee, which inhibit oxidative stress-induced interleukin (IL-8 production in intestinal epithelial cells, thereby suppressing serious cellular injury and inflammatory intestinal diseases. Therefore, we investigated the anti-inflammatory mechanism of CHA and CA, both of which inhibited hydrogen peroxide (H2O2-induced IL-8 transcriptional activity. They also significantly suppressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB transcriptional activity, nuclear translocation of the p65 subunit, and phosphorylation of IκB kinase (IKK. Additionally, upstream of IKK, protein kinase D (PKD was also suppressed. Finally, we found that they scavenged H2O2-induced reactive oxygen species (ROS and the functional moiety responsible for the anti-inflammatory effects of CHA and CA was the catechol group. Therefore, we conclude that the presence of catechol groups in CHA and CA allows scavenging of intracellular ROS, thereby inhibiting H2O2-induced IL-8 production via suppression of PKD-NF-κB signaling in human intestinal epithelial cells.

Effects of different types of anaesthesia (regional vs general) on serum IL-6, IL-8 and M-CSF levels in surgical patients

International Nuclear Information System (INIS)

Xiao Jiawang

2009-01-01

Objective: To study the effect of anesthesia(regional vs general) on serum IL-6, IL-8 and M-CSF levels in surgical patients. Methods: Serum IL-6, IL-8 and M-CSF levels were determined with RIA 3 times in 34 patients operated under ragional anesthesia and 34 patients operted under general anesthesia (both for benign gastral ulcer). The levels were measured before induction of anesthesia, at beginning of operation and 1 hr later. Results: In patients under regional anesthesia, the IL-6, IL-8 and M-CSF levels increased significantly at the beginning of operation and 1 hr later. Though dropped remained significantly higher than the levels before induction (P<0.05); No significant change of the levels were obsorved in patients under general anesthesia through the operation, and the levels were as a whole significantly lower than the levels under regional anesthesia (P<0.05). Conclusion: General anesthesia (combined intravenous and inhalation) could abolish increases of serum IL-6, IL-8 and M-CSF levels during operation must be of clinical values. (authors)

Possible role for interleukins as biomarkers for mortality and recurrence in oral cancer.

Science.gov (United States)

Arduino, Paolo G; Menegatti, Elisa; Cappello, Nazario; Martina, Eugenio; Gardino, Nicolò; Tanteri, Carlotta; Cavallo, Franco; Scully, Crispian; Broccoletti, Roberto

2015-05-26

Salivary and serum levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) have previously been studied in oral cancer with conflicting results. We designed a controlled study to assess the correlation between pretreatment salivary and serum levels of IL-6 and IL-8, and all-cause survival and cancer recurrence in oral cancer patients. Fifty-two oral cancer patients and 52 healthy control cases were selected. In univariate analysis, salivary IL-6 and IL-8 seemed to be more expressed in cases (p<0.001 and p = 0.010, respectively). Multivariate analysis showed that higher pretreatment saliva IL-6 levels were significantly associated with better survival (hazard ratio [HR] = 8.62; 95% confidence interval [95% CI], 1.21-62.50; p = 0.031). To date, this is the largest prospective controlled study that has analyzed the pretreatment salivary and serum levels of IL-6 and IL-8 in oral cancer patients, suggesting salivary IL-6 as a possible prognostic biomarker. But further validation in a larger sample is still necessary.

Elucidation of Distinct Roles of Guinea Pig CXCR1 and CXCR2 in Neutrophil Migration toward IL-8 and GROα by Specific Antibodies.

Science.gov (United States)

Tanaka, Kento; Yoshitomi, Tomomi; Hirahara, Kazuki

2017-01-01

Chemokine receptors CXCR1 and CXCR2 are conserved between guinea pigs and humans, but the distinct role of each receptor in chemotactic responses of neutrophils against chemokine ligands has not been elucidated due in part to the lack of specific inhibitors against these receptors in guinea pigs. In this study, we investigated the roles of guinea pig CXCR1 and CXCR2 on neutrophils in chemotactic responses to guinea pig interleukin (IL)-8 and growth-regulated oncogene (GRO)α by using specific inhibitory antibodies against these receptors. Neutrophil migration induced by IL-8 was partially inhibited by either anti-CXCR1 antibody or anti-CXCR2 antibody. In addition, the migration was inhibited completely when both anti-CXCR1 and anti-CXCR2 antibodies were combined. On the other hand, neutrophil migration induced by GROα was not inhibited by anti-CXCR1 antibody while inhibited profoundly by anti-CXCR2 antibody. These results indicated that CXCR1 and CXCR2 mediated migration induced by the IL-8 synergistically and only CXCR2 mediated migration induced by GROα in guinea pig neutrophils. Our findings on ligand selectivity of CXCR1 and CXCR2 in guinea pigs are consistent with those in humans.

Interleukin 1 β (IL-1B) and IL-1 antagonist receptor (IL-1RN) gene polymorphisms are associated with the genetic susceptibility and steroid dependence in patients with ulcerative colitis.

Science.gov (United States)

Yamamoto-Furusho, Jesús K; Santiago-Hernández, Jean J; Pérez-Hernández, Nonanzit; Ramírez-Fuentes, Silvestre; Fragoso, José Manuel; Vargas-Alarcón, Gilberto

2011-07-01

Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. Among cytokines induced in UC, interleukin 1 antagonist (IL-1ra) and interleukin 1 β (IL-1β) seems to have a central role because of its immunoregulatory and proinflammatory activities. To determine the association between IL-1RA and IL-1B gene polymorphisms and the clinical features of UC in the Mexican Mestizo population. Five polymorphisms in the IL-1 gene cluster members IL-1B (rs16944), IL1F10 (rs3811058), and IL-1RN (rs419598, rs315952, and rs315951) were genotyped by 5' exonuclease TaqMan genotyping assays in a group of 200 Mexican patients with UC and 248 ethnically matched unrelated healthy controls. We found a significant increased frequencies of IL-1RN6/1 TC (rs315952) and RN6/2 CC (rs315951) and decreased frequency of IL-1B-511 TC (rs16944) genotypes in UC patients as compared with healthy controls. In the subgroup analysis, we found a significant association between the RN6/2 GG (rs315951) and IL-1B-511 CC (rs16944) genotypes and the presence of steroid-dependence in UC patients (pC=00001, OR=15.6 and pC=0.008, OR=4.09, respectively). Patients with UC showed increased frequencies of IL-1RN "CTC" and "TCG" haplotypes when compared with healthy controls (P=0.019, OR=1.43 and P<10(-7), OR=2.63, respectively). Two haplotypes (TTG and CTG) showed decreased frequency in patients when compared with healthy controls (P=9×10(-7), OR=0.11 and P=8×10(-6), OR=0.11, respectively). IL-1 RN and IL-1B polymorphisms were associated with the genetic susceptibility to develop UC and might be associated with the presence of steroid-dependence in UC patients.

Mycobacterium abscessus glycopeptidolipid prevents respiratory epithelial TLR2 signaling as measured by HβD2 gene expression and IL-8 release.

Directory of Open Access Journals (Sweden)

Lisa B Davidson

Full Text Available Mycobacterium abscessus has emerged as an important cause of lung infection, particularly in patients with bronchiectasis. Innate immune responses must be highly effective at preventing infection with M. abscessus because it is a ubiquitous environmental saprophyte and normal hosts are not commonly infected. M. abscessus exists as either a glycopeptidolipid (GPL expressing variant (smooth phenotype in which GPL masks underlying bioactive cell wall lipids, or as a variant lacking GPL which is immunostimulatory and invasive in macrophage infection models. Respiratory epithelium has been increasingly recognized as playing an important role in the innate immune response to pulmonary pathogens. Respiratory epithelial cells express toll-like receptors (TLRs which mediate the innate immune response to pulmonary pathogens. Both interleukin-8 (IL-8 and human β-defensin 2 (HβD2 are expressed by respiratory epithelial cells in response to toll-like receptor 2 (TLR2 receptor stimulation. In this study, we demonstrate that respiratory epithelial cells respond to M. abscessus variants lacking GPL with expression of IL-8 and HβD2. Furthermore, we demonstrate that this interaction is mediated through TLR2. Conversely, M. abscessus expressing GPL does not stimulate expression of IL-8 or HβD2 by respiratory epithelial cells which is consistent with "masking" of underlying bioactive cell wall lipids by GPL. Because GPL-expressing smooth variants are the predominant phenotype existing in the environment, this provides an explanation whereby initial M. abscessus colonization of abnormal lung airways escapes detection by the innate immune system.

Thymosin beta-4 promotes mesenchymal stem cell proliferation via an interleukin-8-dependent mechanism

International Nuclear Information System (INIS)

Jeon, Byung-Joon; Yang, Yoolhee; Kyung Shim, Su; Yang, Heung-Mo; Cho, Daeho; Ik Bang, Sa

2013-01-01

Mesenchymal stem cells (MSCs) hold great promise for the field of tissue regeneration. Because only a limited number of MSCs can be obtained from each donor site, it is important to establish standard methods for MSC expansion using growth and trophic factors. Thymosin β4 (Tβ4) is a novel trophic factor that has antimicrobial effects and the potential to promote tissue repair. Tβ4 is a ubiquitous, naturally-occurring peptide in the wound bed. Therefore, the relationship between Tβ4 and MSCs, especially adjacent adipose tissue-derived stem cells (ASCs), merits consideration. Exogenous Tβ4 treatment enhanced the proliferation of human ASCs, resulting in prominent nuclear localization of PCNA immunoreactivity. In addition, exogenous Tβ4 also increased IL-8 secretion and blocking of IL-8 with neutralizing antibodies decreased Tβ4-induced ASC proliferation, suggesting that IL-8 is a critical mediator of Tβ4-enhanced proliferation. Moreover, Tβ4 activated phosphorylation of ERK1/2 and increased the nuclear translocation of NF-κB. These observation provide that Tβ4 promotes the expansion of human ASCs via an IL-8-dependent mechanism that involves the ERK and NF-κB pathways. Therefore, Tβ4 could be used as a tool for MSC expansion in cell therapeutics. - Highlights: • This is fundamental information required to correlate Tβ4 with MSC expansion. • MSC expansion by Tβ4 is involved in enhancement of IL-8 and ERK/NF-κB pathway. • Tβ4 could be used as a tool for MSC expansion in cell therapeutics

Thymosin beta-4 promotes mesenchymal stem cell proliferation via an interleukin-8-dependent mechanism

Energy Technology Data Exchange (ETDEWEB)

Jeon, Byung-Joon [Department of Plastic and Reconstructive Surgery, Korea University Medical Center, Gojan 1-dong, Danwon-gu, Ansan-si, Gyeonggi-do 425-707 (Korea, Republic of); Yang, Yoolhee; Kyung Shim, Su [Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of); Yang, Heung-Mo [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of); Cho, Daeho, E-mail: cdhkor@sookmyung.ac.kr [Department of Life Science, Sookmyung Women' s University, Hyochangwon-gil 52, Yongsan-gu, Seoul 140-742 (Korea, Republic of); Ik Bang, Sa, E-mail: si55.bang@samsung.com [Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of)

2013-10-15

Mesenchymal stem cells (MSCs) hold great promise for the field of tissue regeneration. Because only a limited number of MSCs can be obtained from each donor site, it is important to establish standard methods for MSC expansion using growth and trophic factors. Thymosin β4 (Tβ4) is a novel trophic factor that has antimicrobial effects and the potential to promote tissue repair. Tβ4 is a ubiquitous, naturally-occurring peptide in the wound bed. Therefore, the relationship between Tβ4 and MSCs, especially adjacent adipose tissue-derived stem cells (ASCs), merits consideration. Exogenous Tβ4 treatment enhanced the proliferation of human ASCs, resulting in prominent nuclear localization of PCNA immunoreactivity. In addition, exogenous Tβ4 also increased IL-8 secretion and blocking of IL-8 with neutralizing antibodies decreased Tβ4-induced ASC proliferation, suggesting that IL-8 is a critical mediator of Tβ4-enhanced proliferation. Moreover, Tβ4 activated phosphorylation of ERK1/2 and increased the nuclear translocation of NF-κB. These observation provide that Tβ4 promotes the expansion of human ASCs via an IL-8-dependent mechanism that involves the ERK and NF-κB pathways. Therefore, Tβ4 could be used as a tool for MSC expansion in cell therapeutics. - Highlights: • This is fundamental information required to correlate Tβ4 with MSC expansion. • MSC expansion by Tβ4 is involved in enhancement of IL-8 and ERK/NF-κB pathway. • Tβ4 could be used as a tool for MSC expansion in cell therapeutics.

1α,25-Dihydroxyvitamin D(3) inhibits vascular cellular adhesion molecule-1 expression and interleukin-8 production in human coronary arterial endothelial cells.

Science.gov (United States)

Kudo, Keiko; Hasegawa, Shunji; Suzuki, Yasuo; Hirano, Reiji; Wakiguchi, Hiroyuki; Kittaka, Setsuaki; Ichiyama, Takashi

2012-11-01

Kawasaki disease is an acute febrile vasculitis of childhood that is associated with elevated production of inflammatory cytokines, causing damage to the coronary arteries. The production of proinflammatory cytokines and expression of adhesion molecules in human coronary arterial endothelial cells (HCAECs) is regulated by nuclear transcription factor-κB (NF-κB) activation. We have previously reported that the active form of vitamin D, 1α,25-dihydroxyvitamin D(3) (1α,25-(OH)(2)D(3)), inhibits tumor necrosis factor-α (TNF-α)-induced NF-κB activation. In this study, we examined the anti-inflammatory effects of 1α,25-(OH)(2)D(3) on TNF-α-induced adhesion molecule expression (vascular cellular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1)) and cytokine production (interleukin-6 (IL-6) and IL-8) in HCAECs. Pretreatment with 1α,25-(OH)(2)D(3) significantly inhibited TNF-α-induced VCAM-1 expression and IL-8 production in HCAECs. Our results suggest that adjunctive 1α,25-(OH)(2)D(3) therapy may modulate the inflammatory response during Kawasaki disease vasculitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Clinical significance of determination of changes of serum IGF-II, IL-6, IL-8 and hs-CRP levels after treatment in pediatric patients with bronchopneumonia

International Nuclear Information System (INIS)

Wang Guanghui; Chen Chuanbing; Wang Xianwu

2009-01-01

Objective: To explore the clinical significance of changes of serum IGF-II, IL-6, IL-8 and hs-CRP levels after treatment in pediatric patients with bronchopneumonia. Methods: Serum IGF-II, IL-6, IL-8 (with RIA) and hs-CRP (with immunoturbidity method) levels were determined in 36 pediatric patients with bronchopneumonia both before and after treatment as well as in 35 controls. Results: Before treatment, serum IGF-II, IL-6, IL-8 and hs-CRP levels in the patients were significantly higher than those in the controls (P 0.05). Conclusion: Determination of serum IGF-II, IL-6, IL-8 and hs-CRP levels in pediatric patients with bronchopneumonia was important for diagnosis and outcome prediction. (authors)

Clinical significance of measurement of changes of serum TNF-α, IL-6 and IL-8 centent after treatment in patients with pregnancy induced hypertension (PIH)

International Nuclear Information System (INIS)

Wang Guiying

2008-01-01

Objective: To explore the clinical significance of changes of serum TNF-α, IL-6 and IL-8 levels in patients with pregnancy induced hypertension. Methods: Serum TNF-α, IL-6 and IL-8 levels were measured with RIA in 36 patients with pregnancy induced hypertension both before and after 2 weeks of treatment as well as in 35 controls. Results: Before treatment, the serum TNF-α, IL-6 and IL-8 levels were significantly higher in patients with PIH than those in the controls (P 0.05). Conclusion: The inflammatory cytokines such as TNF-α, IL-6 and IL-8 may play important roles in the pathogenesis of pregnancy induced hypertension. (authors)

IL-17A acts via p38 MAPK to increase stability of TNF-alpha-induced IL-8 mRNA in human ASM.

Science.gov (United States)

Henness, Sheridan; van Thoor, Eveline; Ge, Qi; Armour, Carol L; Hughes, J Margaret; Ammit, Alaina J

2006-06-01

Human airway smooth muscle (ASM) plays an immunomodulatory role in asthma. Recently, IL-17A has become of increasing interest in asthma, being found at elevated levels in asthmatic airways and emerging as playing an important role in airway neutrophilia. IL-17A predominantly exerts its neutrophil orchestrating role indirectly via the induction of cytokines by resident airway structural cells. Here, we perform an in vitro study to show that although IL-17A did not induce secretion of the CXC chemokine IL-8 from ASM cells, IL-17A significantly potentiates TNF-alpha-induced IL-8 protein secretion and gene expression in a concentration- and time-dependent manner (P ASM cells, acting via a p38 MAPK-dependent posttranscriptional pathway to augment TNF-alpha-induced secretion of the potent neutrophil chemoattractant IL-8 from ASM cells.

Agonists and inverse agonists for the herpesvirus 8-encoded constitutively active seven-transmembrane oncogene product, ORF-74

DEFF Research Database (Denmark)

Rosenkilde, M M; Kledal, T N; Bräuner-Osborne, Hans

1999-01-01

A number of CXC chemokines competed with similar, nanomolar affinity against 125I-interleukin-8 (IL-8) binding to ORF-74, a constitutively active seven-transmembrane receptor encoded by human herpesvirus 8. However, in competition against 125I-labeled growth-related oncogene (GRO)-alpha, the ORF-74...

Deregulation of a STAT3-IL8 Signaling Pathway Promotes Human Glioblastoma Cell Proliferation and Invasiveness

Science.gov (United States)

de la Iglesia, Núria; Konopka, Genevieve; Lim, Kah Leong; Nutt, Catherine L.; Bromberg, Jacqueline F.; Frank, David A.; Mischel, Paul S.; Louis, David N.; Bonni, Azad

2009-01-01

Inactivation of the tumor suppressor PTEN is recognized as a major event in the pathogenesis of the brain tumor glioblastoma. However, the mechanisms by which PTEN loss specifically impacts the malignant behavior of glioblastoma cells including their proliferation and propensity for invasiveness remain poorly understood. Genetic studies suggest that the transcription factor STAT3 harbors a PTEN-regulated tumor suppressive function in mouse astrocytes. Here, we report that STAT3 plays a critical tumor suppressive role in PTEN-deficient human glioblastoma cells. Endogenous STAT3 signaling is specifically inhibited in PTEN-deficient glioblastoma cells. Strikingly, reactivation of STAT3 in PTEN-deficient glioblastoma cells inhibits their proliferation, invasiveness, and ability to spread on myelin. We also identify the chemokine IL8 as a novel target gene of STAT3 in human glioblastoma cells. Activated STAT3 occupies the endogenous IL8 promoter and directly represses IL8 transcription. Consistent with these results, IL8 is upregulated in PTEN-deficient human glioblastoma tumors. Importantly, IL8 repression mediates STAT3-inhibition of glioblastoma cell proliferation, invasiveness, and spreading on myelin. Collectively, our findings uncover a novel link between STAT3 and IL8 whose deregulation plays a key role in the malignant behavior of PTEN-deficient glioblastoma cells. These studies suggest that STAT3 activation or IL8 inhibition may have potential in patient-tailored treatment of PTEN-deficient brain tumors. PMID:18524891

Differential transcriptional regulation of IL-8 expression by human airway epithelial cells exposed to diesel exhaust particles

International Nuclear Information System (INIS)

Tal, Tamara L.; Simmons, Steven O.; Silbajoris, Robert; Dailey, Lisa; Cho, Seung-Hyun; Ramabhadran, Ram; Linak, William; Reed, William; Bromberg, Philip A.; Samet, James M.

2010-01-01

Exposure to diesel exhaust particles (DEP) induces inflammatory signaling characterized by MAP kinase-mediated activation of NFkB and AP-1 in vitro and in bronchial biopsies obtained from human subjects exposed to DEP. NFkB and AP-1 activation results in the upregulation of genes involved in promoting inflammation in airway epithelial cells, a principal target of inhaled DEP. IL-8 is a proinflammatory chemokine expressed by the airway epithelium in response to environmental pollutants. The mechanism by which DEP exposure induces IL-8 expression is not well understood. In the current study, we sought to determine whether DEP with varying organic content induces IL-8 expression in lung epithelial cells, as well as, to develop a method to rapidly evaluate the upstream mechanism(s) by which DEP induces IL-8 expression. Exposure to DEP with varying organic content differentially induced IL-8 expression and IL-8 promoter activity human airway epithelial cells. Mutational analysis of the IL-8 promoter was also performed using recombinant human cell lines expressing reporters linked to the mutated promoters. Treatment with a low organic-containing DEP stimulated IL-8 expression by a mechanism that is predominantly NFkB-dependent. In contrast, exposure to high organic-containing DEP induced IL-8 expression independently of NFkB through a mechanism that requires AP-1 activity. Our study reveals that exposure to DEP of varying organic content induces proinflammatory gene expression through multiple specific mechanisms in human airway epithelial cells. The approaches used in the present study demonstrate the utility of a promoter-reporter assay ensemble for identifying transcriptional pathways activated by pollutant exposure.

Differential NF-κB and MAPK activation underlies fluoride- and TPA-mediated CXCL8 (IL-8 induction in lung epithelial cells

Directory of Open Access Journals (Sweden)

Refsnes M

2014-12-01

Full Text Available Magne Refsnes, Tonje Skuland, Marit Låg, Per E Schwarze, Johan Øvrevik Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway Abstract: Different toxic agents have a varying potential to induce the production of the proinflammatory chemokine, CXCL8 (interleukin [IL]-8, in lung cells. A critical question is which mechanisms determine the magnitude and persistence of the CXCL8 responses to different stimuli. To approach this, we compared the potential of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA, and sodium fluoride (NaF to induce CXCL8 responses in A549 cells, with emphasis on the importance of nuclear factor kappa B (NF-κB- and mitogen-activated protein kinase (MAPK signaling. Notably, TPA induced a greater release of CXCL8 than did NaF. Furthermore, TPA induced a strong, rapid, but transient upregulation of CXCL8 messenger (mRNA, whereas NaF induced a weaker, more delayed, but persistent upregulation. With respect to signaling, TPA led to an early, strong, and relatively transient extracellular signal-regulated kinase (ERK1/2 phosphorylation, and a less marked and even more transient phosphorylation of c-jun-N-terminal kinases (JNK1/2 and p38. In contrast, NaF elicited a lower, but relatively sustained increase in phosphorylation of ERK1/2, and a marked phosphorylation of p38 and JNK1/2, with the JNK1/2 response as most transient. Only ERK1/2 inhibition affected the TPA response, whereas inhibition of all the three MAPK cascades reduced NaF-induced CXCL8 release. TPA also induced an early, marked phosphorylation/translocation of p65 (NF-κB, whereas NaF induced slower, less pronounced effects on p65. The CXCL8 responses by TPA and NaF were reduced by p65-siRNA. In conclusion, all MAPK cascades were involved in NaF-induced CXCL8 release, whereas only ERK1/2 activation was involved in response to TPA. Furthermore, NF-κB activation appeared to be

Interleukin 8 in progression of hormone-dependent early breast cancer

Indian Academy of Sciences (India)

2017-04-18

Apr 18, 2017 ... significance of IL8 in hormone-dependent breast cancer. The aim of this study was to evaluate the prognostic ... types characterized by a particularly poor prognosis (Aceto et al. ... Progesterone receptor status. PRlow. 70. 76.9. PRhigh. 21. 23.1. NA .... (M<88.82 pg/mg) had lower percentage of relapses and.

p38 mitogen-activated protein kinase mediates IL-8 induction by the ribotoxin deoxynivalenol in human monocytes

International Nuclear Information System (INIS)

Islam, Zahidul; Gray, Jennifer S.; Pestka, James J.

2006-01-01

The effects of the ribotoxic trichothecene deoxynivalenol (DON) on mitogen-activated protein kinase (MAPK)-mediated IL-8 expression were investigated in cloned human monocytes and peripheral blood mononuclear cells (PBMC). DON (250 to 1000 ng/ml) induced both IL-8 mRNA and IL-8 heteronuclear RNA (hnRNA), an indicator of IL-8 transcription, in the human U937 monocytic cell line in a concentration-dependent manner. Expression of IL-8 hnRNA, mRNA and protein correlated with p38 phosphorylation and was completely abrogated by the p38 MAPK inhibitor SB203580. DON at 500 ng/ml similarly induced p38-dependent IL-8 protein and mRNA expression in PBMC cultures from healthy volunteers. Significantly increased IL-6 and IL-1β intracellular protein and mRNA expression was also observed in PBMC treated with DON (500 ng/ml) which were also partially p38-dependent. Flow cytometry of PBMC revealed that DON-induced p38 phosphorylation varied among individuals relative to both threshold toxin concentrations (25-100 ng/ml) and relative increases in percentages of phospho-p38 + cells. DON-induced p38 activation occurred exclusively in the CD14 + monocyte population. DON was devoid of agonist activity for human Toll-like receptors 2, 3, 4, 5, 7, 8 and 9. However, two other ribotoxins, emetine and anisomycin, induced p38 phosphorylation in PBMC similarly to DON. Taken together, these data suggest that (1) p38 activation was required for induction of IL-8 and proinflammatory gene expression in the monocyte and (2) DON induced p38 activation in human monocytes via the ribotoxic stress response

The change of endotoxin, TNF-α, IL-6 and IL-8 in rats with open abdominal wound and seawater immersion

International Nuclear Information System (INIS)

Jiang Tao; Han Shanqiao; Hu Ming; Wang Dapeng; Chen Yongpeng; Chen Liang; Yu Jiyao

2009-01-01

Objective: To observe the change of endotoxin (lipopolysaccharide, LPS), tumor necrosis factor-α (TNF-α), IL-6, IL-8 in plasma in rats with open abdominal wound and seawater immersion. Method: One hundred and sixteen adult Wistar rats were randomly divided into 2 groups, ninety-six in the group of open abdominal wound with seawater immersion and 20 in open abdominal wound group (control group). LPS, TNF-α, IL-6 and IL-8 in plasma were examined at 0.5 h, 1 h, 2 h, 3 h and 4 h after open abdominal wound and seawater immersion by rapid microorganism-testing device and gamma detectors. All data were analyzed with statistic software. Results: Compared with the control group, the LPS level in plasma increased with significantly 2-4 hours after the open abdominal wound with seawater immersion (P<0.05), the concentrations of TNF-α significantly increased 4 hours after seawater immersion, and the IL-6 concentrations significantly increased 3-4 hours after seawater immersion. There was no statistical difference in IL-8 concentrations between the two groups. Conclusion: Closely related to the injury, the marked increase in LPS, TNF-α and IL-6 in plasma is one of the main fetal causes of toxic shock. (authors)

Anti-IL-17 Antibody Improves Hepatic Steatosis by Suppressing Interleukin-17-Related Fatty Acid Synthesis and Metabolism

Directory of Open Access Journals (Sweden)

Weidong Shi

2013-01-01

Full Text Available To investigate the relationship between interleukin-17 and proteins involved in fatty acid metabolism with respect to alcoholic liver disease, male ICR mice were randomized into five groups: control, alcoholic liver disease (ALD at 4 weeks, 8 weeks, and 12 weeks, and anti-IL-17 antibody treated ALD. A proteomic approach was adopted to investigate changes in liver proteins between control and ALD groups. The proteomic analysis was performed by two-dimensional difference gel electrophoresis. Spots of interest were subsequently subjected to nanospray ionization tandem mass spectrometry (MS/MS for protein identification. Additionally, expression levels of selected proteins were confirmed by western blot. Transcriptional levels of some selected proteins were determined by RT-PCR. Expression levels of 95 protein spots changed significantly (ratio >1.5, P<0.05 during the development of ALD. Sterol regulatory element-binding protein-lc (SREBP-1c, carbohydrate response element binding protein (ChREBP, enoyl-coenzyme A hydratase (ECHS1, and peroxisome proliferator-activated receptor alpha (PPAR-α were identified by MS/MS among the proteins shown to vary the most; increased IL-17 elevated the transcription of SREBP-1c and ChREBP but suppressed ECHS1 and PPAR-α. The interleukin-17 signaling pathway is involved in ALD development; anti-IL-17 antibody improved hepatic steatosis by suppressing interleukin-17-related fatty acid metabolism.

TRAF2 regulates peripheral CD8(+) T-cell and NKT-cell homeostasis by modulating sensitivity to IL-15.

Science.gov (United States)

Villanueva, Jeanette E; Malle, Elisabeth K; Gardam, Sandra; Silveira, Pablo A; Zammit, Nathan W; Walters, Stacey N; Brink, Robert; Grey, Shane T

2015-06-01

In this study, a critical and novel role for TNF receptor (TNFR) associated factor 2 (TRAF2) is elucidated for peripheral CD8(+) T-cell and NKT-cell homeostasis. Mice deficient in TRAF2 only in their T cells (TRAF2TKO) show ∼40% reduction in effector memory and ∼50% reduction in naïve CD8(+) T-cell subsets. IL-15-dependent populations were reduced further, as TRAF2TKO mice displayed a marked ∼70% reduction in central memory CD8(+) CD44(hi) CD122(+) T cells and ∼80% decrease in NKT cells. TRAF2TKO CD8(+) CD44(hi) T cells exhibited impaired dose-dependent proliferation to exogenous IL-15. In contrast, TRAF2TKO CD8(+) T cells proliferated normally to anti-CD3 and TRAF2TKO CD8(+) CD44(hi) T cells exhibited normal proliferation to exogenous IL-2. TRAF2TKO CD8(+) T cells expressed normal levels of IL-15-associated receptors and possessed functional IL-15-mediated STAT5 phosphorylation, however TRAF2 deletion caused increased AKT activation. Loss of CD8(+) CD44(hi) CD122(+) and NKT cells was mechanistically linked to an inability to respond to IL-15. The reduced CD8(+) CD44(hi) CD122(+) T-cell and NKT-cell populations in TRAF2TKO mice were rescued in the presence of high dose IL-15 by IL-15/IL-15Rα complex administration. These studies demonstrate a critical role for TRAF2 in the maintenance of peripheral CD8(+) CD44(hi) CD122(+) T-cell and NKT-cell homeostasis by modulating sensitivity to T-cell intrinsic growth factors such as IL-15. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Muscle glycogen depletion following 75-km of cycling is not linked to increased muscle IL-6, IL-8, and MCP-1 mRNA expression and protein content

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David Christopher Nieman

2016-09-01

Full Text Available The cytokine response to heavy exertion varies widely for unknown reasons, and this study evaluated the relative importance of glycogen depletion, muscle damage, and stress hormone changes on blood and muscle cytokine measures. Cyclists (N=20 participated in a 75-km cycling time trial (168±26.0 min, with blood and vastus lateralis muscle samples collected before and after. Muscle glycogen decreased 77.2±17.4%, muscle IL-6, IL-8, and MCP-1 mRNA increased 18.5±2.8-, 45.3±7.8-, and 8.25±1.75-fold, and muscle IL-6, IL-8, and MCP-1 protein increased 70.5±14.1%, 347±68.1%, and 148±21.3%, respectively (all, P<0.001. Serum myoglobin and cortisol increased 32.1±3.3 to 242±48.3 mg/mL, and 295±27.6 to 784±63.5 nmol/L, respectively (both P<0.001. Plasma IL-6, IL-8, and MCP-1 increased 0.42±0.07 to 18.5±3.8, 4.07±0.37 to 17.0±1.8, and 96.5±3.7 to 240±21.6 pg/mL, respectively (all P<0.001. Increases in muscle IL-6, IL-8, and MCP-1 mRNA were unrelated to any of the outcome measures. Muscle glycogen depletion was related to change in plasma IL-6 (r=0.462, P=0.040, with change in myoglobin related to plasma IL-8 (r=0.582, P=0.007 and plasma MCP-1 (r=0.457, P=0.043, and muscle MCP-1 protein (r=0.588, P=0.017; cortisol was related to plasma IL-8 (r=0.613, P=0.004, muscle IL-8 protein (r=0.681, P=0.004, and plasma MCP-1 (r=0.442, P=0.050. In summary, this study showed that muscle IL-6, IL-8, and MCP-1 mRNA expression after 75-km cycling was unrelated to glycogen depletion and muscle damage, with change in muscle glycogen related to plasma IL-6, and changes in serum myoglobin and cortisol related to the chemotactic cytokines IL-8 and MCP-1.

Therapeutic Applications of Interleukin 24 (IL24): A Review ...

African Journals Online (AJOL)

IL24 has growth suppressive properties in a wide variety of human cancer cell lines without inducing harmful effects in normal cells. This review is focused on the role of IL 24 on tumor cell biology and its potential therapeutic applications. Keywords: Melanoma differentiation, Protein, Therapeutics, Interleukin, ...

Preclinical evaluation of technetium 99m-labeled P1827DS for infection imaging and comparison with technetium 99m IL-8

Energy Technology Data Exchange (ETDEWEB)

Krause, Sabine [Bayer Schering Pharma AG, Global Drug Discovery, D-13342 Berlin (Germany); Rennen, Huub J.; Boerman, Otto C. [Radboud University, Nijmegen Medical Centre, 6500 HB Nijmegen (Netherlands); Baumann, Sabine; Cyr, John E.; Manchanda, Rajesh; Lister-James, John [Bayer Schering Pharma AG, Global Drug Discovery, D-13342 Berlin (Germany); Corstens, Frans C. [Radboud University, Nijmegen Medical Centre, 6500 HB Nijmegen (Netherlands); Dinkelborg, Ludger M. [Bayer Schering Pharma AG, Global Drug Discovery, D-13342 Berlin (Germany)], E-mail: sabine.krause@bayerhealthcare.com

2007-11-15

Background: The technetium 99 m ({sup 99m}Tc)-radiolabeled, leukocyte-avid peptide-glycoseaminoglycan complex, [{sup 99m}Tc]P1827DS, has been synthesized as an improved infection/inflammation imaging agent to [{sup 99m}Tc]P483H (LeukoTect, Diatide). In a phase I/II clinical trail, [{sup 99m}Tc]P483H images were equivalent to those obtained with {sup 111}In ex vivo labeled leukocytes. However, there was physiologic accumulation of radioactivity in the body that could hamper interpretation of the images. In this study, the potential of [{sup 99m}Tc]P1827DS for infection imaging was assessed in comparison with [{sup 99m}Tc]P483H and the well-described imaging agent [{sup 99m}Tc] hydrazinonicotinamide (HYNIC)-interleukin 8 (IL-8). Methods: The binding of [{sup 99m}Tc]P1827DS to human blood cell was studied in vitro. A rabbit Escherichia coli infection model was used to perform the biodistribution and imaging studies with [{sup 99m}Tc]P1827DS, [{sup 99m}Tc]P483H and [{sup 99m}Tc]HYNIC-IL-8. Results: [{sup 99m}Tc]P1827DS binds to leukocytes but not to erythrocytes. The leukocyte binding was not saturable up to an investigated concentration of 10 {mu}M. The accumulation of [{sup 99m}Tc]P1827/DS at the infection site strongly depends on the P1827/DS ratio and was optimal at a molar ratio of 10:1. [{sup 99m}Tc]P1827DS shows improved biodistribution over [{sup 99m}Tc]P483H with similar uptake at the infection site. Abscess uptake of [{sup 99m}Tc]HYNIC-IL-8 was approximately three times higher than that of [{sup 99m}Tc]P1827DS. [{sup 99m}Tc]HYNIC-IL-8 showed high accumulation in the kidneys, whereas [{sup 99m}Tc]P1827DS showed high lung uptake and slightly higher accumulation in the liver and spleen. Conclusion: [{sup 99m}Tc]P1827DS is a potential new inflammation imaging agent, which clearly visualized the abscess in the rabbit E. coli infection model and showed improved biodistribution compared to [{sup 99m}Tc]P483H. However, the infection uptake and biodistribution of

Preclinical evaluation of technetium 99m-labeled P1827DS for infection imaging and comparison with technetium 99m IL-8

International Nuclear Information System (INIS)

Krause, Sabine; Rennen, Huub J.; Boerman, Otto C.; Baumann, Sabine; Cyr, John E.; Manchanda, Rajesh; Lister-James, John; Corstens, Frans C.; Dinkelborg, Ludger M.

2007-01-01

Background: The technetium 99 m ( 99m Tc)-radiolabeled, leukocyte-avid peptide-glycoseaminoglycan complex, [ 99m Tc]P1827DS, has been synthesized as an improved infection/inflammation imaging agent to [ 99m Tc]P483H (LeukoTect, Diatide). In a phase I/II clinical trail, [ 99m Tc]P483H images were equivalent to those obtained with 111 In ex vivo labeled leukocytes. However, there was physiologic accumulation of radioactivity in the body that could hamper interpretation of the images. In this study, the potential of [ 99m Tc]P1827DS for infection imaging was assessed in comparison with [ 99m Tc]P483H and the well-described imaging agent [ 99m Tc] hydrazinonicotinamide (HYNIC)-interleukin 8 (IL-8). Methods: The binding of [ 99m Tc]P1827DS to human blood cell was studied in vitro. A rabbit Escherichia coli infection model was used to perform the biodistribution and imaging studies with [ 99m Tc]P1827DS, [ 99m Tc]P483H and [ 99m Tc]HYNIC-IL-8. Results: [ 99m Tc]P1827DS binds to leukocytes but not to erythrocytes. The leukocyte binding was not saturable up to an investigated concentration of 10 μM. The accumulation of [ 99m Tc]P1827/DS at the infection site strongly depends on the P1827/DS ratio and was optimal at a molar ratio of 10:1. [ 99m Tc]P1827DS shows improved biodistribution over [ 99m Tc]P483H with similar uptake at the infection site. Abscess uptake of [ 99m Tc]HYNIC-IL-8 was approximately three times higher than that of [ 99m Tc]P1827DS. [ 99m Tc]HYNIC-IL-8 showed high accumulation in the kidneys, whereas [ 99m Tc]P1827DS showed high lung uptake and slightly higher accumulation in the liver and spleen. Conclusion: [ 99m Tc]P1827DS is a potential new inflammation imaging agent, which clearly visualized the abscess in the rabbit E. coli infection model and showed improved biodistribution compared to [ 99m Tc]P483H. However, the infection uptake and biodistribution of [ 99m Tc]P1827DS is not superior to that of [ 99m Tc]HYNIC-IL-8 in this animal model

Cortisol, Interleukins and S100B in Delirium in the Elderly

Science.gov (United States)

van Munster, Barbara C.; Bisschop, Peter H.; Zwinderman, Aeilko H.; Korevaar, Johanna C.; Endert, Erik; Wiersinga, W. Joost; van Oosten, Hannah E.; Goslings, J. Carel; de Rooij, Sophia E. J. A.

2010-01-01

In independent studies delirium was associated with higher levels of cortisol, interleukin(IL)s, and S100B. The aim of this study was to simultaneously compare cortisol, IL-6, IL-8, and S100B levels in patients aged 65 years and older admitted for hip fracture surgery with and without delirium. Cortisol, IL-6, IL-8, and S100B were assayed in…

Polymorphisms of TNF-α -308 G/A and IL-8 -251 T/A Genes Associated with Urothelial Carcinoma: A Case-Control Study

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Chia-Chang Wu

2018-01-01

Full Text Available Cigarette smoking and exposure to environmental tobacco smoke are well-known risk factors for urothelial carcinoma (UC. We conducted a hospital-based case-control study involving 287 UC cases and 574 cancer-free controls to investigate the joint effects of cigarette smoking and polymorphisms of inflammatory genes on UC risk. Tumor necrosis factor alpha (TNF-α -308 G/A and interleukin-8 (IL-8 -251 T/A polymorphisms were determined using a polymerase chain reaction-restriction fragment length polymorphism method. People who had ever smoked and those who were exposed to environmental tobacco smoke had significantly increased UC odds ratios (ORs of 1.65 and 1.68, respectively. Participants who had smoked more than 18 pack-years had a significantly increased UC OR of 2.64. People who had ever smoked and who carried the A/A genotype of the TNF-α -308 G/A polymorphism had a significantly higher UC OR (10.25 compared to people who had never smoked and who carried the G/G or G/A genotype. In addition, people who had ever smoked and who carried the IL-8 -251 T/T genotype had a significantly increased UC OR (3.08 compared to people who had never smoked and who carried the T/A or A/A genotype. In a combined analysis of three major risk factors (cumulative cigarette smoking, the TNF-α -308 A/A genotype, and the IL-8 -251 T/T genotype, subjects with any one, any two, and all three risk factors experienced significantly increased UC ORs of 1.55, 2.89, and 3.77, respectively, compared to individuals with none of the risk factors. Conclusions. Our results indicate that the combined effects of cumulative cigarette exposure and the TNF-α -308 A/A genotype and/or the IL-8 -251 T/T genotype on UC OR showed a significant dose-response relationship.

Effect of intramammary infusion of recombinant bovine GM-CSF and IL-8 on CMT score, somatic cell count, and milk mononuclear cell populations in Holstein cows with Staphylococcus aureus subclinical mastitis.

Science.gov (United States)

Kiku, Yoshio; Ozawa, Tomomi; Takahashi, Hideyuki; Kushibiki, Shiro; Inumaru, Shigeki; Shingu, Hiroyuki; Nagasawa, Yuya; Watanabe, Atsushi; Hata, Eiji; Hayashi, Tomohito

2017-09-01

The effect of intramammary infusion of recombinant bovine granulocyte-macrophage colony-stimulating factor (rbGM-CSF) and interleukin-8 (rbIL-8) on mononuclear cell populations in quarters, somatic cell count (SCC) and the California Mastitis Test (CMT) score were investigated. From the selected cows with naturally occurring Staphylococcus aureus subclinical mastitis, one quarter of each cow were selected for the infusions of rbGM-CSF (400 μg/5 mL/quarter, n = 9), rbIL-8 (1 mg/5 mL/quarter, n = 9), and phosphate-buffered saline (5 mL/quarter, n = 7). The CMT score of both cytokines post infusion temporarily increased between days 0 and 1 and significantly decreased between days 7 and 14 compared to the preinfusion level. The SCC on day 14 after infusions of rbGM-CSF tended to be lower than that of the control group. The percentage of CD14+ cells increased on days 1 and 2 post infusion of rbGM-CSF. The percentage of CD4+ and CD8+ cells also increased on days 2 and 3, suggesting that the infusion of rbGM-CSF enhanced cellular immunity in the mammary gland. In contrast, the percentage of CD14+ cells decreased on days 0.25 and 1 post infusion of rbIL-8. No significant changes in the percentages of CD4+ and CD8+ cells in milk after infusion of rbIL-8 were evident during the experimental period, which suggested that rbIL-8 had little effect on the function of T cells in the mammary gland. These results indicated that rbGM-CSF and rbIL-8 decreased the CMT score by a different mechanism and may have a potential as therapeutic agents for subclinical mastitis.

α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8.

LENUS (Irish Health Repository)

Bergin, David A

2010-12-01

Hereditary deficiency of the protein α-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung. However, the reason for the increased neutrophil burden has not been fully elucidated. In this study we have demonstrated using human neutrophils that serum AAT coordinates both CXCR1- and soluble immune complex (sIC) receptor-mediated chemotaxis by divergent pathways. We demonstrated that glycosylated AAT can bind to IL-8 (a ligand for CXCR1) and that AAT-IL-8 complex formation prevented IL-8 interaction with CXCR1. Second, AAT modulated neutrophil chemotaxis in response to sIC by controlling membrane expression of the glycosylphosphatidylinositol-anchored (GPI-anchored) Fc receptor FcγRIIIb. This process was mediated through inhibition of ADAM-17 enzymatic activity. Neutrophils isolated from clinically stable AAT-deficient patients were characterized by low membrane expression of FcγRIIIb and increased chemotaxis in response to IL-8 and sIC. Treatment of AAT-deficient individuals with AAT augmentation therapy resulted in increased AAT binding to IL-8, increased AAT binding to the neutrophil membrane, decreased FcγRIIIb release from the neutrophil membrane, and normalization of chemotaxis. These results provide new insight into the mechanism underlying the effect of AAT augmentation therapy in the pulmonary disease associated with AAT deficiency.

Performance of Interleukin-6 and Interleukin-8 serum levels in pediatric oncology patients with neutropenia and fever for the assessment of low-risk

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Kontny Udo

2008-03-01

Full Text Available Abstract Background Patients with chemotherapy-related neutropenia and fever are usually hospitalized and treated on empirical intravenous broad-spectrum antibiotic regimens. Early diagnosis of sepsis in children with febrile neutropenia remains difficult due to non-specific clinical and laboratory signs of infection. We aimed to analyze whether IL-6 and IL-8 could define a group of patients at low risk of septicemia. Methods A prospective study was performed to assess the potential value of IL-6, IL-8 and C-reactive protein serum levels to predict severe bacterial infection or bacteremia in febrile neutropenic children with cancer during chemotherapy. Statistical test used: Friedman test, Wilcoxon-Test, Kruskal-Wallis H test, Mann-Whitney U-Test and Receiver Operating Characteristics. Results The analysis of cytokine levels measured at the onset of fever indicated that IL-6 and IL-8 are useful to define a possible group of patients with low risk of sepsis. In predicting bacteremia or severe bacterial infection, IL-6 was the best predictor with the optimum IL-6 cut-off level of 42 pg/ml showing a high sensitivity (90% and specificity (85%. Conclusion These findings may have clinical implications for risk-based antimicrobial treatment strategies.

Study on the serum EMAb, TNF-α, IL-8 and CA-125 levels in patients with endometriosis

International Nuclear Information System (INIS)

Hou Shuping; Han Ke

2006-01-01

Objective: To study the serum antiendometrium antibody (EMAb), TNF-α, IL-8 and CA-125 levels in patients with endometriosis. Methods: Serum EMAb levels were measured with ELISA and TNF-α, IL-8, CA-125 levels with RIA in 45 patients with histologically proven endometriosis and 35 controls. Results: The positive rate of serum EMAb was significantly higher in the patients with endometriosis than that in controls (P<0.01), Serum TNF-α, IL-8 and CA-125 levels were also significantly higher in the patients than those in controls (P<0.01). Combined measurement of these four markers would yield diagnostic sensitivity and spceificity higher than those from any single marker. In addition, levels of TNF-α, IL-8 and CA-125 in patients with advanced diseases were significantly higher than those in patients with mild diseases. Conclusion: Combined detection of serum EMAb positive rate and TNF-α, IL-8 and CA-125 levels were of clinical diagnostic value in patients with endometriosis. (authors)

Decreased Pulmonary Function in School Children in Western Japan after Exposures to Asian Desert Dusts and Its Association with Interleukin-8

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Masanari Watanabe

2015-01-01

Full Text Available The objective of the study was to investigate the influence of Asian dust storms (ADS on pulmonary function of school children and the relationship of this effect with interleukin-8. Morning peak expiratory flow (PEF was measured daily in 399 children from April to May 2012 and in 384 of these children from March to May 2013. The data were analyzed for an association between ADS events and PEF by linear mixed models. Interleukin-8 transcriptional activity was assessed in THP-G8 cells stimulated by airborne particles collected on ADS days. Seven ADS days were identified: April 23 and 24, 2012; March 8 to 10, 2013; and March 19 and 20, 2013. Changes in PEF after ADS exposure were −8.17 L/min (95% confidence interval, −11.40 to −4.93 in 2012 and −1.17 L/min (−4.07 to 1.74 in 2013, and there was a significant difference between 2012 and 2013. Interleukin-8 transcriptional activity was significantly higher in 2012 at 10.6±2.9-fold compared to 3.7±0.4 in March 8 to 10, 2013, and 2.3±0.2 in March 19 and 20, 2013. The influence of ADS events on pulmonary function of children differs with each ADS event and may be related to interleukin-8 production.

Decreased Pulmonary Function in School Children in Western Japan after Exposures to Asian Desert Dusts and Its Association with Interleukin-8

Science.gov (United States)

Watanabe, Masanari; Kurai, Jun; Sano, Hiroyuki; Saito, Rumiko; Kimura, Yutaka; Aiba, Setsuya; Oshimura, Mitsuo; Yamasaki, Akira; Shimizu, Eiji

2015-01-01

The objective of the study was to investigate the influence of Asian dust storms (ADS) on pulmonary function of school children and the relationship of this effect with interleukin-8. Morning peak expiratory flow (PEF) was measured daily in 399 children from April to May 2012 and in 384 of these children from March to May 2013. The data were analyzed for an association between ADS events and PEF by linear mixed models. Interleukin-8 transcriptional activity was assessed in THP-G8 cells stimulated by airborne particles collected on ADS days. Seven ADS days were identified: April 23 and 24, 2012; March 8 to 10, 2013; and March 19 and 20, 2013. Changes in PEF after ADS exposure were −8.17 L/min (95% confidence interval, −11.40 to −4.93) in 2012 and −1.17 L/min (−4.07 to 1.74) in 2013, and there was a significant difference between 2012 and 2013. Interleukin-8 transcriptional activity was significantly higher in 2012 at 10.6 ± 2.9-fold compared to 3.7 ± 0.4 in March 8 to 10, 2013, and 2.3 ± 0.2 in March 19 and 20, 2013. The influence of ADS events on pulmonary function of children differs with each ADS event and may be related to interleukin-8 production. PMID:26060816

Internalization of interleukin 1 (IL 1) correlates with IL 1-induced IL 2 receptor expression and IL 2 secretion of EL4 thymoma cells

OpenAIRE

Von Hoegen, I.; Falk, Werner; Kojouharoff, G.; Krammer, P. H.

1989-01-01

The cytokine interleukin 1 (IL 1) plays an important role in the induction of IL 2 secretion and high-affinity IL 2 receptor (IL 2R) expression by T cells. The events that follow binding of IL 1 to IL 1R, however, are still unknown. In this study we describe two variants of the murine thymoma EL4 (5D3 and D6/76) that express comparable numbers of cell surface IL 1 receptors and bind IL 1 with the same affinity, but show distinct IL 1-dependent IL 2 secretion and IL 2R expression. In the prese...

A novel bacterial transport mechanism of Acinetobacter baumannii via activated human neutrophils through interleukin-8.

Science.gov (United States)

Kamoshida, Go; Tansho-Nagakawa, Shigeru; Kikuchi-Ueda, Takane; Nakano, Ryuichi; Hikosaka, Kenji; Nishida, Satoshi; Ubagai, Tsuneyuki; Higashi, Shouichi; Ono, Yasuo

2016-12-01

Hospital-acquired infections as a result of Acinetobacter baumannii have become problematic because of high rates of drug resistance. Although neutrophils play a critical role in early protection against bacterial infection, their interactions with A. baumannii remain largely unknown. To elucidate the interactions between A. baumannii and human neutrophils, we cocultured these cells and analyzed them by microscopy and flow cytometry. We found that A. baumannii adhered to neutrophils. We next examined neutrophil and A. baumannii infiltration into Matrigel basement membranes by an in vitro transmigration assay. Neutrophils were activated by A. baumannii, and invasion was enhanced. More interestingly, A. baumannii was transported together by infiltrating neutrophils. Furthermore, we observed by live cell imaging that A. baumannii and neutrophils moved together. In addition, A. baumannii-activated neutrophils showed increased IL-8 production. The transport of A. baumannii was suppressed by inhibiting neutrophil infiltration by blocking the effect of IL-8. A. baumannii appears to use neutrophils for transport by activating these cells via IL-8. In this study, we revealed a novel bacterial transport mechanism that A. baumannii exploits human neutrophils by adhering to and inducing IL-8 release for bacterial portage. This mechanism might be a new treatment target. © Society for Leukocyte Biology.

Endogenous interleukin (IL)-17A promotes pristane-induced systemic autoimmunity and lupus nephritis induced by pristane.

Science.gov (United States)

Summers, S A; Odobasic, D; Khouri, M B; Steinmetz, O M; Yang, Y; Holdsworth, S R; Kitching, A R

2014-06-01

Interleukin (IL)-17A is increased both in serum and in kidney biopsies from patients with lupus nephritis, but direct evidence of pathogenicity is less well established. Administration of pristane to genetically intact mice results in the production of autoantibodies and proliferative glomerulonephritis, resembling human lupus nephritis. These studies sought to define the role of IL-17A in experimental lupus induced by pristane administration. Pristane was administered to wild-type (WT) and IL-17A(-/-) mice. Local and systemic immune responses were assessed after 6 days and 8 weeks, and autoimmunity, glomerular inflammation and renal injury were measured at 7 months. IL-17A production increased significantly 6 days after pristane injection, with innate immune cells, neutrophils (Ly6G(+)) and macrophages (F4/80(+)) being the predominant source of IL-17A. After 8 weeks, while systemic IL-17A was still readily detected in WT mice, the levels of proinflammatory cytokines, interferon (IFN)-γ and tumour necrosis factor (TNF) were diminished in the absence of endogenous IL-17A. Seven months after pristane treatment humoral autoimmunity was diminished in the absence of IL-17A, with decreased levels of immunoglobulin (Ig)G and anti-dsDNA antibodies. Renal inflammation and injury was less in the absence of IL-17A. Compared to WT mice, glomerular IgG, complement deposition, glomerular CD4(+) T cells and intrarenal expression of T helper type 1 (Th1)-associated proinflammatory mediators were decreased in IL-17A(-/-) mice. WT mice developed progressive proteinuria, but functional and histological renal injury was attenuated in the absence of IL-17A. Therefore, IL-17A is required for the full development of autoimmunity and lupus nephritis in experimental SLE, and early in the development of autoimmunity, innate immune cells produce IL-17A. © 2014 British Society for Immunology.

Biocompatible micro-sized cell culture chamber for the detection of nanoparticle-induced IL8 promoter activity on a small cell population

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Oostingh Gertie

2011-01-01

Full Text Available Abstract In most conventional in vitro toxicological assays, the response of a complete cell population is averaged, and therefore, single-cell responses are not detectable. Such averaging might result in misinterpretations when only individual cells within a population respond to a certain stimulus. Therefore, there is a need for non-invasive in vitro systems to verify the toxicity of nanoscale materials. In the present study, a micro-sized cell culture chamber with a silicon nitride membrane (0.16 mm2 was produced for cell cultivation and the detection of specific cell responses. The biocompatibility of the microcavity chip (MCC was verified by studying adipogenic and neuronal differentiation. Thereafter, the suitability of the MCC to study the effects of nanoparticles on a small cell population was determined by using a green fluorescence protein-based reporter cell line. Interleukin-8 promoter (pIL8 induction, a marker of an inflammatory response, was used to monitor immune activation. The validation of the MCC-based method was performed using well-characterized gold and silver nanoparticles. The sensitivity of the new method was verified comparing the quantified pIL8 activation via MCC-based and standard techniques. The results proved the biocompatibility and the sensitivity of the microculture chamber, as well as a high optical quality due to the properties of Si3N4. The MCC-based method is suited for threshold- and time-dependent analysis of nanoparticle-induced IL8 promoter activity. This novel system can give dynamic information at the level of adherent single cells of a small cell population and presents a new non-invasive in vitro test method to assess the toxicity of nanomaterials and other compounds. PACS: 85.35.Be, 81.16.Nd, 87.18.Mp

Biocompatible micro-sized cell culture chamber for the detection of nanoparticle-induced IL8 promoter activity on a small cell population

Science.gov (United States)

Kohl, Yvonne; Oostingh, Gertie J.; Sossalla, Adam; Duschl, Albert; von Briesen, Hagen; Thielecke, Hagen

2011-08-01

In most conventional in vitro toxicological assays, the response of a complete cell population is averaged, and therefore, single-cell responses are not detectable. Such averaging might result in misinterpretations when only individual cells within a population respond to a certain stimulus. Therefore, there is a need for non-invasive in vitro systems to verify the toxicity of nanoscale materials. In the present study, a micro-sized cell culture chamber with a silicon nitride membrane (0.16 mm2) was produced for cell cultivation and the detection of specific cell responses. The biocompatibility of the microcavity chip (MCC) was verified by studying adipogenic and neuronal differentiation. Thereafter, the suitability of the MCC to study the effects of nanoparticles on a small cell population was determined by using a green fluorescence protein-based reporter cell line. Interleukin-8 promoter (pIL8) induction, a marker of an inflammatory response, was used to monitor immune activation. The validation of the MCC-based method was performed using well-characterized gold and silver nanoparticles. The sensitivity of the new method was verified comparing the quantified pIL8 activation via MCC-based and standard techniques. The results proved the biocompatibility and the sensitivity of the microculture chamber, as well as a high optical quality due to the properties of Si3N4. The MCC-based method is suited for threshold- and time-dependent analysis of nanoparticle-induced IL8 promoter activity. This novel system can give dynamic information at the level of adherent single cells of a small cell population and presents a new non-invasive in vitro test method to assess the toxicity of nanomaterials and other compounds. PACS: 85.35.Be, 81.16.Nd, 87.18.Mp

Vectorial secretion of interleukin-8 (IL-8 or CXCL8) mediates homeostatic effects on the intestinal epithelium via apically located CXCR1

NARCIS (Netherlands)

Baarlen, van Peter; Rossi, Oriana; Wells, Jerry

2014-01-01

CXCL8 is produced by many cell types including epithelial, endothelial, fibroblasts and macrophages in response to TLR recognition of microbe-associated molecular patterns (MAMPs) or inflammatory cytokines and recruits phagocytes from the vasculature to sites of infection via interaction with its

Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis

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Larissa Lazzarini Furlan

2017-11-01

Conclusions: This study highlighted the importance of the rs4073 variant of the interleukin 8 gene, regarding response to inhaled bronchodilators, and of the assessment of mutations in the cystic fibrosis transmembrane conductance regulator gene.

Antiinflammatory properties of a peptide derived from interleukin-4

DEFF Research Database (Denmark)

Klementiev, Boris; Enevoldsen, Maj N; Li, Shizhong

2013-01-01

Interleukin-4 (IL-4) is a potent antiinflammatory cytokine. However its use in the clinic is hampered by side effects. We here describe the identification of a novel synthetic peptide, termed Ph8, derived from α-helix C of IL-4, which interacts with IL-4 receptor α (IL-4Rα). Employing various...... and reduced acute inflammation in carrageenan-induced edema. Our findings indicate that Ph8 is a promising potential drug candidate for the treatment of inflammatory diseases....

Recombinant human growth-regulated oncogene-alpha induces T lymphocyte chemotaxis. A process regulated via IL-8 receptors by IFN-gamma, TNF-alpha, IL-4, IL-10, and IL-13

DEFF Research Database (Denmark)

Jinquan, T; Frydenberg, Jane; Mukaida, N

1995-01-01

receptors on the cells. This process can be augmented by IFN-gamma and TNF-alpha, and inhibited by IL-4, IL-10, and IL-13. In addition, we also document that on T lymphocytes there exist IL-8 receptors that can be up-regulated by IFN-gamma, TNF-alpha, and IL-2. Our results demonstrate that rhGRO-alpha gene...

The effects of colloids or crystalloids on acute respiratory distress syndrome in swine (Sus scrofa models with severe sepsis: analysis on extravascular lung water, IL-8, and VCAM-1

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Rismala Dewi

2016-04-01

Full Text Available Background: Acute respiratory distress syndrome (ARDS is a fatal complication of severe sepsis. Due to its higher molecular weight, the use of colloids in fluid resuscitation may be associated with fewer cases of ARDS compared to crystalloids. Extravascular lung water (EVLW elevation and levels of interleukin-8 (IL-8 and vascular cell adhesion molecule-1 (VCAM-1 have been studied as indicators playing a role in the pathogenesis of ARDS. The aim of the study was to determine the effects of colloid or crystalloid on the incidence of ARDS, elevation of EVLW, and levels of IL-8 and VCAM-1, in swine models with severe sepsis.Methods: This was a randomized trial conducted at the Laboratory of Experimental Surgery, School of Veterinary Medicine, IPB, using 22 healthy swine models with a body weight of 8 to 12 kg. Subjects were randomly allocated to receive either colloid or crystalloid fluid resuscitation. After administration of endotoxin, clinical signs of ARDS, EVLW, IL-8, and VCAM-1 were monitored during sepsis, severe sepsis, and one- and three hours after fluid resuscitation. Analysis of data using the Wilcoxon test , Kolmogorov-Smirnov test, Mann-Whitney test, unpaired t test.Results: Mild ARDS was more prevalent in the colloid group, while moderate ARDS was more frequent in the crystalloid group. EVLW elevation was lower in the colloid compared to the crystalloid group. There was no significant difference in IL-8 and VCAM-1 levels between the two groups.Conclusion: The use of colloids in fluid resuscitation does not decrease the probability of ARDS events compared to crystalloids. Compared to crystalloids, colloids are associated with a lower increase in EVLWI, but not with IL-8 or VCAM-1 levels.

Effect of Lipoglycans from Mycobacterium Chelonae on the expression of inflammatory factors IL-8 and IL-6 in human corneal epithelial cells and its possible signal transduction pathway

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Chun-Zhou Tang

2015-06-01

Full Text Available AIM: To study the influence of Lipoglycans from Mycobacterium Chelonae(Cheon the expression of IL-6 and IL-8 in human corneal epithelia cells and its possible signal transduction pathway.METHODS: Lipoglycans was extracted by the Triton X-114 phase partitioning. Lipoglycans from Che were purified, by successive detergent and phenol extractions. Lipoglycans were separated by gel filtration on a Sephacryl 200 column and Sephacryl 100 column in series, followed by extensive dialisis. Purified Lipoglycans(50μg/mLwere added into culture medium to stimulate primary human corneal epithelial(HCEcells. Cells and supernatant were collected at 0, 6, 12, 24h after the stimulation. The IL-6 and IL-8 expression at mRNA level was assayed by using real time RT-PCR and the secreted IL-6 and IL-8 in the supernatants was measured by ELISA. Immunochemistry was used to detect the expression and location of NF-κB in HCE cells.RESULTS: After the treatment of Lipoglycans, the expression of IL-8 and IL-6 at mRNA level obviouly increased within 12h, and reached peak level at 6h(IL-8 was 36.8 times that of the blank control, and IL-6 was 32.7 times. Compared with the blank control group, the expression of IL-8 at protein level in the supernatant increased 2.8 folds at 6h(P>0.05, 13.4 folds at 12h(PPPPPCONCLUSION: Lipoglycans from Che can induce HCE cells to produce inflammatory factors(IL-6 and IL-8, and its signal transduction pathway probably is mediated by NF-κB.

A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control

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Gang Xin

2015-11-01

Full Text Available Control of chronic viral infections by CD8 T cells is critically dependent on CD4 help. In particular, helper-derived IL-21 plays a key role in sustaining the CD8 T cell response; however, the molecular pathways by which IL-21 sustains CD8 T cell immunity remain unclear. We demonstrate that IL-21 causes a phenotypic switch of transcription factor expression in CD8 T cells during chronic viral infection characterized by sustained BATF expression. Importantly, BATF expression during chronic infection is both required for optimal CD8 T cell persistence and anti-viral effector function and sufficient to rescue “unhelped” CD8 T cells. Mechanistically, BATF sustains the response by cooperating with IRF4, an antigen-induced transcription factor that is also critically required for CD8 T cell maintenance, to preserve Blimp-1 expression and thereby sustain CD8 T cell effector function. Collectively, these data suggest that CD4 T cells “help” the CD8 response during chronic infection via IL-21-induced BATF expression.

Significance of determination of serum IL-8 and interferon induced protein-10 (IP-10) contents in patients with psoriasis

International Nuclear Information System (INIS)

Yang Shijun; Cui Jianhe; Xue Mei

2005-01-01

Objective: To explore the roles played by IL-8 and IP-10 in the development and pathogenesis of psoriasis. Methods: Serum IL-8 (with RIA) and IP-10 (with ELISA) contents were measured in 47 patients with psoriasis and 42 controls. Results: The serum contents of IL-8 and IP-10 were significantly higher in the patients with psoriasis than those in the controls (P<0.01). Conclusion: IL-8 and IP-10 participated in the pathogenesis of psoriasis. Possible mechanisms were discussed. (authors)

IL-5-stimulated eosinophils adherent to periostin undergo stereotypic morphological changes and ADAM8-dependent migration.

Science.gov (United States)

Johansson, M W; Khanna, M; Bortnov, V; Annis, D S; Nguyen, C L; Mosher, D F

2017-10-01

IL-5 causes suspended eosinophils to polarize with filamentous (F)-actin and granules at one pole and the nucleus in a specialized uropod, the "nucleopod," which is capped with P-selectin glycoprotein ligand-1 (PSGL-1). IL-5 enhances eosinophil adhesion and migration on periostin, an extracellular matrix protein upregulated in asthma by type 2 immunity mediators. Determine how the polarized morphology evolves to foster migration of IL-5-stimulated eosinophils on a surface coated with periostin. Blood eosinophils adhering to adsorbed periostin were imaged at different time points by fluorescent microscopy, and migration of eosinophils on periostin was assayed. After 10 minutes in the presence of IL-5, adherent eosinophils were polarized with PSGL-1 at the nucleopod tip and F-actin distributed diffusely at the opposite end. After 30-60 minutes, the nucleopod had dissipated such that PSGL-1 was localized in a crescent or ring away from the cell periphery, and F-actin was found in podosome-like structures. The periostin layer, detected with monoclonal antibody Stiny-1, shown here to recognize the FAS1 4 module, was cleared in wide areas around adherent eosinophils. Clearance was attenuated by metalloproteinase inhibitors or antibodies to disintegrin metalloproteinase 8 (ADAM8), a major eosinophil metalloproteinase previously implicated in asthma pathogenesis. ADAM8 was not found in podosome-like structures, which are associated with proteolytic activity in other cell types. Instead, immunoblotting demonstrated proteoforms of ADAM8 that lack the cytoplasmic tail in the supernatant. Anti-ADAM8 inhibited migration of IL-5-stimulated eosinophils on periostin. Migrating IL-5-activated eosinophils on periostin exhibit loss of nucleopodal features and appearance of prominent podosomes along with clearance of the Stiny-1 periostin epitope. Migration and epitope clearance are both attenuated by inhibitors of ADAM8. We propose, therefore, that eosinophils remodel and migrate

Relationship between Emotion, Severity of Illness and the Effect on IL-8 in Asthmatic Children%儿童情绪与哮喘病情的关系及对IL-8的影响

Institute of Scientific and Technical Information of China (English)

牛轶; 程自立; 王高华; 姜毅

2002-01-01

Objective: To examine the emotional states o f asthmatic children wit h different degrees of severity, as well as the effects of emotion on change of cytokines in airway. Methods: Asthmatic children were divi ded into two groups ac cording to the degrees of severity: moderate and mild. Their emotional states we re measured and results were compared. Correlation analysis was conducted betwee n scores on emotional scales and sputum levels of IL-8.Results: Total scores on anxiety and depression were higher in the moderate group than in the mild group. Negative correlation was found between levels of anxiety and IL-8 during acute exacerbation of asthmatic condition. Conclusion: Emotional distress was found to be increased with severity of asthmatic condition in children. Anxiety contribu ted to the decreased concentration of IL-8 in asthmatic children's airway.

MCPIP-1, alias Regnase-1 controls epithelial inflammation by post-transcriptional regulation of IL-8 production

Science.gov (United States)

Dobosz, E.; Wilamowski, M.; Lech, M.; Bugara, B.; Jura, J.; Potempa, J.; Koziel, J.

2016-01-01

Pattern recognition receptors are critical for the detection of invading microorganisms. They activate multiple pathways that lead to the induction of pro-inflammatory responses and pathogen clearance. The intensity and duration of this immune reaction must be tightly controlled spatially and temporally in every tissue by different negative regulators. We hypothesized that monocyte chemoattractant protein-1–induced protein-1 (MCPIP-1) might play a role in maintaining immune homeostasis in the epithelium both under physiological conditions and upon bacterial infection. To this end, we examined the distribution of MCPIP-1 transcript and protein in various tissues. The MCPIP-1 protein level was higher in epithelial cells than in myeloid cells. MCPIP-1 exerted RNase activity towards the IL-8 transcript and the life-span of IL-8 was determined by the presence of the stem-loops/hairpin (SL) structures at the 3′ UTR region of IL-8 mRNA. Moreover, using fully active, purified recombinant MCPIP-1 protein, we elucidated the mechanism by which MCPIP-1 controls the IL-8 mRNA level. In conclusion, we uncovered a novel IL-8–dependent mechanism via which MCPIP-1 maintains epithelial homeostasis. This study reveals for the first time that MCPIP-1 plays a crucial anti-inflammatory role not only in myeloid cells but also in epithelial cells. PMID:27513529

Cytotoxic potential of lung CD8(+) T cells increases with chronic obstructive pulmonary disease severity and with in vitro stimulation by IL-18 or IL-15.

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Freeman, Christine M; Han, MeiLan K; Martinez, Fernando J; Murray, Susan; Liu, Lyrica X; Chensue, Stephen W; Polak, Timothy J; Sonstein, Joanne; Todt, Jill C; Ames, Theresa M; Arenberg, Douglas A; Meldrum, Catherine A; Getty, Christi; McCloskey, Lisa; Curtis, Jeffrey L

2010-06-01

Lung CD8(+) T cells might contribute to progression of chronic obstructive pulmonary disease (COPD) indirectly via IFN-gamma production or directly via cytolysis, but evidence for either mechanism is largely circumstantial. To gain insights into these potential mechanisms, we analyzed clinically indicated lung resections from three human cohorts, correlating findings with spirometrically defined disease severity. Expression by lung CD8(+) T cells of IL-18R and CD69 correlated with severity, as did mRNA transcripts for perforin and granzyme B, but not Fas ligand. These correlations persisted after correction for age, smoking history, presence of lung cancer, recent respiratory infection, or inhaled corticosteroid use. Analysis of transcripts for killer cell lectin-like receptor G1, IL-7R, and CD57 implied that lung CD8(+) T cells in COPD do not belong to the terminally differentiated effector populations associated with chronic infections or extreme age. In vitro stimulation of lung CD8(+) T cells with IL-18 plus IL-12 markedly increased production of IFN-gamma and TNF-alpha, whereas IL-15 stimulation induced increased intracellular perforin expression. Both IL-15 and IL-18 protein expression could be measured in whole lung tissue homogenates, but neither correlated in concentration with spirometric severity. Although lung CD8(+) T cell expression of mRNA for both T-box transcription factor expressed in T cells and GATA-binding protein 3 (but not retinoic acid receptor-related orphan receptor gamma or alpha) increased with spirometric severity, stimulation of lung CD8(+) T cells via CD3epsilon-induced secretion of IFN-gamma, TNF-alpha, and GM-CSF, but not IL-5, IL-13, and IL-17A. These findings suggest that the production of proinflammatory cytokines and cytotoxic molecules by lung-resident CD8(+) T cells contributes to COPD pathogenesis.

IL-6, IL-8, MMP-2, MMP-9 are overexpressed in Fanconi anemia cells through a NF-κB/TNF-α dependent mechanism.

Science.gov (United States)

Epanchintsev, Alexey; Shyamsunder, Pavithra; Verma, Rama S; Lyakhovich, Alex

2015-12-01

Fanconi anemia (FA) is a rare autosomal recessive genetic disorder associated with a bone-marrow failure, genome instability, hypersensitivity to DNA crosslinking agents and a predisposition to cancer. Mutations have been documented in 16 FA genes that participate in the FA-BRCA DNA repair pathway, a fundamental pathway in the development of the disease and the presentation of its symptoms. FA cells have been characterized by an overproduction of cytokines, MAPKs, and Interleukins. Through this study we have identified the overexpression of additional secretory factors such as IL-6, IL-8, MMP-2, and MMP-9 in FA cells and in cells depleted of FANCA or FANCC and proved that their expression is under the control of NF-κB/TNF-α signaling pathways. We also demonstrated that these overexpressed secretory factors were effective in promoting the proliferation, migration, and invasion of surrounding tumor cells a fundamental event in the process of epithelial mesenchymal transition (EMT) and that they also modulated the expression of EMT markers such as E-cadherin and SNAIL. Overall our data suggest that the upregulation of EMT promoting factors in FA may contribute to predisposing FA patients to cancer, thereby providing new insights into possible therapeutic interventions. © 2014 Wiley Periodicals, Inc.

Staphylococcus epidermidis polysaccharide intercellular adhesin induces IL-8 expression in human astrocytes via a mechanism involving TLR2.

LENUS (Irish Health Repository)

Stevens, Niall T

2009-03-01

Staphylococcus epidermidis is an opportunistic biofilm-forming pathogen associated with neurosurgical device-related meningitis. Expression of the polysaccharide intercellular adhesin (PIA) on its surface promotes S. epidermidis biofilm formation. Here we investigated the pro-inflammatory properties of PIA against primary and transformed human astrocytes. PIA induced IL-8 expression in a dose- and\\/or time-dependent manner from U373 MG cells and primary normal human astrocytes. This effect was inhibited by depletion of N-acetyl-beta-d-glucosamine polymer from the PIA preparation with Lycopersicon esculentum lectin or sodium meta-periodate. Expression of dominant-negative versions of the TLR2 and TLR4 adaptor proteins MyD88 and Mal in U373 MG cells inhibited PIA-induced IL-8 production. Blocking IL-1 had no effect. PIA failed to induce IL-8 production from HEK293 cells stably expressing TLR4. However, in U373 MG cells which express TLR2, neutralization of TLR2 impaired PIA-induced IL-8 production. In addition to IL-8, PIA also induced expression of other cytokines from U373 MG cells including IL-6 and MCP-1. These data implicate PIA as an important immunogenic component of the S. epidermidis biofilm that can regulate pro-inflammatory cytokine production from human astrocytes, in part, via TLR2.

NO CHANGES IN SERUM CONCENTRATIONS OF INTERLEUKIN 10 (IL-10) AND INTERFERON γ (IF-γ) BEFORE AND AFTER TREATMENT OF THE THYROID EYE DISEASE (TED)

Science.gov (United States)

Laban-Gučeva, Nevenka; Antova, Magdalena; Bogoev, Milco

2007-01-01

TED is a severe eye disease leading in rare cases to decrease of sight, optic nerve compression and blindness. Recently, significant progresses in understanding the disease have been done. Nevertheless, the treatment of the disease, especially in its severe form remains challenging. Glucocorticoids (GC) have been the basis of the treatment for a long time. Orbital irradiation (OI) and optical decompression (OD) are also used in managing the severe forms of TED. Somatostatin, intravenous immunoglobulin have been also used, with conflicting results. Regarding the potential for the treatment of TED with cytokine antagonists, controlled clinical studies are not available. Since cytokines play an important role in the pathogenesis of the TED, they seemed to be logical choice for modern TED treatment. It has been shown that both Th1 (interleukin-2, tumor necrosis factor γ, interleukin γ) and Th2 (interleukin-4,-5-,-10) profile T cells are activated in the TED. We therefore measured interleukin-γ, IF-γ and interleukin -10 (IL-10)(Th1 and Th2 pattern) to assess its relationship to the course of the disease. This paper shows that both Th1 (Il-2) and Th2 (If-γ) pathways represented by those two cytokines are not involved (Il-10 before 2,29±5,23 and after treatment 3,77±8,44; IF γ before 0,50±0,24 and after treatment 0,35±0,19). No relationship to the response to treatment was found. GC resulted in positive response in 8/22 patients, OI (12 patients) given after CS therapy, resulted in a response in all patients. Increase in proptosis, loss of visual acuity is spite of CS treatment prompted OD in two patients, who both recovered visual acuity and proptosis fell under 25mm Hertel. PMID:18039196

No changes in serum concentrations of interleukin 10 (IL-10) and interferon gamma (IF-gamma) before and after treatment of the thyroid eye disease (TED).

Science.gov (United States)

Laban-Guceva, Nevenka; Antova, Magdalena; Bogoev, Milco

2007-11-01

TED is a severe eye disease leading in rare cases to decrease of sight, optic nerve compression and blindness. Recently, significant progresses in understanding the disease have been done. Nevertheless, the treatment of the disease, especially in its severe form remains challenging. Glucocorticoids (GC) have been the basis of the treatment for a long time. Orbital irradiation (OI) and optical decompression (OD) are also used in managing the severe forms of TED. Somatostatin, intravenous immunoglobulin have been also used, with conflicting results. Regarding the potential for the treatment of TED with cytokine antagonists, controlled clinical studies are not available. Since cytokines play an important role in the pathogenesis of the TED, they seemed to be logical choice for modern TED treatment. It has been shown that both Th1 (interleukin-2, tumor necrosis factor gamma, interleukin gamma) and Th2 (interleukin -4, -5, -10) profile T cells are activated in the TED. We therefore measured interleukin-gamma, IF-gamma and interleukin -10 (IL-10)(Th1 and Th2 pattern) to assess its relationship to the course of the disease. This paper shows that both Th1 (IL-2) and Th2 (IF-gamma) pathways represented by those two cytokines are not involved (IL-10 before 2.29+/-5.23 and after treatment 3.77+/-8.44; IF gamma before 0.50+/-0.24 and after treatment 0.35+/-0.19). No relationship to the response to treatment was found. GC resulted in positive response in 8/22 patients, OI (12 patients) given after CS therapy, resulted in a response in all patients. Increase in proptosis, loss of visual acuity is spite of CS treatment prompted OD in two patients, who both recovered visual acuity and proptosis fell under 25 mm Hertel.

No Changes in Serum Concentrations of Interleukin 10 (IL-10 and Interferon γ (IF-γ Before and After Treatment of the Thyroid Eye Disease (TED

Directory of Open Access Journals (Sweden)

Nevenka Laban-Gučeva

2008-11-01

Full Text Available TED is a severe eye disease leading in rare cases to decrease of sight, optic nerve compression and blindness. Recently, significant progresses in understanding the disease have been done. Nevertheless, the treatment of the disease, especially in its severe form remains challenging. Glucocorticoids (GC have been the basis of the treatment for a long time. Orbital irradiation (OI and optical decompression (OD are also used in managing the severe forms of TED. Somatostatin, intravenous immunoglobulin have been also used, with conflicting results. Regarding the potential for the treatment of TED with cytokine antagonists, controlled clinical studies are not available. Since cytokines play an important role in the pathogenesis of the TED, they seemed to be logical choice for modern TED treatment. It has been shown that both Th1 (interleukin-2, tumor necrosis factor γ, interleukin γ and Th2 (interleukin-4,-5-,-10 profile T cells are activated in the TED. We therefore measured interleukin-γ, IF-γ and interleukin -10 (IL-10(Th1 and Th2 pattern to assess its relationship to the course of the disease. This paper shows that both Th1 (Il-2 and Th2 (If-γ pathways represented by those two cytokines are not involved (Il-10 before 2,29±5,23 and after treatment 3,77±8,44; IF γ before 0,50±0,24 and after treatment 0,35±0,19. No relationship to the response to treatment was found. GC resulted in positive response in 8/22 patients, OI (12 patients given after CS therapy, resulted in a response in all patients. Increase in proptosis, loss of visual acuity is spite of CS treatment prompted OD in two patients, who both recovered visual acuity and proptosis fell under 25mm Hertel.

Clinical significance of changes of serum contents of IL-8, CT, BGF and T in elderly men with osteoporosis