WorldWideScience

Sample records for sovrapressione il metodo

  1. Stima dell’effetto delle esternalità localizzative sui valori immobiliari tramite il metodo Delphi

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    Boaz Barzilay

    2012-12-01

    Full Text Available Il metodo Delphi è un metodo per raccogliere e strutturare indicazioni provenienti da un gruppo di esperti, utilizzando un questionario combinato con un feedback controllato delle opinioni. Il presente contributo esamina i principi fondamentali del metodo Delphi e tenta di convalidare i suoi risultati, utilizzando dati ottenuti mediante le normali tecniche econometriche di valutazione immobiliare, come, ad esempio, il metodo del prezzo edonico. Il metodo Delphi, come sosteniamo, può diventare uno strumento utile per la valutazione immobiliare in casi particolari, come i piccoli comuni con vendite di abitazioni relativamente scarse ed economie di transizione caratterizzate da mercati immobiliari in via di sviluppo.

  2. La scrittura è terapeutica? Il metodo autobiografico e la composizione del sé

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    Nicola Ghezzani

    2010-02-01

    Full Text Available Far da sé il proprio ritratto biografico significa, in rapporto a queste alienazioni, sfidare i demoni della compiacenza e della connivenza con l’altro, quindi porre il rifiuto, l’opposizione e quindi il vuoto, il nulla, l’assenza come base sulla quale veder apparire le proprie scene e le proprie passioni. Solo se non devo rispondere di me stesso a nessun altro che a me stesso, io sono nella condizione di cogliermi nella mia delusione fondamentale, nell’opposizione frontale che ho verso il mondo o verso i valori recepiti, nella mia protesta di riscatto dalla soggezione, nelle mie istanze di vendetta, di cui avverto insieme la violenza apocalittica e la colpa morale, quindi posso valutare quanto sono trascinato da passioni, reso nemico agli altri e a me stesso, e quanto posso riequilibrare il mio essere sulla base di una valutazione intima, sentita, ponderata di ogni lato contrapposto della mia identità.

  3. Action Research in the Library: Method, Experiences, and a Significant Case La ricerca-azione in biblioteca: il metodo, le esperienze e un caso significativo

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    Ilaria Moroni

    2011-12-01

    Full Text Available This article aims to promoting action research in library contexts by illustrating the method and its applications in library, and by presenting a meaningful case.
    Action research, devised in 1950s, was spread in information sciences since 1990s, with results that have been interesting in promoting change of involved people and organizations. The method is based on engaging a group coordinated by a researcher. Problem analysis is functional to realizing improvement interventions, in a recursive process of reflection, action, evaluation, and result sharing.
    The action research case at the University Milano Bicocca Library is meaningful under various aspects: increase of motivation and awareness in the working group that was responsible of improving the perception of library services; complementary use of quantitative and qualitative research methods in order to analyze users' service utilization and satisfaction; realization of many interventions, coherent with research results, aimed to enhance service usage and perceived quality; self-reflection and reflection on the organizational context, benchmarking with other libraries and assessment of the realized activities in the perspective of continuing improvement; internal sharing and external diffusion of the project to the advantage of librarians, users, and researchers.

    L’articolo si propone di diffondere l’utilizzo della ricerca-azione nel contesto bibliotecario, illustrando il metodo e le sue applicazioni nelle biblioteche e presentando un caso significativo.

    La ricerca-azione, ideata negli anni Cinquanta, si è diffusa nell’ambito delle scienze dell’informazione a partire dagli anni Novanta con risultati interessanti per i cambiamenti promossi nelle persone e nelle organizzazioni coinvolte. Il metodo prevede il coinvolgimento di un gruppo di persone coordinate da un ricercatore e l’analisi del problema è funzionale alla realizzazione di interventi migliorativi, in

  4. L’INFLUENZA DELLE DIFFERENZE CULTURALI NELL’APPRENDIMENTO DELL’ITALIANO L2 DA PARTE DEGLI APPRENDENTI SINOFONI: IL METODO DI STUDIO E L’INSEGNAMENTO DELLA LINGUA STRANIERA IN CINA

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    Gilda Consalvo

    2012-07-01

    Full Text Available Spesso la grande differenza tra la cultura italiana e quella cinese rende il percorso di apprendimento del discente sinofono particolarmente lento e difficile. Come dimostrato da diversi studi, infatti, la cultura di appartenenza ricopre un ruolo fondamentale nell’apprendimento linguistico.Il presente articolo, dopo una breve comparazione tra le peculiarità delle due culture in questione secondo le categorie di Geert Hofstede (1991, illustra il metodo di insegnamento utilizzato nelle suole cinesi, il ruolo dell’insegnante all’interno della classe e della società, il rapporto tra insegnante e studente, approfondendo in modo particolare lo stile di apprendimento dei discenti sinofoni e le loro strategie messe in atto per apprendere la lingua straniera.Lo scopo è fornire informazioni che consentano di comprendere cosa accade quando i discenti sinofoni si trovano in una classe di lingua straniera o seconda con insegnanti madrelingua di culture così differenti e in un contesto di apprendimento diverso da quello già sperimentato nel loro paese e di poter rispondere alle loro esigenze con un intervento didattico adeguato.THE INFLUENCE OF CULTURAL DIFFERENCES IN ITALIAN L2 LEARNING BY CHINESE-SPEAKERS: METHOD OF STUDY AND FOREIGN LANGUAGE TEACHING IN CHINAOften the huge difference between Italian and Chinese cultures makes the learning process for Chinese-speaking students particularly hard and slow. As many studies have shown, in fact, the home culture plays a fundamental role in language learning.This article, after a brief comparison between the two cultures according to the categories defined by Geert Hofstede (1991, illustrates teaching methods used in Chinese schools, the teacher’s role in the classroom and in society and the relationship between teacher and student, investigating the learning style of Chinese-speaking students and the strategies they implement when learning a foreign language.The aim is to offer information which

  5. Stime della biomassa marina attraverso il metodo acustico: discernimento delle specie e gestione delle risorse ittiche - Acoustical estimation of fish biomass: species identification and stocks management

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    Víctor Espinosa

    2015-09-01

    Full Text Available L’acustica è alla base delle più importanti tecnologie nelle telecomunicazioni subacquee, nonché nel rilevamento e nella determinazione dei target acustici nei mezzi acquatici. Le misure a multi-frequenza sono lo strumento principale per l’identificazione selettiva delle specie marine e per la pesca sostenibile. Lo sviluppo di sistemi a larga banda larga e le tecniche basate su sonar multi-beam costituiscono l'attuale sfida per gli scienziati e gli sviluppatori. Al contempo, sistemi più semplici ed economicamente efficienti, come boe satellitari, sono in grado di offrire informazioni per il monitoraggio degli ecosistemi o l’individuazione di specie bersaglio nella pesca marittima. ------ Acoustics is the basics of the most important technologies for underwater telecommunication, as well as for target detection and identification in the aquatic media. Multiple frequency measurements are the key for species discrimination and open the door for sustainable fisheries. The development of wider broadband systems and quantitative multi-beam sonars and processing techniques constitute the present challenge for scientists and developers. In parallel, simpler and cost-efficient systems like satellite buoys can offer clue information for marine ecosystem monitoring or target species fisheries.

  6. LE «SOTTIGLIEZZE DI CERTA DIDATTICA SUPERLATIVA» DELLA GRAMMATICA ELEMENTARE: STORIA (ATTESTATA DEL METODO RAFFORZISTA (1814-1914

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    Michela Dota

    2018-03-01

    Full Text Available Il contributo ripercorre la storia e le peculiarità del metodo rafforzista, metodo glottodidattico per l’insegnamento della lettura e della scrittura. Il metodo, nato in Italia nel primo Ottocento, nell’epoca postunitaria era praticato nelle scuole elementari soprattutto dell’Italia meridionale, nonché nelle scuole reggimentali e in alcuni istituti per sordomuti. Le sue fondamenta, aberranti rispetto alla norma ortografica e ortoepica tradizionale, lo resero obiettivo di un tenace ostracismo da parte del Ministero dell’Istruzione pubblica, sostenuto per questa occasione da due tra i più eminenti glottologi dell’epoca: Graziadio Isaia Ascoli e Francesco Lorenzo Pullè. Il metodo finì per estinguersi nel secondo decennio del Novecento.   The history of the “metodo rafforzista” for teaching Italian (1814-1914 This article retraces the history and peculiarities of the “metodo rafforzista”, a language teaching method developed in Italy during the first part of 1800s. In the post-Unitarian period, it was used in elementary schools, especially in Southern Italy, and also in military schools and in some institutes for the Deaf and Dumb. Orthographic and orthoepic models proposed by the “metodo rafforzista” diverged from rules of traditional Italian grammar. The method, supported by Graziadio Isaia Ascoli and Francesco Lorenzo Pullè, two of the most distinguished Italian linguists at that time, was subsequently rejected by the Ministry of Public Education, and it vanished during the second half of 1900s.

  7. GIUSEPPE DE ROSA, Metodo per pianisti accompagnatori della danza, Milano, Suvini Zerboni, 2010

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    Chiara Sintoni

    2014-12-01

    Full Text Available Il volume di Giuseppe De Rosa è al contempo un agile metodo teorico-pratico per la formazione del pianista accompagnatore della danza classica e un sussidio didattico per la sua attività in situazione. Frutto dell’esperienza pluriennale dell’autore, colma un vuoto nella pubblicistica italiana dedicata all’argomento.

  8. ALLA SCOPERTA DEL PACKAGING DESIGN CON IL WEBQUEST

    OpenAIRE

    Gobbis, Antonietta; Paoli Legler, Marco

    2013-01-01

    Il seguente saggio tratta le possibilità di presentazione in Università straniere, dove si insegna l’ItalianoL2, di un aspetto culturale italiano di forte impatto all’estero come il design, attraverso l’innovativa metodologia del webquest. L’iniziale parte teorica descrive il webquest come metodo didattico costruttivista, con particolare riferimento alle sue caratteristiche, parti costituenti e tipologie. Nella seconda parte vengono dati esempi concreti di webquest di breve e lunga durata su ...

  9. Subsurface microbial ecology. Epi fluorescence direct counts; Ecologia microbica del sottosuolo: metodo di conta diretta in epifluorescenza

    Energy Technology Data Exchange (ETDEWEB)

    Barra Caracciolo, A.; Silvestri, C.; Creo, C.; Izzo, G. [ENEA, Centro Ricerche Casaccia, Rome (Italy). Dipt. Ambiente

    1998-07-01

    To the aim of recognize the importance of microorganisms in affecting or even determining the fate of xenobiotics in the subsurface environment evaluating bacteria concentration in a subsurface ecosystem, the report discusses a soil sample treatment method which has been developed for epi fluorescence direct counting with DAPI. [Italian] Lo studio discute un metodo di trattamento del campione per la conta diretta in epifluorescenza con un marcatore selettivo per il DNA, il DAPI, al fine di quantificare la concentrazione batterica del sottosuolo e studiare il ruolo dei microrganismi nella biodegradazione delle molecole esogene, ancora poco indagato.

  10. Il metodo della fisica e le problematiche della biologia

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    Tripodi, G

    2007-07-01

    Full Text Available Following the ancient Hermetic aphorism solve et coagula, we investigate the nature of the interface between physics and biology by moving up and down the different temporal and spatial scales which enter the description of natural phenomena. Various indications seem to support both the existence of such an interface and the possibility of finding methods, languages, and targets shared by such two disciplines. However, this possibility becomes remote if one moves further and further from the microscopic level of atoms and molecules (and, correspondingly, of molecular biology. We conclude that the biologically founded epistemology proposed by Maturana and Varela as well as cultural anthropology and sociology cannot yet be treated with the methodology of physics.

  11. Vico e il problema del metodo tra sperimentalismo e retorica

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    Giulio Gisondi

    2016-12-01

    Full Text Available [Vico and the Problem of Method between Rhetoric and Experimentalism]. This paper analyses some of the major issues discussed by Vico in his De nostri temporis studiorum ratione. Focusing especially on books VII and X, the author examines Vico’s comparison between the method of the “ancients” – or “topica”– and the one of the “moderns” – or critica. In this perspective, the study retraces the question of method exposed by Vico, starting from the discussions within the Accademia of Investiganti and from the heritage of humanistic rhetoric. The solution proposed by Vico to the problem of education and learning showshow it ispossible to conciliate the “ratio critica” and the “ratiotopica”. The study underlines how Vico can recovery the rhetorical method of “topica” in the context of the Cartesian debate in Naples.

  12. Il metodo di Aristarco à solo un modello?

    Science.gov (United States)

    Sigismondi, Costantino; Agolini, Giorgia

    2017-06-01

    The method of Aristarchus of Samo to measure the distance Earth-Sun is well known as the first step in the cosmological distance ladder. Our task is to understand if it is worth to repeat it also experimentally, with positive conclusions, especially with respect to the experimental design.

  13. Lingua per se notata. Una annotazione sul metodo Ørberg alla luce dell’Ipotesi del Noticing di Schmidt

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    Marco Ricucci

    2017-10-01

    Full Text Available L’istruzione classica sta attraversando una crisi mondiale per molteplici motivi:, mentre il greco antico e il latino sono stati eliminati dalle scuole superiori, persino in Italia. Questo articolo è un breve esame in cui la modalità di apprendimento della grammatica nel metodo induttivo-contestuale, approntato da Hans Ørberg, viene analizzata alla luce dell’ Ipotesi del Noticing di Richard Schmidt, linguista applicato statunitense: essa è una teoria cognitiva che spiega l’acquisizione di una lingua seconda.

  14. Spores of anaerobic clostridia for a quantitative chemical analysis methodology; Metodo per la determinazione delle spore di clostridi solfito-riduttori in campioni di sedimenti, fanghi di depurazione, suolo e prodotti di compostaggio

    Energy Technology Data Exchange (ETDEWEB)

    Bonadonna, L.; Marini, R. [Istituto Superiore di Sanita' , Rome (Italy)

    2001-02-01

    The described analytical procedure allows the quantitative enumeration of the parameter Spores of Anaerobic Clostridia in solid matrixes, such as sediment, sludge, soil and compost. The present technique should be an useful reference method for all the laboratories working on the hygienic quality control of the environment. [Italian] Viene descritto il metodo analitico per la determinazione quantitativa delle Spore di Clostridi solfito-riduttori. Il parametro viene generalmente ancora quantificato con metodiche piu' adatte per l'analisi delle acque. Il metodo qui riportato, modifica invece la procedura di rilevamento per adeguarla all'analisi di materiale solido, quali sedimento, fango di depurazione, suolo e prodotti di compostaggio e vuole essere uno strumento applicativo di riferimento utile alla pianificazione e all'unificazione delle procedure analitiche per le strutture che operano nel settore del controllo della qualita' igienico-sanitaria ed ambientale di specifiche matrici ambientali.

  15. ARTE E FENOMENOLOGIA BRANCUSIANA: “IL METODO PURAMENTE SCULTORIO DI PENSARE IL MONDO”

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    MANUELA TEODORA BALAŞCA-MIHOCI

    2010-11-01

    Full Text Available The entailing creative labour reveals works that imply the whole human thinking and sensitivity aiming to comprehend them. Thus, we can reach the great Brancusian art in understanding that, beyond the glance and the material, we find the spiritual; the last is not something untouchable, but it is a sort of co-partner of the creative life experience. Fear, love, pain, happiness, and ecstazy, all the human affinities and the substance of beingness are created by art and by philosophy alike. Merely their expression is different as concerning the material and the word. We find sameness between the capacity of communication using and feeling life through wood or rock, for example, on one hand; and the gift of putting in act and writing words, of interpreting verse, on the other. Such a similarity belongs to the unique creative agent, finally, that is varying only by the material and the expressive shape.

  16. Il laser

    CERN Document Server

    Smith, William V

    1974-01-01

    Verso il 1960, il laser era ancora "una soluzione alla ricerca di un problema", ma fin dagli anni immediatamente successivi si è rivelato uno strumento insostituibile per le applicazioni più svariate.

  17. An analytical method for determination of mercury by cold vapor atomic absorption spectroscopy; Determinazione di mercurio. Metodo per spettrometria di assorbimento atomico a vapori freddi (CV-AAS)

    Energy Technology Data Exchange (ETDEWEB)

    Campanella, L. [Rome Univ. La Sapienza, Rome (Italy); Mastroianni, D.; Capri, S.; Pettine, M. [CNR, Rome (Italy). Ist. di Ricerca sulle Acque; Spezia, S.; Bettinelli, M. [ENEL, Unified Modelling Language, Piacenza (Italy)

    1999-09-01

    An analytical procedure for the determination of total mercury in wastewaters and natural waters is described. Aqueous samples are fast digested with nitric acid by using the microwave-oven technique; the analysis of mercury is then performed by cold vapor atomic absorption spectrometry (CV-AAS) using two possible instrumental apparatus (batch system or flow injection). Sodium borohydride is used as the reducing agent for mercury in solution (Method A). The use of amalgamation traps on gold for the preconcentration of mercury lowers the detection limit of the analyte (Method B). [Italian] Viene descritta una procedura analitica per la determinazione del mercurio totale in acque di scarico e naturali. Il campione acquoso viene sottoposto a mineralizzazione con acido nitrico in forno a microonde e analizzato mediante spettroscopia di assorbimento atomico a vapori freddi (CV-AAS) in due possibili configurazioni strumentali (sistema batch oppure flow injection), utilizzando sodio boro idruro come agente riducente del mercurio (metodo A). L'impiego della trappola di oro per la preconcentrazione del mercurio mediante amalgama consente di determinare l'analita a livelli di pochi ng/L (metodo B).

  18. Peripezie di immagini: il metodo-Warburg e la Divina Commedia

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    Gioachino Chiarini

    2012-05-01

    Full Text Available The paper is part of a ‘work in progress’ on the influence of oriental cultures and religions on Western ancient literature (The Seven Gates. After a short history of use and symbolic role of the “planetary ladder” from Sumerians to Islamic literatures and cultures via Greece, Rome and Jewish mysticism, the essai tries to show that the early Christians writers preferred to avoid employing the planetary ladder as a cipher of an itinerary to God. It was only Dante, in his Divina Commedia, who resumed to use with high perfection the planetary ladder: he re-elaboreted the circular Islamic hell in the Inferno, the Islamic heaven in the Paradiso and the Islamic paradise in the Purgatorio (his source was the Latin translation of The book of the ladder of Mahomet.

  19. Problemi e di Fisica e Astronomia ed il metodo di Gerberto docente

    Science.gov (United States)

    Sigismondi, Costantino

    2015-04-01

    Teaching Physics and Astronomy to pupils of 14-19 years old requires nowadays a continuous upgrade of knowledge as well as a capacity of selecting topics. The art of presenting arguments made Gerbert the teacher Rogatus a Pluribus in the end of X century and it is still actual; the proposed series of problems wants to link everyday experiences with the mathematical models of the phenomena, to allow the prediction and explanation of the experimental data. These problems of Physics and Astronomy are “observation oriented”, as the method of Gerbert was to start from the experience to get the theory, and not viceversa. Physics is much more than an “applied Algebra”. In the dispute of Ravenna (980) between Gerbert and Otric from Magdeburg, the primacy of Physics with respect to Mathematics was discussed. In the Italian secondary technical schools there are laboratory activities, while there is nothing similar for Lyceums and for the Astronomy teaching which is limited to a series of notions to be learned without any kind of observation; considered too difficult in polluted skyes.

  20. Investigando il suono dei cieli: tra metodo scientifico e pensiero magico-simbolico

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    Stefano A.E. Leoni

    2012-11-01

    Full Text Available In the sixteenth and seventeenth centuries European scholars of natural philosophy often attempted to formalize music in apparently very different contexts. It is fascinating to follow the influence of magic and the symbolic on high culture, often resulting in controversies, and the fruitful critical reflections about the method of scientific inquiry. It is in this context that musicology becomes important, starting from the interdisciplinary musical treatises which were fashionable until the end of the seventeenth century. With regard to this specific issue, one can focus on points that link the history of scientific thought and the history of world-views to the field of music and to the possibilities of mythopoeic speculation of music, both used as a formalization of magicsymbolic universes, and as a dismantling of methodological (and ethical rational models. This essay discusses, amongst others, Kepler, Mersenne, Fludd as writers that make extensive use of the meta-language of music to give shape to their, at times controversial, ideas.

  1. Il gradiente implicito nella verifica a fatica di giunzioni saldate sollecitate a fatica

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    R. Tovo

    2009-07-01

    Full Text Available L’incremento delle potenzialità di strumenti per la progettazione assistita (come modellatori solidi e strumenti per FEA in grado di gestire modelli molto complessi permette di ipotizzare lo sviluppo di strumenti numerici specifici per la previsione della resistenza a fatica delle giunzioni saldate. Tali strumenti potrebbero essere in grado di valutare l’influenza di geometria e carichi senza la necessità di elaborazioni successive, e spesso, del progettista (come nelle tensioni di Hot Spot. Il presente lavoro propone una metodologia di calcolo adatta alla previsione della vita a fatica di giunzioni saldate complesse. Un indice di resistenza è ottenuto innanzitutto risolvendo il problema tensionale completamente in modo numerico (agli elementi finiti. La previsione della resistenza a fatica, è calcolata facendo uso di un modello analitico basato sul gradiente implicito che assume come tensione efficace la tensione equivalente non locale derivante dalla tensione principale. Dapprima verrà tarato il metodo su prove sperimentali eseguite su giunzioni saldate a croce, successivamente il metodo verrà utilizzato per la verifica a fatica di giunzioni saldate più complesse a sviluppo tridimensionale.

  2. Uso delle tecnologie nel sostegno: il punto di vista di un gruppo di insegnanti in formazione

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    Caterina Bembich

    2015-09-01

    Full Text Available Nel presente lavoro sono descritti gli esiti di un’indagine esplorativa, che prende in esame il punto di vista di un gruppo di insegnanti in formazione, sull’uso delle TIC nella didattica rivolta a studenti con disabilità/Bisogni Educativi Speciali (BES. È stato proposto ai docenti un questionario, al termine di un percorso formativo laboratoriale sull’uso delle TIC, che aveva l’obiettivo di indagare tre dimensioni: (1 aspetti formativi (conoscenze di base possedute dagli insegnanti sulle tecnologie; competenze acquisite durante il percorso formativo; applicabilità delle competenze nel lavoro in classe; (2 efficacia percepita nell’utilizzo delle TIC per il raggiungimento di diversi obiettivi didattici; (3 difficoltà e aspetti di criticità rilevati nell’utilizzo delle TIC. Nell’articolo saranno descritti nel dettaglio il metodo, le aree indagate e i risultati principali ottenuti dall’indagine, proponendo una riflessione critica sulle tematiche emerse.

  3. Il Self, la vita e il lavoro: l'esperienza dei gruppi Isadora Duncan

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    Pietro Barbetta

    2006-12-01

    Full Text Available Dipendenze e psicosi. Servizi per le dipendenze e psichiatria. Delirium indotto da sostanze e delirio schizofrenico. Si tratta di due modi diversi di uscire dal seminato, di deragliare. Di due preoccupazioni diverse per i servizi della salute mentale. Di due concezioni diverse per affrontare le questioni filosofiche. Cartesio introduce per primo questa partizione distinguendo il sogno dalla follia, poi Nietszche riprende la questione sottolineando le differenze tra chi delira e chi il delirio se lo deve procurare. Dall’altra parte c’è il mondo della tecnologia dispiegata, dell’organizzazione socio sanitaria razionale. Chi ha analizzato questi argomenti con maggiore lucidità nella seconda metà del Novecento sono certamente autori che non hanno fatto parte, se non in modo marginale e critico, di questo mondo: Gregory Bateson, Gilles Deleuze, Michel Foucault. D’altro canto non possiamo ricondurre semplicisticamente, come a volte è stato fatto, tutta questa fenomenologia della mente moderna alla sola opera filosofica. Cartesio non basta, né forse ne è la principale fonte. Perché una mentalità fortemente improntata al metodo razionale prenda il sopravvento sono necessarie pratiche sociali che impregnano il quotidiano e che, come ha osservato Bateson, costruiscono una cibernetica del Self. In questo breve saggio si connette ciò che è accaduto nel Seicento - a partire dagli studi di Yates, Max Weber, Bercovich, Paden e lo stesso Foucault - a ciò che sta accadendo ora nell’ambito della salute mentale. Il puritanesimo, questa tecnologia del Self che guarisce e purifica, e lo psico-farmaco, come intervento chimico puritano. Si propone poi un’esperienza teatrale di recupero dei frammenti immaginari sparsi nell’orizzonte schizofrenico o affogati nei fumi dell’alcol: l’esperienza dei Gruppi Isadora Duncan.

  4. 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.

    Science.gov (United States)

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

    2015-11-01

    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. © The Author(s) 2015.

  5. Crowdfunding per il Patrimonio Culturale nei Centri Storici Minori: la Chiesa di San Michele a Savoca

    Directory of Open Access Journals (Sweden)

    Antonino Cosentino

    2016-08-01

    Full Text Available Questo articolo illustra la campagna di crowdfunding “Save the Soul of Savoca” per finanziare il restauro di un ciclo di dipinti settecenteschi nel piccolo borgo di Savoca (ME. Si presenta questa iniziativa come un modello per la salvaguardia del patrimonio culturale del nostro Paese che è vastissimo, distribuito su numerose piccole realtà locali e spesso non adeguatamente tutelato. Il finanziamento erogato dallo Stato e dagli enti locali rappresenta, ancora oggi, la fonte di sostentamento principale per le iniziative che coinvolgono il settore dei beni culturali. Tuttavia, l’attuale congiuntura economica ha favorito la nascita e la diffusione di strumenti e modalità di finanziamento alternativi attraverso i quali poter supportare il restauro del nostro Patrimonio Culturale. Il crowdfunding è il metodo che più si sta diffondendo ed è una forma di microfinanziamento dal basso finalizzato alla creazione e al supporto di un processo collaborativo tra singoli soggetti che utilizzano il proprio denaro per sostenere iniziative di singoli individui o di organizzazioni più strutturate. Molteplici sono gli esempi attuali di impiego del crowdfunding, da parte di associazioni e comitati, per il restauro di monumenti di interesse nazionale.

  6. Il mondo dentro il mondo

    CERN Document Server

    Barrow, John D

    1991-01-01

    Davvero esistono “lì fuori” leggi di natura, che stanno in attesa di essere scoperte, indipendenti dal nostro modo di pensare, o esse rappresentano soltanto la descrizione più conveniente di ciò che abbiamo visto? Come è nata l’idea stessa di “leggi di natura”? Queste costituiscono la realtà profonda o sono soltanto pezzi di un regolamento che ci siamo dati per organizzare meglio la nostra conoscenza del mondo? o semplici paletti che piantiamo e ci lasciamo alle spalle come segnali via via che procediamo nella giungla dell’esperienza? È possibile che non esistano affatto leggi di natura? Forse esse, e anche l’universo che da esse sembra regolato, sono del tutto creazioni della nostra mente: un’illusione che scompare appena cessiamo di pensarvi. Ma allora, che cosa accadrebbe, se non ci fossero osservatori dell’universo?». Interrogativi di questo genere, che incontriamo sulla soglia del Mondo dentro il mondo, sarebbero suonati eccentrici fino a qualche anno fa. Oggi, al contrario, circ...

  7. ALLA SCOPERTA DEL PACKAGING DESIGN CON IL WEBQUEST

    Directory of Open Access Journals (Sweden)

    Antonietta Gobbis

    2013-01-01

    Full Text Available Il seguente saggio tratta le possibilità di presentazione in Università straniere, dove si insegna l’ItalianoL2, di un aspetto culturale italiano di forte impatto all’estero come il design, attraverso l’innovativa metodologia del webquest. L’iniziale parte teorica descrive il webquest come metodo didattico costruttivista, con particolare riferimento alle sue caratteristiche, parti costituenti e tipologie. Nella seconda parte vengono dati esempi concreti di webquest di breve e lunga durata su due prodotti italiani molto famosi di packaging design, che hanno festeggiato il loro anniversario nel 2012: il Bacio Perugina e il Campari Soda. I risultati positivi di entrambi i progetti intendono mostrare i vantaggi di una didattica centrata sull’alunno basata su attività di problem-solving e strategie di cooperative learning.  Discovering packaging design through webquest The following essay deals about the possibilities to introduce a very successful cultural topic like Italian Design in Universities abroad, where Italian is taught as second foreign language, through the innovative methodology of WebQuests. The theoretical part describes WebQuests as constructivist didactic method with reference to its characteristics, main constituent parts  and typologies. In the second part we give concrete examples of short and long term WebQuests about two very famous packaging design Italian products which celebrated in 2012 their anniversary: BacioPerugina and Campari Soda. The positive results of both projects aim to show the advantages of learner-centered teaching methods based on problem-solving activities and cooperative learning strategies.

  8. Il secondo principio

    CERN Document Server

    Atkins, Peter W

    1988-01-01

    L'asimmetria della Natura ; l'indicatore di una trasformazione ; scivolando verso il caos ; la quantificazione del caos ; la potenzialità del caos ; le trasformazioni del caos ; il dominio della temperatura ; caos costtrutivo ; le strutture del caos.

  9. Evaluation of IL-2, IL-6, IL-8 and IL-10 in Malignant Melanoma Diagnostics.

    Science.gov (United States)

    Kucera, Radek; Topolcan, Ondrej; Treskova, Inka; Kinkorova, Judita; Windrichova, Jindra; Fuchsova, Radka; Svobodova, Sarka; Treska, Vladislav; Babuska, Vaclav; Novak, Jaroslav; Smejkal, Jiri

    2015-06-01

    The aim of the present study was to evaluate the usefulness of four interleukins (IL-2, IL-6, IL-8 and IL-10) for melanoma detection and correlate these interleukins with sentinel node metastasis positivity. A group of 236 persons was assessed: 175 patients with melanomas and 61 healthy persons. Melanoma patients were divided to four groups according to Breslow score. We determined IL-2, IL-6, IL-8 and IL-10 in each plasma sample. Interleukin plasma levels were assayed using a Human Cytokine Milliplex Map kit. Measurements were performed using the Bio-Plex MAGPIX Multiplex Reader. Plasma samples were collected prior to surgery or any other form of treatment. All melanoma diagnoses were histologically verified. We compared interleukin plasma levels in the healthy group and plasma levels in each Breslow score stage. In the first Breslow score stage, IL-2 (pmelanoma. IL-2 and IL-6 appear to be prognostic biomarkers. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  10. DOLOČITEV POVRŠINSKE NAPETOSTI Z METODO KAPILARNEGA DVIGA DVOFAZNIH SISTEMOV

    OpenAIRE

    Kravanja, Gregor

    2014-01-01

    Namen magistrske naloge je bil postavitev merilne naprave in razvoj nove metode merjenja površinske napetosti s kapilarnim dvigom dvofaznih sistemov v okolici kritične točke. Za pridobitev natančnih in primerljivih meritev je bilo potrebno poznati natančni notranji premer tankih kapilar. Določili smo ga z metodo laserskega tipanja na nemški koordinatni merilni napravi ZEISS tipa UMC-850 s pomočjo merilne programske opreme CALYPSO 5.1.4. Za merjenje ravnotežne višine smo uporabili računalniški...

  11. Il muro come galleria

    Directory of Open Access Journals (Sweden)

    Duccio Dogheria

    2008-06-01

    Full Text Available Il muro, nel suo grigio rigore formale, nella sua fredda geometria, nel suo intento divisorio, nasconde spesso il cielo. Sovente il linguaggio dell’arte, ma non di meno quello della comunicazione, hanno interferito con le sue algide barriere. In molti casi, beninteso, non è che il potere in altre forme, che interferisce con se stesso: pensiamo ai bandi affissi agli angoli delle città, o le lettere d’indulgenza papali -spesso impreziosite da miniature al punto da poterle considerare antenate dal manifesto- che nel corso del medioevo venivano affisse sulle porte delle chiese.

  12. Raised IL-6 Levels

    African Journals Online (AJOL)

    user

    ABSTRACT. Objectives: The objectives of the study were to compare plasma levels of IL-6 in HIV positive and. HIV negative individuals and to correlate them with. CD4 count. Materials and methods: A cross-sectional study was carried out at the University Teaching Hospital in Lusaka, Zambia. IL-6 and CD4 were assessed ...

  13. Il teatro degli spiriti.

    OpenAIRE

    Chiara Pussetti

    2013-01-01

    Questo saggio è dedicato a un culto di possessione, in cui tutte ledonne, investite dagli spiriti degli uomini morti prima dell’iniziazione, compiono un percorso iniziatico parallelo a quello maschile, consentendo a queste anime, potenzialmente pericolose, di completare il cammino che non hanno potuto percorrere da vivi e quindi di raggiungere serenamente il mondo dei morti, come antenati protettori del villaggio

  14. Marketing; Il marketing

    Energy Technology Data Exchange (ETDEWEB)

    Muscigna, M. [ENEA, Centro Ricerche Casaccia, S. Maria di Galeria, RM (Italy). Dipt. Innovazione

    1999-07-01

    The report discusses marketing strategies oriented to the organizations and analyzes its critical factors, which determine the success of the organization activity. [Italian] Il rapporto analizza i caratteri delle strategie del marketing orientato all'impresa. Vengono infine analizzati i fattori critici che determinano il successo o l'insuccesso delle scelte aziendali.

  15. Il Bosone di Higgs

    CERN Multimedia

    Hemmer, Sabine

    2018-01-01

    Poster di ATLAS sul bosone di Higgs indirizzato al pubblico generico, che spiega il meccanismo di Brout-Englert-Higgs e la sua importanza. Spiega anche il ruolo del Bosone di Higgs, come viene cercato, il percorso della sua scoperta e cosa viene dopo la scoperta. Disponibile anche in Francese (http://cds.cern.ch/record/1697501) e Inglese (http://cds.cern.ch/record/1697389). Non esitate a utilizzarlo nelle sedi dei vostri Istituti e negli eventi divulgativi! Il poster è in formato A0. Cliccate sull'immagine per scaricare il .pdf ad alta qualità e stamparlo dove preferite. Per qualisasi domanda o commento potete contattare atlas-outreach-coordination@cern.ch

  16. Correlacion entre metodos de analisis de Zn disponible en cuatro ordenes de suelos de Costa Rica

    Directory of Open Access Journals (Sweden)

    Eloy Molina

    2001-01-01

    Full Text Available Se realizo una comparación entre métodos analisis del Zn disponible en 4 ordenes de sue- Analytilos de Costa Rica (Ultisoles, Vertisoles, Andisoles Inceptisoles, 25 de c/u, utilizando las siguientes soluciones extractoras: Olsen Modificado, Meh- lich 3, Morgan Modificado, DTPA y HC1. Las cantidades de Zn extrafdas dependieron de la natu- raleza qufmica de la solucion extractora. El HCl presento los contenidos mas altos de Zn en los chasuelos, excepto en Vertisoles. Las soluciones que hicontienen el agente quelante EDTA (Olsen Modi- ficado y Mehlich`3, extrajeron niveles interme- Modidios de Zn, en tanto que los metodos que contie- Den el quelato DTPA (Morgan Modificado y DT - PA, obtuvieron los valores mas bajos. Las corre- laciones de Zn extrafble entre los 5 metodos fue- signifirOD significativas en la mayona de los casos, tanto nivel de orden de suelos como en el conjunto de indivilos 100 suelos analizados. Los coeficientes de co- rrelacion mas altos, se presentaron entre Mehlich Morgan Modificado y DTPA. Las correlaciones Modifueron consistentes en los 4 ordenes, 10 que indica que estas soluciones poseen un amplio margen de adaptacion a diferentes tipos de suelo, siendo una caractenstica ventajosa para la selección de un metodo de analisis. El Olsen Modificado fue mas slighteficiente para la extraccion de Zn en suelos de pH ligeramente acido 0 neutro (Vertisoles e Inceptiso- les, que en suelos acidos (Ultisoles y Andisoles. EI HCI extrajo cantidades muy aItas de Zn que Moraparentementestan relacionadas con formas no disponibles para lag plantas. Se concluye que lag soluciones Mehlich 3, Morgan Modificado y DT - PA son semejantes en la forma de extraer Zn dispo- Dible, y podrian seT una altemativa para sustituir el metoda tradicional de Olsen Modificado utilizado en Costa Rica. Sin embargo,la eficiencia de ellas no puede seT establecida sino a traves de log estudios de correlacion contra rendimiento en invernadero y campo.

  17. Il colore delle cose

    Directory of Open Access Journals (Sweden)

    Vincenzo Vitiello

    2017-09-01

    Full Text Available Tema di questo saggio è l’operare della riflessione. Vitiello, dopo essersi soffermato sulla «frattura» tra la riflessione (il «vedersi» e il suo operare in Valéry, si concentra sul processo, descritto da Hegel nella Fenomenologia dello spirito, dell’esperienza della coscienza che s’eleva a coscienza dell’esperienza. La conclusione è fortemente critica: Hegel fallisce la mèta nel punto stesso in cui la raggiunge. Infatti nel sapere assoluto, nella visione compiuta, perfetta di sé, della luce che vede luce, viene meno proprio l’esperienza della coscienza, il suo divenire, la sua «imperfezione». La critica a Hegel, passando attraverso Nietzsche, si amplia a critica del linguaggio, in particolare del linguaggio dell’«essere» e  dell’«è», e delle tautologie heideggeriane quali «das Ereignis ereignet», «das Ding dingt», «die Welt weltet». Un importante passaggio del testo è quello sul linguaggio teatrale in cui la parola sembra riacquistare il legame originale tra la voce e il gesto, che tuttavia restano divisi, perché proprio il medio che li lega, il «colore» della parola, è «fuori» della parola e del gesto. Resta la parola dell’agire, dei pragmata, in cui il fare si espone nella sua modalità più propria: nell’immediatezza del patire: il grido di dolore; o nella mediatezza riflessiva dell’imperativo morale: Handle! I due opposti «colori» delle cose.

  18. Il ponte e Heidegger

    Directory of Open Access Journals (Sweden)

    Pierluigi Giordani

    2012-08-01

    Full Text Available Le considerazioni svolte in questa nota sono un modesto sommario rispetto alle opportunità offerte dal celebre scritto di Martin Heidegger “Costruire, abitare, pensare”. In quelle pagine il ponte (tema del primo numero di “Tria” è l’intrigante simbolo preso come esempio della ”essenza” dell’abitare, intesa come “tratto fondamentale” della condizione umana (abitare come “Sein” dell’uomo.La circostanza menzionata (il contenuto del numero di “Tria” può essere quindi suggerimento e occasione per una ri-cognizione - necessariamente approssimata - del testo di Heidegger. Ricognizione resa indubbiamente più avvincente dalla possibilità di un confronto derivato dall’intervallo temporale fra il climaterio del moderno (in cui è stato redatto lo scritto di Heidegger e il presente.

  19. Il teatro degli spiriti.

    Directory of Open Access Journals (Sweden)

    Chiara Pussetti

    2013-07-01

    Full Text Available Questo saggio è dedicato a un culto di possessione, in cui tutte ledonne, investite dagli spiriti degli uomini morti prima dell’iniziazione, compiono un percorso iniziatico parallelo a quello maschile, consentendo a queste anime, potenzialmente pericolose, di completare il cammino che non hanno potuto percorrere da vivi e quindi di raggiungere serenamente il mondo dei morti, come antenati protettori del villaggio

  20. IL-9 by INFERence.

    Science.gov (United States)

    Zhou, Baohua; Kaplan, Mark H

    2013-10-17

    Despite the discovery of the cytokine over 20 years ago, the relevant biological sources of interleukin-9 (IL-9) have remained a mystery. In this issue of Immunity, Licona-Limón et al. (2013) use a newly generated reporter mouse to demonstrate a role for IL-9-secreting T cells in helminthic parasite immunity. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Assessment of the effects of IL9 , IL9R , IL17A , and IL17F gene ...

    African Journals Online (AJOL)

    Assessment of the effects of IL9 , IL9R , IL17A , and IL17F gene polymorphisms on women with allergic rhinitis in Shahrekord, Iran. ... In the gene–gene interaction analysis, we found that IL9R/IL9 genotype rs731476 T‑/rs2069885 G conferred a higher risk for AR phenotype development. We also did not find a significant ...

  2. Cytokines (interleukin-9, IL-17, IL-22, IL-25 and IL-33 and asthma

    Directory of Open Access Journals (Sweden)

    Rahim Farahani

    2014-01-01

    Full Text Available Asthma is a reversible airway obstruction that is characterized by constriction of airway smooth muscle, hyper secretion of mucus, edema and airway hyper responsiveness (AHR, mucus secretion and thickening of the basement membrane underlying the airway epithelium. During the process of airway inflammation, complex interactions of innate and adaptive immune cells as well as structural cells and their cytokines have many important roles. It was believed that airway inflammation is orchestrated by allergen specific T helper (Th 2 cells, which recruit and accumulate in the lungs and produce a range of different effector cytokines. However, more recent studies have revealed the potential collaboration of other helper T cells and their cytokines in this process. Th17 cell may have a role in severe asthma and chronic obstructive pulmonary disease (COPD. Interleukin (IL-9-producing subset called Th9 cell, Th22 cells which primarily secrete IL-22, IL-13 and tumor necrosis factor-α and Th25 cells via producing IL-25 are believed to be important for initiating allergic reactions and developing airway inflammation. Cytokines are important in asthma and play a critical role in orchestrating the allergic inflammatory response, although the precise role of each cytokine remains to be determined. The aim of this review is to summarize the current knowledge about the possible roles of newly identified helper T cells derived cytokines (IL-9, 17, 22, 25 and IL-33 in asthma. The potential therapeutic applications emerging from the roles of these cytokines will be discussed as well.

  3. 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 .

  4. Il corpo della strega

    Directory of Open Access Journals (Sweden)

    Georges Bertin

    2004-09-01

    Full Text Available Come già evidenziato a proposito di altre pratiche, il sabba, attività ludica profana, religiosa, conferiva a ciascuno la possibilità di giocare efficacemente con la dinamica di un mondo da cui emergeva una figura archetipica, la strega, principale attore di questa danza in tondo. Il sabba era, dunque, uno dei luoghi ove si cristallizzavano le figure del proibito, questo per il suo carattere sacro, per la violenza istituzionale che presiedeva alla formazione dei rapporti sociali, e conferiva anche, per le caratteristiche di protesta che rivela, un'immagine sempre esaltante della capacità delle società a resistere. Il problema della nostra epoca ove rifioriscono le streghe nelle più svariate forme è, forse, quello di riallacciarsi con la dimensione gruppale dei nostri svaghi, nelle loro differenti forme e, contemporaneamente, con perdita di energia, a quanto presiedeva ai sabba e alla loro risoluzione sacrificale. In contro-corrente ai modelli meccanici che assegnano dei limiti precisi e funzionali ai corpi asserviti ad un ideale di controllo, il corpo sabbatico con la sua enfasi sulle posizioni limite (ciò che si rimproverava d'altronde alle streghe, era veramente corpo mistico.

  5. Multiple lipopolysaccharide (LPS) injections alter interleukin 6 (IL-6), IL-7, IL-10 and IL-6 and IL-7 receptor mRNA in CNS and spleen.

    Science.gov (United States)

    Szot, Patricia; Franklin, Allyn; Figlewicz, Dianne P; Beuca, Timothy Petru; Bullock, Kristin; Hansen, Kim; Banks, William A; Raskind, Murray A; Peskind, Elaine R

    2017-07-04

    Neuroinflammation is proposed to be an important component in the development of several central nervous system (CNS) disorders including depression, Alzheimer's disease, Parkinson's disease, and traumatic brain injury. However, exactly how neuroinflammation leads to, or contributes to, these central disorders is unclear. The objective of the study was to examine and compare the expression of mRNAs for interleukin-6 (IL-6), IL-7, IL-10 and the receptors for IL-6 (IL-6R) and IL-7 (IL-7R) using in situ hybridization in discrete brain regions and in the spleen after multiple injections of 3mg/kg lipopolysaccharide (LPS), a model of neuroinflammation. In the spleen, LPS significantly elevated IL-6 mRNA expression, then IL-10 mRNA, with no effect on IL-7 or IL-7R mRNA, while significantly decreasing IL-6R mRNA expression. In the CNS, LPS administration had the greatest effect on IL-6 and IL-6R mRNA. LPS increased IL-6 mRNA expression only in non-neuronal cells throughout the brain, but significantly elevated IL-6R mRNA in neuronal populations, where observed, except the cerebellum. LPS resulted in variable effects on IL-10 mRNA, and had no effect on IL-7 or IL-7R mRNA expression. These studies indicate that LPS-induced neuroinflammation has substantial but variable effects on the regional and cellular patterns of CNS IL-6, IL-7 and IL-10, and for IL-6R and IL-7R mRNA expression. It is apparent that administration of LPS can affect non-neuronal and neuronal cells in the brain. Further research is required to determine how CNS inflammatory changes associated with IL-6, IL-10 and IL-6R could in turn contribute to the development of CNS neurological disorders. Published by Elsevier Ltd.

  6. IL web tutorials

    DEFF Research Database (Denmark)

    Hyldegård, Jette; Lund, Haakon

    2012-01-01

    The paper presents the results from a study on information literacy in a higher education (HE) context based on a larger research project evaluating 3 Norwegian IL web tutorials at 6 universities and colleges in Norway. The aim was to evaluate how the 3 web tutorials served students’ information...... seeking and writing process in an study context and to identify barriers to the employment and use of the IL web tutorials, hence to the underlying information literacy intentions by the developer. Both qualitative and quantitative methods were employed. A clear mismatch was found between intention...... and use of the web tutorials. In addition, usability only played a minor role compared to relevance. It is concluded that the positive expectations of the IL web tutorials tend to be overrated by the developers. Suggestions for further research are presented....

  7. Transit Oriented Development: una soluzione per il governo delle aree di stazione

    Directory of Open Access Journals (Sweden)

    Enrica Papa

    2008-03-01

    Full Text Available I processi di diffusione e dispersione insediativa, la crescente crisi da congestione, la disponibilità di aree libere a seguito di dismissione di impianti industriali in aree strategiche della città, i consistenti investimenti in infrastrutture di trasporto su ferro in ambito urbano e regionale sono elementi chiave che hanno contribuito alla diffusione di teorie e pratiche per uno “sviluppo urbano orientato al sistema di trasporto pubblico su ferro”: il Transit Oriented Development- TOD. Questo termine, introdotto per la prima volta da Calthorpe nel 1993, sintetizza teorie e metodi volti a favorire uno sviluppo metropolitano policentrico i cui poli sono i Transit Villages ovvero comunità urbane ad alta densità e mixitè funzionale che si sviluppano intorno alle stazioni della rete su ferro. Nelle aree in espansione o in trasformazione il TOD propone la costruzione di nuovi centri urbani di elevata qualità urbana in aree della città consolidata il TOD prevede il riempimento dei vuoti esistenti ed interventi di riqualificazione urbana. Da molti anni si stanno mettendo in pratica questi principi prevalentemente negli Stati Uniti, dove la disponibilità di suoli e la necessità di limitare fenomeni di sprawl urbano hanno favorito la diffusione delle pratiche TOD in molte città. In Europa questo tipo di interventi non è ancora molto diffuso, a meno di alcuni casi specifici. L’articolo, partendo da queste premesse, vuole contribuire ad affrontare alcune questioni centrali: in quali modo è possibile “esportare” i metodi e le tecniche del TOD nelle città Europee e in particolare in Italia? Quali sono gli strumenti e le procedure per la definizione degli interventi? A partire da uno studio della letteratura scientifica e dall’analisi di casi di studio internazionali il paper propone alcune prime risposte attraverso una proposta di metodo per l’applicazione delle pratiche TOD nelle aree metropolitane italiane.

  8. Il Fedone di Platone

    Directory of Open Access Journals (Sweden)

    Maria Chiara Pievatolo

    2015-01-01

    Full Text Available Nei colloqui precedenti si erano toccate molte opinioni filosofiche sbagliate, e allora Socrate dice: “Sarebbe ben comprensibile se uno, a motivo dell’irritazione per tante cose sbagliate, per il resto della sua vita prendesse in odio ogni discorso sull’essere e lo...

  9. Helping You Buy ILS

    Science.gov (United States)

    Cibbarelli, Pamela R.

    2010-01-01

    This article is the fourth in a series of articles published annually by "Computers in Libraries" surveying integrated library systems and services (ILSs). The purpose of the annual survey is to enable comparison of the ILSs that are available. ILS vendors are in constant pursuit of an ever-changing, consistently vague definition of what the…

  10. Il dono del racconto

    DEFF Research Database (Denmark)

    Polito, Paola

    1998-01-01

    'importanza assunta nel romanzo dal piano dell'enunciazione come luogo privilegiato di manifestazione del soggetto quale esperiente una vicenda di maturazione. Il protagonista, qui, non solo si rappresenta in ciò che enuncia e riferisce, ma anche e soprattutto si svela nelle modalità specifiche del proprio discorso...

  11. Il pericolo degli ebook

    Directory of Open Access Journals (Sweden)

    Maria Chiara Pievatolo

    2014-01-01

    Full Text Available I libri stampati: si possono acquistare anonimamente in contanti; quindi se ne è proprietari: non dobbiamo firmare una licenza che ne restringe l’uso: il loro formato è noto e per leggerli non occorrono tecnologie proprietarie; si possono dare, prestare o...

  12. IL-6/IL-12 Cytokine Receptor Shuffling of Extra- and Intracellular Domains Reveals Canonical STAT Activation via Synthetic IL-35 and IL-39 Signaling.

    Science.gov (United States)

    Floss, D M; Schönberg, M; Franke, M; Horstmeier, F C; Engelowski, E; Schneider, A; Rosenfeldt, E M; Scheller, J

    2017-11-09

    IL-35 and IL-39 are recently discovered shared members of the IL-6- and IL-12-type cytokine family with immune-suppressive capacity. IL-35 has been reported to induce the formation of four different receptor complexes: gp130:IL-12β2, gp130:gp130, IL-12β2:IL-12β2, and IL-12β2:WSX-1. IL-39 was proposed to form a gp130:IL-23R receptor complex. IL-35, but not IL-39, has been reported to activate non-conventional STAT signaling, depending on the receptor complex and target cell. Analyses of IL-35 and IL-39 are, however, hampered by the lack of biologically active recombinant IL-35 and IL-39 proteins. Therefore, we engineered chimeric cytokine receptors to accomplish synthetic IL-35 and IL- 39 signaling by shuffling the extra- and intracellular domains of IL-6/IL-12-type cytokine receptors, resulting in biological activity for all previously described IL-35 receptor complexes. Moreover, we found that the proposed IL-39 receptor complex is biologically active and discovered two additional biologically active synthetic receptor combinations, gp130/IL-12Rβ1 and IL-23R/IL-12Rβ2. Surprisingly, synthetic IL-35 activation led to more canonical STAT signaling of all receptor complexes. In summary, our receptor shuffling approach highlights an interchangeable, modular domain structure among IL-6- and IL-12-type cytokine receptors and enabled synthetic IL-35 and IL-39 signaling.

  13. Estudio numerico y experimental del proceso de soldeo MIG sobre la aleacion 6063--T5 utilizando el metodo de Taguchi

    Science.gov (United States)

    Meseguer Valdenebro, Jose Luis

    improvement on mechanical properties in aluminum metal joint. Los procesos de soldadura por arco electrico representan unas de las tecnicas mas utilizadas en los procesos de fabricacion de componentes mecanicos en la industria moderna. Los procesos de soldeo por arco se han adaptado a las necesidades actuales, haciendose un modo de fabricacion flexible y versatil. Los resultados obtenidos numericamente en el proceso de soldadura son validados experimentalmente. Los principales metodos numericos mas empleados en la actualidad son tres, metodo por diferencias finitas, metodos por elementos finitos y metodo por volumenes finitos. El metodo numerico mas empleado para el modelado de uniones soldadas, es el metodo por elementos finitos, debido a que presenta una buena adaptacion a las condiciones geometricas y de contorno ademas de que existe una diversidad de programas comerciales que utilizan el metodo por elementos finitos como base de calculo. Este trabajo de investigacion presenta un estudio experimental de una union soldada mediante el proceso MIG de la aleacion de aluminio 6063-T5. El metodo numerico se valida experimentalmente aplicando el metodo de los elementos finitos con el programa de calculo ANSYS. Los resultados experimentales obtenidos son: las curvas de enfriamiento, el tiempo critico de enfriamiento t4/3, geometria del cordon, microdurezas obtenidas en la union soldada, zona afectada termicamente y metal base, dilucion del proceso, areas criticas intersecadas entre las curvas de enfriamiento y la curva TTP. Los resultados numericos son: las curvas del ciclo termico, que representan tanto el calentamiento hasta alcanzar la temperatura maxima y un posterior enfriamiento. Se calculan el tiempo critico de enfriamiento t4/3, el rendimiento termico y se representa la geometria del cordon obtenida experimentalmente. La zona afectada termicamente se obtiene diferenciando las zonas que se encuentran a diferentes temperaturas, las areas criticas intersecadas entre las

  14. Il nucleo terrestre: il cuore magnetico della Terra

    OpenAIRE

    De Santis, A.

    2006-01-01

    Il campo magnetico terrestre è una proprietà intrinseca del nostro pianeta e di altri oggetti del sistema solare. Il Sole stesso possiede un forte campo magnetico che si inverte quasi ciclicamente ogni 10-11 anni; tale comportamento è visibile attraverso la medesima ciclicità delle macchie solari che denotano sulla superficie l’intensa attività magnetica della nostra stella. Il campo magnetico terrestre è importantissimo per la vita sulla Terra. Esso protegge il pianeta dalle p...

  15. Il libro di fisica

    CERN Document Server

    Asimov, Isaac

    1986-01-01

    Isaac Asimov, illustre studioso e brillante divulgatore scientifico, ma anche grandissimo scrittore di science fiction, ha costruito questa volta una vera e propria «biografia delle scienze fisiche». Il presente volume, che nel mondo anglosassone è diventato una «bibbia della fisica», ci introduce, in forma semplice ma rigorosa, ai segreti dei quasar e dei buchi neri, dei quark e degli acceleratori di particelle, dell'intelligenza artificiale e delle fonti di energia, sia essa quella «sporca» sia quella «pulita». Un vero, completo manuale, ma anche un «romanzo» affascinante sia per il profano sia per l'uomo di scienza.

  16. Il maxiprocesso di Palermo

    Directory of Open Access Journals (Sweden)

    A cura di Sarah Mazzenzana

    2016-04-01

    La Torre. La “Rivista” ripubblica qui alcuni stralci dell’ordinanza di rinvio a giudizio, alla quale Giovanni Falcone e Paolo Borsellino attesero, per ragioni di sicurezza, rifugiati nell’isola dell’Asinara. Viene ricostruita la realtà disvelata dai racconti di Leonardo Vitale, di Giuseppe Di Cristina e soprattutto di Tommaso Buscetta e Salvatore Contorno. Sono brani che, anche riletti oggi, mantengono una propria potenza narrativa, perfino una certa solennità. Il Maxiprocesso si sarebbe chiuso dopo alterne vicende, il 30 gennaio del 1992, con la condanna all’ergastolo in Cassazione della cosiddetta Cupola di Cosa nostra. Per la prima volta in centotrent’anni di storia nazionale i boss mafiosi avrebbero conosciuto la condanna a vita in via definitiva. Dopo pochi mesi avrebbero risposto con le stragi, uccidendo platealmente i due principali estensori dell’ordinanza.

  17. IL21R

    Science.gov (United States)

    Bolzoni, Marina; Ronchetti, Domenica; Storti, Paola; Donofrio, Gaetano; Marchica, Valentina; Costa, Federica; Agnelli, Luca; Toscani, Denise; Vescovini, Rosanna; Todoerti, Katia; Bonomini, Sabrina; Sammarelli, Gabriella; Vecchi, Andrea; Guasco, Daniela; Accardi, Fabrizio; Palma, Benedetta Dalla; Gamberi, Barbara; Ferrari, Carlo; Neri, Antonino; Aversa, Franco; Giuliani, Nicola

    2017-04-01

    Bone marrow monocytes are primarily committed to osteoclast formation. It is, however, unknown whether potential primary alterations are specifically present in bone marrow monocytes from patients with multiple myeloma, smoldering myeloma or monoclonal gammopathy of undetermined significance. We analyzed the immunophenotypic and transcriptional profiles of bone marrow CD14 + monocytes in a cohort of patients with different types of monoclonal gammopathies to identify alterations involved in myeloma-enhanced osteoclastogenesis. The number of bone marrow CD14 + CD16 + cells was higher in patients with active myeloma than in those with smoldering myeloma or monoclonal gammopathy of undetermined significance. Interestingly, sorted bone marrow CD14 + CD16 + cells from myeloma patients were more pro-osteoclastogenic than CD14 + CD16-cells in cultures ex vivo Moreover, transcriptional analysis demonstrated that bone marrow CD14 + cells from patients with multiple myeloma (but neither monoclonal gammopathy of undetermined significance nor smoldering myeloma) significantly upregulated genes involved in osteoclast formation, including IL21R IL21R mRNA over-expression by bone marrow CD14 + cells was independent of the presence of interleukin-21. Consistently, interleukin-21 production by T cells as well as levels of interleukin-21 in the bone marrow were not significantly different among monoclonal gammopathies. Thereafter, we showed that IL21R over-expression in CD14 + cells increased osteoclast formation. Consistently, interleukin-21 receptor signaling inhibition by Janex 1 suppressed osteoclast differentiation from bone marrow CD14 + cells of myeloma patients. Our results indicate that bone marrow monocytes from multiple myeloma patients show distinct features compared to those from patients with indolent monoclonal gammopathies, supporting the role of IL21R over-expression by bone marrow CD14 + cells in enhanced osteoclast formation. Copyright© Ferrata Storti Foundation.

  18. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans

    DEFF Research Database (Denmark)

    Steensberg, Adam; Fischer, Christian Philip; Keller, Charlotte

    2003-01-01

    The purpose of the present study was to test the hypothesis that a transient increase in plasma IL-6 induces an anti-inflammatory environment in humans. Therefore, young healthy volunteers received a low dose of recombinant human (rh)IL-6 or saline for 3 h. Plasma IL-6 levels during rhIL-6 infusion...... number without effects on plasma epinephrine, body temperature, mean arterial pressure, or heart rate. In conclusion, this study demonstrates that physiological concentrations of IL-6 induce an anti-inflammatory rather than an inflammatory response in humans and that IL-6, independently of TNF......-induced leukocyte trafficking....

  19. Atlas de aves: Un metodo para documentar distribucion y seguir poblaciones

    Science.gov (United States)

    Robbins, C.S.; Dowell, B.A.; Dawson, D.K.; Alvarez-Lopez, Humberto; Kattan, Gustavo; Murcia, Carolina

    1988-01-01

    Los Atlas de Aves son proyectos nacionales o regionalies para trazar en mapas la distribucion en reproduccion de cada especie de ave. Ese procedimiento se esta usando en Europa, Australia, Nueva Zelanda, Norteamerica, y partes de Africa. El tama?o de los cuadrados varia de medio grado de latitud y Iongitud hasta 5 x 5 km. El trabajo de campo de cada proyecto exige aproxlmadamente cinco a?os, pero los aficionados pueden llevar a cabo la mayor parte del trabajo. Es posible almacenar los resultados en un computador personal. Hay muchos beneficios: (I) se presenta la distribucion corriente de las aves de la nacion, del estado, o de la Iocalidad; (2) se desarrolla nueva informacion especialmente sobre especies raras o en peligro; (3) se descubren areas que tienen una avlfauna sobresaliente o habitats raros y ayuda a su proteccion, (4) se documentan cambios de dlstribucion; (5) se pueden usar para documentar cambios de poblacion, especialmente en los tropicos donde otros metodos son mas dificiles de usar porque hay muchas especies y no hay muchos observadores calificados en la identificacion de sonidos de las aves; (6) son proyectos buenos de investigacion para estudiantes graduados; (7) los turistas y los jefes de excursiones de historia natural pueden contribuir con muchas informaciones

  20. Ugo Spirito e il pragmatismo

    OpenAIRE

    Restanio, Franco

    2000-01-01

    Quando appare, nel 1921 presso Vallecchi di Firenze, la prima opera di Ugo Spirito, Il pragmatismo nella filosofia contemporanea, la fugace meteora del pragmatismo in versione italiana è ormai un ricordo sbiadito. Quello che viene considerato il rappresentante massimo, o almeno il più seriamente preparato, di quella meteora, Giovanni Vailati è morto nel1909, all'età di quarantasei aimi. Qualche anno dopo, nel 1914, lo segue, ancora più prematuramente, il collaboratore a lui più...

  1. Cesare Lombroso: il misoneismo e il martirio del folle

    OpenAIRE

    Bertani, Stefano

    2007-01-01

    Il testo illustra, attraversando alcuni dei più noti luoghi della patologia criminale e della devianza lombrosiana, il nesso fra la teoria del folle e il suo rapporto con il male, considerato uno dei punti più dibattuti di tutta la cultura dell’età del progresso. A dispetto dei lunghi anni d’oblio e soprattutto degli stereotipi con cui la figura e l’opera di Cesare Lombroso hanno attraversato il XX secolo, tornare a riflettere su di essi giova ad una miglior comprensione storica, facendo luce...

  2. IL-33 Enhanced the Proliferation and Constitutive Production of IL-13 and IL-5 by Fibrocytes

    Directory of Open Access Journals (Sweden)

    Hisako Hayashi

    2014-01-01

    Full Text Available Interleukin-33 appears to play important roles in the induction of allergic airway inflammation. However, whether IL-33 is involved in airway remodeling remains unclear. Because fibrocytes contribute to tissue remodeling in the setting of chronic inflammation, we examined the effects of IL-33 on fibrocyte functions. Fibrocytes were generated in vitro from peripheral blood mononuclear cells by culturing in the presence of platelet derived growth factors and the cells were stimulated with IL-33. IL-33 enhanced cell proliferation, α-SMA expression, and pro-MMP-9 activity by the fibrocytes without increasing endogenous transforming growth factor-β1 production. Fibrocytes constitutively expressed IL-13 and IL-5, and their production was augmented by stimulation with IL-33. Dexamethasone inhibited the functions of fibrocytes, but IL-33 made fibrocytes slightly refractory to the inhibitory effect of dexamethasone in terms of IL-13 production. Montelukast suppressed IL-13 production by nonstimulated fibrocytes but not those stimulated by IL-33. These findings suggest that IL-33 is involved in the airway remodeling process through its modulation of fibrocyte function independent of antigen stimulation. IL-33 might partially reduce the therapeutic effects of glucocorticoid and cysteinyl leukotriene receptor antagonist on fibrocyte-mediated Th2 responses.

  3. Il GEOatleta moderno

    Directory of Open Access Journals (Sweden)

    Francesco Bartoli

    2006-12-01

    Full Text Available Nell'ultimo decennio gli straordinari sforzi tecnologici hanno evoluto il settore geomatico e portato enormi vantaggi nell'ambito dei cosiddetti servizi a valore aggiunto. Tuttavia la svalutazione commerciale del sistema di navigazione satellitare ha fatto del navigatore un oggetto di uso comune, quasi alla pari del più quotato telefono cellulare. Scemata la corsa al cellulare più modaiolo è subentrata quella al navigatore satellitare più tecnologico con cartografia e punti di interesse più aggiornati. E' assai frequente trovare commercializzazioni degli operatori di telefonia che unisconoal dispositivo mobile il sistema di navigazione, grazie anche apolitiche di businness agreement tra le varie major. L'utilizzo dei dispositivi GPS è davvero ancora arenato alla semplice ricerca di un percorso o di un indirizzo da raggiungere? L'usodi tali apparecchiature può inserirsi all'interno di target quali l'intrattenimento e le attività ricreative? Negli ultimi anni stiamo riscoprendo la bellezza della natura e il piacere di dedicarci ad una serie di attività sportive outdoor che ci conciliano con essa, unendo ai benefici della mente quelli del corpo derivanti da una corretta sollecitazione della propria frequenza cardiaca. Questa mia relazione vuole essere un diario di viaggio nelle quotidiane attività all'aria aperta di un atleta non professionista, praticate durante le quattro stagioni sfruttando le tecnologie legate alla triangolazione satellitare.

  4. IMPREMAS Project, Pilo project for the integration between Environmental Management System and safety Management System; Il Progetto IMPREMAS, Progetto pilota per l'eco-gestion delle Piccole e Medie Imprese classificate a rischio per l'uso e lo stoccaggio di sostanze pericolose previste dal DPR 17.5.1988 n. 175

    Energy Technology Data Exchange (ETDEWEB)

    Luciani, R.; Andriola, L.; Brunetti, N.; Caropreso, G. [ENEA, Centro Ricerche Casaccia, Rome (Italy). Dipt. Ambiente

    1999-07-01

    The topic discussed in this report can be inserted within the context of case studies carried out by ENEA in the promotion of Environmental Management Systems (EMAS-ISO14000). During the IMPREMAS project ENEA has therefore set up a method of integration between Environmental Management System and Safety Management System. [Italian] L'argomento trattato nel presente lavoro si inserisce nel contesto degli studi effettuati dall'ENEA nella promozione dei Sistemi di Gestione Ambientale (EMAS-ISO14000). ENEA durante il progetto IMPREMAS ha sviluppato un metodo per l'integrazione dei Sistemi di Gestione Ambientale con i Sistemi di Gestione della Sicurezza.

  5. Il dono del racconto

    DEFF Research Database (Denmark)

    Polito, Paola

    1998-01-01

    /racconto in prima persona d'una storia di formazione/. Dopo aver individuato, sulla base di considerazioni d'ordine tematico e quantitativo, la prevalenza di tale genere romanzesco (se pure intrecciato ad altri), se ne ricostruiscono le tracce in vari ambiti d'analisi, rilevando in particolare l......: la sua parola segue il percorso esistenziale di cui ci dà testimonianza, l'ostinata ma anche fatale formazione di sé come portavoce epico di un popolo muto e diseredato. La progressiva costituzione del senso della propria vicenda, attraverso una quête che spazia in diversi ambiti, oltre ad essere...

  6. Il muro nella mente:

    Directory of Open Access Journals (Sweden)

    Carmen Concilio

    2013-07-01

    Full Text Available A 78 anni, Nadine Gordimer, premio Nobel per la letteratura nel 1991, è infaticabile: il suo ultimo romanzo The Pick up è stato pubblicato negli Stati Uniti e in Inghilterra, dove ha ricevuto però tiepida accoglienza,e ora anche in Italia1. Alcuni mesi fa, tuttavia, Nadine Gordimer veniva ricordata dai giornali per un’impresa non letteraria: si tratta di un film-documentario dal titolo Johannesburg-Berlin, The Wall in the Mind, che Gordimer ha scritto e che ha girato con suo figlio, Hugo Cassirer, nel 1995-1996.

  7. Il bilinguismo disegnato

    Directory of Open Access Journals (Sweden)

    Graziella Favaro

    2013-07-01

    Full Text Available Il tema della diversità linguistica e del riconoscimento e della valorizzazione delle forme di bilinguismo dei bambini e dei ragazzi è cruciale nella scuola multiculturale e plurilingue. Ma quale rappresentazione della “mente bilingue” hanno i parlanti una o più lingue? Come immaginano la testa di chi e bilingue e dove collocano le diverse parole? Abbiamo chiesto agli alunni, piccoli e grandi, di alcune scuole di “disegnare il bilinguismo”: emergono in maniera vivida i “posti” diversi in cui le lingue si installano, i dubbi e le spiegazioni dei bambini, la necessità del controllo e la coloritura affettiva dell’uno e dell’altro idioma.  Drawing bilingualism The theme of linguistic diversity and the recognition and appreciation of forms of bilingualism in children and young people is crucial in a multilingual, multicultural school environment. But how do speakers of one or more languages imagine a “bilingual mind”? How do they imagine a bilingual person’s head and where are the different words located? We asked school children to “draw bilingualism”. The “placement” of the different languages, the children’s doubts and explanations and their need to check and the affective coloring of one and the other language emerged.

  8. Abitare il paradosso

    Directory of Open Access Journals (Sweden)

    Daniele Capra

    2011-10-01

    Full Text Available L'articolo intende presentare spunti per una rilettura delle tesi esposte da Donald Woods Winnicott secondo una prospettiva filosofica di stampo pragmatico-ermeneutico, con particolare riferimento al tema della istituzione e costituzione della relazione oggettuale, nell’intento di ricercare, rendendolo evidente, il lgouo dvoe un oegtgto copmlesso cmoe qeutsa fsrae asusme un singifiacto e la fliosoifa, sloo in un mdoo più avevrtito riseptto alle sicezne, è psosiblie. To inhabit the paradox The article aims to present ideas for a new reading of theses expounded by Donald Woods Winnicott, according to a philosophical perspective of pragmatic-hermeneutic kind, with special reference to the establishment and constitution of the object relationship, in order to search, making it clear, the palce wehre an ojbect as copmelx as tihs prahse tkeas on a maeinng and piholposhy, olny in a way mroe exerpineced tahn secinecs, is psoislbe.

  9. Il GEOatleta moderno

    Directory of Open Access Journals (Sweden)

    Francesco Bartoli

    2006-12-01

    di tali apparecchiature può inserirsi all'interno di target quali l'intrattenimento e le attività ricreative? Negli ultimi anni stiamo riscoprendo la bellezza della natura e il piacere di dedicarci ad una serie di attività sportive outdoor che ci conciliano con essa, unendo ai benefici della mente quelli del corpo derivanti da una corretta sollecitazione della propria frequenza cardiaca. Questa mia relazione vuole essere un diario di viaggio nelle quotidiane attività all'aria aperta di un atleta non professionista, praticate durante le quattro stagioni sfruttando le tecnologie legate alla triangolazione satellitare.

  10. Interleukin-18 and IL-18 Binding Protein

    NARCIS (Netherlands)

    Dinarello, C.A.; Novick, D.; Kim, S.; Kaplanski, G.

    2013-01-01

    Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines. Similar to IL-1beta, IL-18 is synthesized as an inactive precursor requiring processing by caspase-1 into an active cytokine but unlike IL-1beta, the IL-18 precursor is constitutively present in nearly all cells in healthy humans

  11. Il congiuntivo nel Goldoni

    Directory of Open Access Journals (Sweden)

    Mitja Skubic

    1970-11-01

    Full Text Available Nelle sue commeclie dialettali, Goldoni spesso ricorre al congiuntivo. La forma e tanto frequente e tanta è la coerenza nell'uso che ci testimonia della popolarita del congiuntivo nel veneziano parlato del suo tempo. E ancora non sapremmo elencarne tutte le forme, giacche, nel presente almeno, una speciale per il congiuntivo esiste quasi solo per la 3.a persona (come nell'indicativo, anche nel congiuntivo coincidono la 3.a del sg. e la 3.a del pl.. Pochi sono i verbi che mostrano una forma a parte per il congiuntivo nella La pers. sg. Citiamo dalla Casa nova: »fe conto che sia morto per vu«, I, 6; »E no le vol ehe maledissa sta casa e che diga roba de quel strambo de so fradelo«, II, 5; »se no volè che vaga, lasserò star«, II, 6; »bisognerà che dipenda da ela«, I, 6; »ghe son, bisogna che ghe staga, I, 2; »Bisognerà che m'inzegna da qualche altra banda«, I, 15. Quasi inesistente la 2.a pers. sg.; >>Siestu benedeta, dove che tu xe«, Rusteghi, II, 3. La scarsità della forma nel congiuntivo è da riconnettere alla scarsità della 2.a pers. in generale nelle commedie. Non ci sono forme del congiuntivo nel plurale: »avanti che lo spartimo, fevelo mostrare«, Baruffe, I, 5; »acciò che vegni a discreditar la mia casa«, Rusteghi, II, 3; »son vegnua a posta, acciò che parlè”, Rusteghi, III, 2.

  12. Il bizzarro mondo dei quanti

    CERN Document Server

    Camejo, Silvia Arroyo

    2008-01-01

    Scritto prima dell'esame di maturità da una giovane di eccezionale talento, questo libro colma il vuoto esistente tra la letteratura divulgativa sulla fisica quantistica, che normalmente evita ogni formula matematica, e la letteratura specialistica, ben farcita, invece, di matematica avanzata. L'autrice, appena diciannovenne, con l'ausilio della sola matematica della scuola superiore, introduce il lettore ai principi della fisica dei quanti. Se ne ricava uno sguardo profondo sul microcosmo, il regno affascinante delle particelle elementari: oggetti il cui comportamento si distingue in modo drastico e fondamentale da tutto ciò a cui è avvezzo il nostro umano buonsenso. "Un libro... che avrei desiderato avere a 17 anni". Silvia Arroyo Camejo "In modo assolutamente preciso dal punto di vista fisico, l'autrice spiega con grande passione e divertimento i fondamenti della moderna fisica quantistica ... " Prof. Reinhold A. Bertlmann "Un libro stupefacente di un'autrice straordinaria! Si avverte il suo entusiasmo ...

  13. La materia e il cielo

    Directory of Open Access Journals (Sweden)

    Paolo Zermani

    2012-06-01

    Full Text Available Il testo che l’architetto Paolo Zermani propone per questo convegno si articola in tre parti. La prima è premessa ai due esempi proposti dalla propria vasta attività di progettista. Si tratta di mettere a sbalzo la liminalità dello spazio sacro, ossia il suo costruirsi al limite tra terra e cielo, confine materiale di più ampia significanza simbolica, tra fisica e metafisica, tra elementi evocativi, comunque materiali, e il “cielo dei cieli” di cui parla Agostino.  Intersezione di queste valenze è ancora il tipo architettonico, nella sintesi tra oriente ed occidente offerta dalla cultura romana e dalla forma della croce.Il significato del paesaggio nella composizione dell’architettura è esemplificato nella descrizione di due progetti: il Cimitero di Sansepolcro e il Nuovo Tempio per la Cremazione di Parma, il primo innestato nel Paesaggio Collinare di Piero della Francesca, il secondo incastonato nelle maglie della Limitatio Romana della pianura padana in prossimità di Valera, recinto sacro e nuovo altare della città di Parma. (abstract a cura di Luigi Bartolomei

  14. IL-5 and IL-5 receptor in asthma

    Directory of Open Access Journals (Sweden)

    ATC Kotsimbos

    1997-12-01

    Full Text Available Eosinophils, along with mast cells are key cells involved in the innate immune response against parasitic infection whereas the adaptive immune response is largely dependent on lymphocytes. In chronic parasitic disease and in chronic allergic disease, IL-5 is predominantly a T cell derived cytokine which is particularly important for the terminal differentiation, activation and survival of committed eosinophil precursors. The human IL-5 gene is located on chromosome 5 in a gene cluster that contains the evolutionary related IL-4 family of cytokine genes. The human IL-5 receptor complex is a heterodimer consisting of a unique a subunit (predominantly expressed on eosinophils and a beta subunit which is shared between the receptors for IL-3 & GM-CSF (more widely expressed. The a subunit is required for ligand-specific binding whereas association with the beta subunit results in increased binding affinity. The alternative splicing of the alphaIL-5R gene which contains 14 exons can yield several alphaIL-5R isoforms including a membrane-anchored isoform (alphaIL-5Rm and a soluble isoform (alphaIL-5Rs. Cytokines such as IL-5 produce specific and non-specific cellular responses through specific cell membrane receptor mediated activation of intracellular signal transduction pathways which, to a large part, regulate gene expression. The major intracellular signal transduction mechanism is activation of non-receptor associated tyrosine kinases including JAK and MAP kinases which can then transduce signals via a novel family of transcriptional factors named signal transducers and activators of transcription (STATS. JAK2, STAT1 and STAT 5 appear to be particularly important in IL-5 mediated eosinophil responses. Asthma is characterized by episodic airways obstruction, increased bronchial responsiveness, and airway inflammation. Several studies have shown an association between the number of activated T cells and eosinophils in the airways and abnormalities

  15. IL-1b, IL-6 and IL-8 Levels in Gyneco-Obstetric Infections

    Directory of Open Access Journals (Sweden)

    Beatriz Basso

    2005-01-01

    Full Text Available Objective. During pregnancy cytokines and inflammatory mediators stimulate the expression of prostaglandin, the levels of which determine the onset of labor. The aim of this work was to study interleukin IL-1β, IL-6 and IL-8 levels in the vaginal discharge, serum and urine of pregnant women with genitourinary infection before and after specific treatment. One hundred and fifty-one patients were studied during the second or third trimester of their pregnancy.

  16. INSEGNARE L’ITALIANO L2 NELLA SCUOLA SUPERIORE DI PRIMO GRADO. IL LABORATORIO HOGWARTS: GIOCARE PER IMPARARE

    Directory of Open Access Journals (Sweden)

    Melissa Sala

    2012-07-01

    Full Text Available L’articolo propone un progetto didattico per l’insegnamento dell’italiano L2 nella scuola superiore di primo grado che prevede l’inserimento di studenti stranieri, provenienti da paesi diversi, in un gioco di ruolo didattico ispirato alla saga di Harry Potter.Particolare attenzione è data al laboratorio Hogwarts, un laboratorio specifico il cui obiettivo è quello di promuovere l’interazione, la socializzazione, ma soprattutto l’apprendimento dell’italiano come lingua di comunicazione. La didattica del laboratorio fonde insieme elementi del metodo comunicativo ed elementi del metodo audiolinguale richiamando la didattica ludica in quanto il gioco è assunto come modalità strategica di apprendimento. L’idea che sta alla base del laboratorio Hogwarts è quella di coinvolgere gli apprendenti, stimolarne l’interesse e la curiosità attraverso l’utilizzo di materiale video (visual stimuli e attraverso l’attività ludica che mantiene viva la loro attenzione e la loro motivazione favorendone l’apprendimento linguistico attraverso il divertimento.TEACHING ITALIAN L2 IN MIDDLE SCHOOL. THE HOGWARTS LAB: LEARNNG BY PLAYINGThe article illustrates a project aimed at teaching Italian as a second language. The target audience is middle school students from different countries and with different L1 backgrounds. Students take part in didactic role-plays inspired by the Harry Potter series. Special emphasis is given to the Hogwarts Language Lab, which aims to promote interaction, socialization and second language acquisition. The Lab teaching strategy combines elements of the communicative approach and the audio-lingual method with role-playing. The principle behind the Hogwarts Lab is that the students have to be active participants rather than passive observers. Their involvement can be increased and their interest can be raised through the use of the video input (visual stimuli and role-playing as a teaching strategy. Students are

  17. IL-1β suppresses innate IL-25 and IL-33 production and maintains helminth chronicity.

    Directory of Open Access Journals (Sweden)

    Mario M Zaiss

    Full Text Available Approximately 2 billion people currently suffer from intestinal helminth infections, which are typically chronic in nature and result in growth retardation, vitamin A deficiency, anemia and poor cognitive function. Such chronicity results from co-evolution between helminths and their mammalian hosts; however, the molecular mechanisms by which these organisms avert immune rejection are not clear. We have found that the natural murine helminth, Heligmosomoides polygyrus bakeri (Hp elicits the secretion of IL-1β in vivo and in vitro and that this cytokine is critical for shaping a mucosal environment suited to helminth chronicity. Indeed in mice deficient for IL-1β (IL-1β(-/-, or treated with the soluble IL-1βR antagonist, Anakinra, helminth infection results in enhanced type 2 immunity and accelerated parasite expulsion. IL-1β acts to decrease production of IL-25 and IL-33 at early time points following infection and parasite rejection was determined to require IL-25. Taken together, these data indicate that Hp promotes the release of host-derived IL-1β that suppresses the release of innate cytokines, resulting in suboptimal type 2 immunity and allowing pathogen chronicity.

  18. Interleukin (IL)-13 and IL-4 inhibit proliferation and stimulate IL-6 formation in human osteoblasts: evidence for involvement of receptor subunits IL-13R, IL-13Ralpha, and IL-4Ralpha.

    Science.gov (United States)

    Frost, A; Jonsson, K B; Brändström, H; Ljunghall, S; Nilsson, O; Ljunggren, O

    2001-03-01

    Interleukin-13 (IL-13) inhibits cell proliferation and stimulates interleukin-6 (IL-6) formation in isolated human osteoblasts (hOBs). Because the related cytokine, interleukin-4 (IL-4), is known to exert effects similar to IL-13 in other tissues, and because IL-4 has been implicated as a regulator of bone metabolism, we compared the effects of IL-13 and IL-4 on cell proliferation, IL-6 synthesis, the expression of osteoblastic phenotypic markers in hOB cultures. Also, the receptor proteins mediating these effects in hOBs have been partly characterized. IL-4 and IL-13 dose-dependently inhibited [(3)H]-thymidine incorporation into the DNA of human osteoblasts and stimulated secretion of IL-6 into culture supernatants. IL-13 and IL-4 also increased the mRNA levels of IL-6, as measured by RNAse protection assay. Furthermore, IL-13 and IL-4 dose-dependently enhanced alkaline phosphatase (ALP) activity, but did not affect osteocalcin or collagen type I synthesis. IL-4 was tenfold more potent than IL-13 in inducing both ALP activity and IL-6 secretion, whereas the cytokines were equipotent as inhibitors of cell proliferation. The expression of mRNA for receptor subunits previously implicated in IL-4 and IL-13 signaling was investigated by reverse transcriptase-polymerase chain reaction. IL-13R, IL-13Ralpha, and IL-4Ralpha mRNA were repeatedly detected in hOBs, whereas mRNA for IL-2Rgamma(C) was not detected. Receptor-blocking antibodies to IL-4Ralpha inhibited the induction of IL-6 formation by both IL-4 and IL-13, indicating that both cytokines utilize this receptor subunit in signaling. However, the antibodies did not affect the IL-4/-13-induced inhibition of [(3)H]-thymidine incorporation or the stimulation of alkaline phosphatase (ALP), suggesting that IL-4Ralpha does not mediate these effects of IL-4/-13 in hOBs. We conclude that the cytokines IL-13 and IL-4, through sharing of receptor components, induce similar effects on hOBs, causing inhibition of cell

  19. Data on interleukin (IL)-2- and IL-15-dependent changes in IL-2Rβ and IL-2Rγ complexes

    DEFF Research Database (Denmark)

    Osinalde, Nerea; Sánchez-Quiles, Virginia; Blagoev, Blagoy

    2017-01-01

    -specific phosphorylation events observed both in IL-2Rβ and IL-2Rγ. Moreover, we provide results demonstrating the specific protein recruitment capacity of four of those site-specific phosphorylations. The proteomics and phosphoproteomics data described in this article is associated with a research article entitled...

  20. 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)

  1. Il progetto SISTER per il comune di Lignano Sabbiadoro

    OpenAIRE

    Alberto Poli

    2005-01-01

    Il comune di Lignano è stato recentemente invitato a Roma in qualità di relatore alla conferenza nazionale dei sistemi informativi territoriali organizzata da Esri, il maggior produttore mondiale di software per la gestione delle cartografie informatizzate. In tale occasione l’assessore AngeloBonelli ha presentato il progetto sperimentale di sistema informatico per la gestione del territorio, che è in corso da circa un anno. Ecco la sintesi della relazione del Sistema Informativo Integrato Te...

  2. Il progetto SISTER per il comune di Lignano Sabbiadoro

    Directory of Open Access Journals (Sweden)

    Alberto Poli

    2005-10-01

    Full Text Available Il comune di Lignano è stato recentemente invitato a Roma in qualità di relatore alla conferenza nazionale dei sistemi informativi territoriali organizzata da Esri, il maggior produttore mondiale di software per la gestione delle cartografie informatizzate. In tale occasione l’assessore AngeloBonelli ha presentato il progetto sperimentale di sistema informatico per la gestione del territorio, che è in corso da circa un anno. Ecco la sintesi della relazione del Sistema Informativo Integrato Territoriale (SISTER realizzato da Politecnica.

  3. IL CAMPO GEOMAGNETICO

    Directory of Open Access Journals (Sweden)

    F. MOLINA

    1972-06-01

    Full Text Available Questo lavoro non è un trattato sul campo geomagnetico e nemmeno
    una rassegna sull'argomento, almeno nel significato che normalmente
    si attribuisce al termine « rassegna »; esso è semplicemente
    un tentativo di condensare in termini comprensibili agli studiosi non
    specializzati ciò che oggi si sa o si ipotizza sul magnetismo terrestre
    e sulle sue cause. Chi scrive si è sempre trovato a disagio di fronte
    alle richieste di una spiegazione sull'origine del campo magnetico
    terrestre: o si cerca di cavarsela con poche parole (« si tratta di correnti
    elettriche indotte nell'interno della Terra » che possono forse accontentare
    chi non si occupa in modo particolare di problemi scientifici
    ma non possono soddisfare un fisico, oppure ci si sente obbligati a
    tentare faticosamente di approfondire, sia per capirli personalmente
    che per poterli poi spiegare agli altri, argomenti e ragionamenti che
    sono in realtà accessibili solo a un fisico teorico ben preparato. Apparentemente
    non esiste una via di mezzo, come del resto in molti altri
    campi della fisica contemporanea.
    La presente monografia rappresenta appunto il tentativo di trovare
    questa via di mezzo: nel terzo capitolo, dedicato alle teorie sull'origine
    del campo geomagnetico, si cerca di descrivere qualitativamente
    i principali processi fisici proposti come sorgenti del campo,
    dopo un accenno ai fondamenti fisici e matematici sui quali sono state
    elaborate le varie teorie. Senza farmi soverchie illusioni di essere riuscito
    nell'intento, mi dichiarerei tuttavia soddisfatto se questo lavoro
    destasse sull'argomento l'interesse di qualche giovane ricercatore, incoraggiandolo
    ad un approfondimento.

  4. Il discreto e il continuo complementarita in matematica

    CERN Document Server

    Kuyk, Willem

    1982-01-01

    Nato dall'esperienza didattica dell'autore, il libro si presenta come un testo interdisciplinare di matematica e di filosofia, inteso a fornire un quadro complessivo dello stato attuale dei fondamenti della matematica.

  5. Il collasso dell'Antartide

    OpenAIRE

    Florindo, F.; Boschi, E.

    2009-01-01

    Negli ultimi anni il problema del riscaldamento globale del nostro pianeta (global warming) e del contributo della civiltà moderna all’incremento dei livelli di gas serra ha assunto sempre più rilevanza nell’ambito della comunità scientifica e politica. Nel corso del XX secolo il riscaldamento medio globale è stato di 0.7°C e una delle ultime proiezioni attuate dal Comitato Intergovernativo sui Cambiamenti Climatici (Ipcc-2007) indica che entro il 2100 la temperatura sarà...

  6. Method to allow the estimation of heat transfer coefficients in solar stills; Metodo para determinar coeficientes locales de transferencia de calor en destiladores solares

    Energy Technology Data Exchange (ETDEWEB)

    Rubio Cerda, Eduardo; Porta Gandara, Miguel A [CIBNOR, Mexico D.F (Mexico); Fernandez Zayas, Jose Luis [UNAM Mexico, D.F. (Mexico)

    2000-07-01

    This work reports an experimental method that allows to estimate the heat transfer coefficients in the neighborhood of walls or flat plates subject to convective transport phenomena. This method can be applied to a great variety of thermal systems since it is based on the knowledge of the border condition for the temperature at the surface of the plate, and the temperature profile that characterize the dimensionless coefficient of heat transfer in the fluid, according to its definition given by the Nusselt number. The approach of this work are the foundations of the method and the system that has been developed to apply it, that incorporates automatic acquisition equipment for continuos monitoring of the information and elements to control the parameters of interest. In addition, the experimental cavities on which the method will be evaluated are discussed, considering two different scales, as well as experiments in cavities filled with air, and with a mixture of air and steam water, as is the case for solar distillation. [Spanish] En este trabajo se presenta un metodo que permite determinar de manera experimental coeficientes de transferencia de calor por conveccion. Este metodo puede ser aplicado a una gran variedad de sistemas termicos ya que se fundamenta en el conocimiento de la condicion de frontera para la temperatura en la superficie de la placa, y del perfil de temperaturas que caracteriza el coeficiente adimensional de transferencia de calor en el fluido, de acuerdo a la definicion de este, dada por el numero de Nusselt. El trabajo que aqui se reporta esta enfocado a la fundamentacion del metodo y al equipamiento que se ha desarrollado para instrumentarlo, que incorpora equipos automaticos de adquisicion continua de informacion y elementos de control para los parametros de interes. Se presentan ademas, las cavidades experimentales sobre las que sera evaluado el metodo, que considera dos escalas diferentes, asi como experimentos en cavidades llenas de aire

  7. Končni rezultat zdravljenja starostnika z zlomom vratu stegnenice je povezan z metodo operacije

    Directory of Open Access Journals (Sweden)

    Drago Brilej

    2007-12-01

    Full Text Available Izhodišča: Prebivalstvo Slovenije se stara. Med starostniki so zlomi kolkov pomemben vzrok umrljivosti in invalidnosti. Incidenca zlomov vratu stegnenice dosega 25–30 na 100.000 prebivalcev letno. Mnenja o načinu zdravljenja starostnikov z zlomom vratu stegnenice si nasprotujejo. Kar 94 % dislociranih zlomov vratu stegnenice pri starostnikih na Nizozemskem zdravijo s hemiartroplastiko, v Švedski pa praktično vse primarno oskrbijo z osteosintezo. V SUB Celje so do leta 1994 večino dislociranih zlomov vratu stegnenice oskrbeli z osteo sintezo s tremi vijaki. Leta 1995 so spremenili protokol zdravljenja. Poškodovance, starejše od 65 let z dislociranim zlomom vratu stegnenice so oskrbeli z delno cementirano bipolarno protezo. Obe skupini so primerjali med sabo, da bi ugotovili upravičenost menjave metode zdravljenja. Hipoteza je bila, da vstavitev delno cementirane bipolarne endoproteze izboljša preživetje starostnikov z dislociranim zlomom vratu stegnenice in da preživelim omogoči uspešnejšo rehabilitacijo.Bolniki in metode: V SUB Celje so od januarja 1993 do decembra 1996 zaradi svežega dislociranega zloma vratu stegnenice (Garden 3,4 zdravili 164 poškodovancev, starejših od 65 let. Praviloma so v letih 1993 in 94 zdravili te zlome z osteosintezo s tremi vijaki, v letih 1995 in 96 z vstavitvijo delne bipolarne endoproteze. 131 (80 % poškodovancev so spremljali 1 leto. Glede na način oskrbe zloma so jih razdelili v dve skupini. V letih 1993 in 94 so zdravili 52 starostnikov zaradi dislociranega zloma vratu stegnenice z osteosintezo s tremi vijaki. V letih 1995 in 96 so zdravili 81 starostnikov zaradi dislociranega zloma vratu stegnenice z delno cementirano bipolarno protezo. Pred operativnim posegom so ocenili zdravstveno stanje poškodovanca po ASA lestvici. Ugotavljali so zaplete med zdravljenjem in trajanje hospitalizacije. Ob koncu zdravljenja in po enem letu so ocenili samostojnost poškodovancev pri hoji. Z metodo po

  8. IL6 and IL10 are genetic susceptibility factors of periodontal disease

    Directory of Open Access Journals (Sweden)

    Luca Scapoli

    2012-01-01

    Conclusions: The present investigation indicated that polymorphisms of IL6 and IL10 constitute risk factors for chronic periodontitis, while there was no evidence implicating a specific IL1A or IL1B genotype.

  9. Microscale adaptation of the potentiometric method with ion-selective electrode for the quantification of fluoride; Adaptacion a microescala del metodo potenciometrico con electrodo ion selectivo para la cuantificacion de fluoruro

    Energy Technology Data Exchange (ETDEWEB)

    Guevara Ruiz, Paulina; Ortiz Perez, Maria Deogracias [Laboratorio de Bioquimica, Facultad de de Medicina, Universidad Autonoma de San Luis Potosi, San Luis Potosi, San Luis Potosi, (Mexico)]. E-mail: mdortiz@uaslp.mx

    2009-05-15

    Similarly to other countries, ground water from Mexico is naturally polluted by fluoride. The main effects of fluoride at typical ground water concentrations are dental fluorosis, neurological deficits and reproductive disorders. In order to verify that the fluoride concentration is within the allowed guideline in Mexico (NOM 127 and 201), it is important to monitor fluoride levels in water and commercial beverages. The aim of this work is to develop a modification of the standard potentiometric method for fluoride determination in water, in order to reduce costs and amount of potentially toxic waste substances. Both methods were validated, the standard potentiometric method with the ion selective electrode and the microscale modification proposed in this paper. The methods were compared using statistic tests and graphics, followed by the comparison of 125 samples of commercial bottled water sold in the city of San Luis Potosi. Optimal results were obtained for the validation of both methods, and the microscale modification showed statistically identical results to those obtained with the standard method in all samples of bottled water. The microscale modification is a good alternative for fluoride assessment in water and beverages, and it represents a 95 % reduction of costs and chemical waste. [Spanish] En varios paises, incluido Mexico se presenta una contaminacion natural con fluoruro en agua subterranea; los principales efectos en la salud observados en poblacion expuesta a concentraciones mayores al valor permisible (que en Mexico es de 1.5 mg/L) son la fluorosis dental y esqueletica, asi como dano reproductivo y neurologico. En varios estados de la republica Mexicana, este problema es aun desconocido, de ahi la necesidad de evaluar las concentraciones de fluoruro en agua de consumo en varias comunidades. Asi, el objetivo de este trabajo es desarrollar un metodo a microescala para la determinacion de fluoruro en agua, que al reducir la cantidad de reactivo y

  10. Association study of functional polymorphisms in interleukins and interleukin receptors genes: IL1A, IL1B, IL1RN, IL6, IL6R, IL10, IL10RA and TGFB1 in schizophrenia in Polish population.

    Science.gov (United States)

    Kapelski, Pawel; Skibinska, Maria; Maciukiewicz, Malgorzata; Wilkosc, Monika; Frydecka, Dorota; Groszewska, Agata; Narozna, Beata; Dmitrzak-Weglarz, Monika; Czerski, Piotr; Pawlak, Joanna; Rajewska-Rager, Aleksandra; Leszczynska-Rodziewicz, Anna; Slopien, Agnieszka; Zaremba, Dorota; Twarowska-Hauser, Joanna

    2015-12-01

    Schizophrenia has been associated with a large range of autoimmune diseases, with a history of any autoimmune disease being associated with a 45% increase in risk for the illness. The inflammatory system may trigger or modulate the course of schizophrenia through complex mechanisms influencing neurodevelopment, neuroplasticity and neurotransmission. In particular, increases or imbalance in cytokine before birth or during the early stages of life may affect neurodevelopment and produce vulnerability to the disease. A total of 27 polymorphisms of IL1N gene: rs1800587, rs17561; IL1B gene: rs1143634, rs1143643, rs16944, rs4848306, rs1143623, rs1143633, rs1143627; IL1RN gene: rs419598, rs315952, rs9005, rs4251961; IL6 gene: rs1800795, rs1800797; IL6R gene: rs4537545, rs4845617, rs2228145, IL10 gene: rs1800896, rs1800871, rs1800872, rs1800890, rs6676671; IL10RA gene: rs2229113, rs3135932; TGF1B gene: rs1800469, rs1800470; each selected on the basis of molecular evidence for functionality, were investigated in this study. Analysis was performed on a group of 621 patients with diagnosis of schizophrenia and 531 healthy controls in Polish population. An association of rs4848306 in IL1B gene, rs4251961 in IL1RN gene, rs2228145 and rs4537545 in IL6R with schizophrenia have been observed. rs6676671 in IL10 was associated with early age of onset. Strong linkage disequilibrium was observed between analyzed polymorphisms in each gene, except of IL10RA. We observed that haplotypes composed of rs4537545 and rs2228145 in IL6R gene were associated with schizophrenia. Analyses with family history of schizophrenia, other psychiatric disorders and alcohol abuse/dependence did not show any positive findings. Further studies on larger groups along with correlation with circulating protein levels are needed. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis.

    Directory of Open Access Journals (Sweden)

    Paméla Gasse

    Full Text Available BACKGROUND: Idiopathic pulmonary fibrosis is a devastating as yet untreatable disease. We demonstrated recently the predominant role of the NLRP3 inflammasome activation and IL-1β expression in the establishment of pulmonary inflammation and fibrosis in mice. METHODS: The contribution of IL-23 or IL-17 in pulmonary inflammation and fibrosis was assessed using the bleomycin model in deficient mice. RESULTS: We show that bleomycin or IL-1β-induced lung injury leads to increased expression of early IL-23p19, and IL-17A or IL-17F expression. Early IL-23p19 and IL-17A, but not IL-17F, and IL-17RA signaling are required for inflammatory response to BLM as shown with gene deficient mice or mice treated with neutralizing antibodies. Using FACS analysis, we show a very early IL-17A and IL-17F expression by RORγt(+ γδ T cells and to a lesser extent by CD4αβ(+ T cells, but not by iNKT cells, 24 hrs after BLM administration. Moreover, IL-23p19 and IL-17A expressions or IL-17RA signaling are necessary to pulmonary TGF-β1 production, collagen deposition and evolution to fibrosis. CONCLUSIONS: Our findings demonstrate the existence of an early IL-1β-IL-23-IL-17A axis leading to pulmonary inflammation and fibrosis and identify innate IL-23 and IL-17A as interesting drug targets for IL-1β driven lung pathology.

  12. Torque calculation in the induction motor with the finite element method; Calculo del par en el motor de induccion con el metodo del elemento finito

    Energy Technology Data Exchange (ETDEWEB)

    Castillo Diaz, Ramon

    2002-06-15

    In this work the method of the finite element is applied to the bi-dimensional analysis of the induction motor in operation in steady state, excited by sine sources of laminar currents and sine sources of voltage. The analysis is focused mainly in the calculation of the electromagnetic torque. The topics of electromagnetic theory are covered and in an idealized model of the induction motor, analytically and numerically with the method of the finite element, in the variant method of Galerkin, the vectorial potential and the torque are calculated. The results obtained with the analytical and numerical methods are compared. Three formulations are developed to calculate the torque with the method of the finite element, using triangular elements of first order, based in the equation of force of Lorentz, the Maxwell tensor and the principle of the virtual work. Finally, a motor of induction of real characteristics is simulated, assuming it is connected to a three-phase voltage source. In this motor it is analyzed the convergence and the evolution in the results obtained of the torque with different discretions, and the torque-velocity performance curve is calculated. [Spanish] En este trabajo se aplica el metodo del elemento finito al analisis bidimensional del motor de induccion en operacion en estado estable, excitado por fuentes de corriente laminar senoidales y fuentes de voltaje senoidales. El analisis se enfoca principalmente en el calculo del par electromagnetico. Se tratan los topicos de teoria electromagnetica involucrados y en un modelo idealizado del motor de induccion, se calculan analitica y numericamente con el metodo del elemento finito, en la variante metodo de Galerkin, el potencial vectorial y el par. Se comparan resultados obtenidos con los metodos analiticos y numericos. Se desarrollan tres formulaciones para calcular el par con el metodo del elemento finito, utilizando elementos triangulares de primer orden, basadas en la ecuacion de fuerza de

  13. Il vaso e i cocci. Note in margine a La llegenda del llibreter assassí de Barcelona

    Directory of Open Access Journals (Sweden)

    Francesco de Cristofaro

    2013-12-01

    Full Text Available Il contributo discute alcune questioni legate, in modo più o meno tangenziale, a La llegenda del llibreter assassí de Barcelona: dopo aver sottoposto il libro di Ramon Miquel i Planas alle domande, di metodo e di merito, presenti in un affine e più recente “giallo filologico” (il saggio di Alberto Varvaro sulla vicenda della baronessa di Carini, e dopo essersi interrogato circa il filone paraletterario delle cosiddette “Cause celebri” e circa una declinazione naturalista e straniante della letteratura processuale (il dittico di Galdós Realidad-Incógnita, il discorso si sposta su di un aspetto più prettamente storico-culturale e tematico quale l’intreccio fra bibliomania e cleptomania (soprattutto in Flaubert. L’articolo si conclude con una rapida ricognizione dei plagi letterari realizzati da Nodier, il presunto colpevole del falso da cui si diparte tutta la genealogia indagata da Miquel i Planas: un colpevole che, proprio mentre si macchia di molteplici crimini letterari, dedica loro un sofisticato trattato giurisprudenziale, in cui sistematizza e stigmatizza quegli stessi crimini This essay seeks to investigate tangentially some questions regarding La llegenda del llibreter assassí de Barcelona: after having analyzed the approaches, methods and strategies –that Alberto Varvaro has thoroughly examined in the essay on Baroness di Carini’s story–, and the literary quality achieved by Ramon Miquel i Planas in his work; and after having probed the paraliterary line of the so-called “famous trials” –mostly focusing on the naturalistic estrangement effect produced by literature works related to legal cases (e.g. the conventional diptych in Galdós’s Realidad-Incógnita–, the centre of attention shifts on the cultural, historical aspects of the bizarre relationship between kleptomania and bibliomania (especially in Flaubert. The article concludes with a swift overview of literary plagiarisms committed by Nodier, the

  14. Quantitative Contribution of IL2Rγ to the Dynamic Formation of IL2-IL2R Complexes.

    Directory of Open Access Journals (Sweden)

    Luis F Ponce

    Full Text Available Interleukin-2 (IL2 is a growth factor for several immune cells and its function depends on its binding to IL2Rs in the cell membrane. The most accepted model for the assembling of IL2-IL2R complexes in the cell membrane is the Affinity Conversion Model (ACM. This model postulates that IL2R receptor association is sequential and dependent on ligand binding. Most likely free IL2 binds first to IL2Rα, and then this complex binds to IL2Rβ, and finally to IL2Rγ (γc. However, in previous mathematical models representing this process, the binding of γc has not been taken into account. In this work, the quantitative contribution of the number of IL2Rγ chain to the IL2-IL2R apparent binding affinity and signaling is studied. A mathematical model of the affinity conversion process including the γ chain in the dynamic, has been formulated. The model was calibrated by fitting it to experimental data, specifically, Scatchard plots obtained using human cell lines. This paper demonstrates how the model correctly explains available experimental observations. It was estimated, for the first time, the value of the kinetic coefficients of IL2-IL2R complexes interaction in the cell membrane. Moreover, the number of IL2R components in different cell lines was also estimated. It was obtained a variable distribution in the number of IL2R components depending on the cell type and the activation state. Of most significance, the study predicts that not only the number of IL2Rα and IL2Rβ, but also the number of γc determine the capacity of the cell to capture and retain IL2 in signalling complexes. Moreover, it is also showed that different cells might use different pathways to bind IL2 as consequence of its IL2R components distribution in the membrane.

  15. Direct regulation of IL-2 by curcumin.

    Science.gov (United States)

    Oh, Jin-Gyo; Hwang, Da-Jeong; Heo, Tae-Hwe

    2018-01-01

    Interleukin-2 (IL-2) is a crucial growth factor for both regulatory and effector T cells. Thus, IL-2 plays a critical role in the stimulation and suppression of immune responses. Recently, anti-IL-2 antibodies (Abs) have been shown to possess strong IL-2 modulatory activities by affecting the interaction between IL-2 and IL-2 receptors. In this study, we screened an herbal library to identify a compound that regulates IL-2, which resulted in the identification of curcumin as a direct binder and inhibitor of IL-2. Curcumin is a phytochemical with well-known anti-cancer properties. In this study, curcumin mimicked or altered the binding pattern of anti-IL-2 Abs against IL-2 and remarkably inhibited the interaction of recombinant IL-2 with the IL-2 receptor α, CD25. Interestingly, curcumin neutralized the biological activities of IL-2 both in vitro and in vivo. In this report, we elucidated the unsolved mechanism of the anti-cancer effect of curcumin by identifying IL-2 as a direct molecular target. Curcumin, as a small molecule IL-2 modulator, has the potential to be used to treat IL-2 related pathologic conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Il libro agente della socializzazione

    Directory of Open Access Journals (Sweden)

    Daniela Sideri

    2017-06-01

    Full Text Available Il saggio indaga il ruolo del libro come agente di socializzazione, con particolare riferimento al pubblico dei lettori ragazzi e bambini e alle specifiche funzioni formative della “lettura della letteratura” in età pre-scolare e scolare fino ai 14 anni. La ricerca di matrice socio-culturale si è occupata per lo più del libro in qualità di prodotto eminentemente sociale (sociologia della letteratura, contenitore di testi significanti (semiotica, e bene di consumo dell’industria culturale (cultural studies: lo studio proposto richiama le conclusioni fondamentali di decenni di studi intorno al libro, con l’intento di rintracciare i criteri adeguati (tema, target, identità visiva, funzione pratica e utopica a guidare una classificazione dei generi 0-14 che evidenzi il valore socializzante di ciascuno, proponendo così una originale tipologia, che giustifica l’inserimento del libro tra quelle definite “agenzie testuali” della socializzazione.

  17. Il potere di Prometeo e il dovere di Kant

    Directory of Open Access Journals (Sweden)

    Stefano Picchetti

    2006-10-01

    Full Text Available Kant ci suggerisce qualcosa che Prometeo e il mito greco avevano già accennato. L'imperativo che pone freno al fare, è già in sé nel soggetto ed è per questo che egli che egli è responsabile delle proprie azioni, indipendentemente dalla legge scritta.

  18. Il progetto SISTER per il comune di Lignano Sabbiadoro

    Directory of Open Access Journals (Sweden)

    Alberto Poli

    2005-10-01

    Bonelli ha presentato il progetto sperimentale di sistema informatico per la gestione del territorio, che è in corso da circa un anno. Ecco la sintesi della relazione del Sistema Informativo Integrato Territoriale (SISTER realizzato da Politecnica.

  19. Il Sole, il genoma e Internet strumenti delle revoluzioni scientifiche

    CERN Document Server

    Dyson, Freeman J

    2000-01-01

    In queste appassionate conferenze «di soglia» Dyson si sporge sul domani con la visionarietà di un Verne o di un Wells, consapevole però di abbozzare «solo uno dei corsi possibili, tra i milioni di altri che il futuro potrà riservarci». Il nuovo trivio di forze rivoluzionarie che, secondo il modello di Dyson, muoverà lo sviluppo ha nomi noti a tutti, e disputati da molti: energia solare, ingegneria genetica, rete di comunicazione globale. Un loro utilizzo flessibile e sinergico arriverebbe a ridisegnare il paesaggio sociale del pianeta, facendo affluire verso aree depresse risorse ora concentrate in pochi paesi, e ridando vita ovunque all'economia di villaggio. La raccolta di energia da una fonte equidistribuita come la luce solare potrebbe infatti avvenire attraverso coltivazioni arboree manipolate genetica mente allo scopo, con costi sostenibili e senza pregiudizio della ecodiversità. Sia che guardi al prossimo futuro terrestre sia che contempli la prospettiva non troppo lontana di insediamenti uma...

  20. Il programma dell'universo

    CERN Document Server

    Lloyd, Seth

    2006-01-01

    Da quando l'universo ha avuto inizio, ha cominciato a calcolare il proprio comportamento. All'inizio il computer-universo produceva strutture semplici, particelle elementari e leggi elementari della fisica; col passare del tempo ha processato "informazioni" sempre più complesse, producendo strutture sempre più intricate (galassie, stelle, pianeti), ma sempre secondo leggi semplici. Ogni cosa deve quindi la propria esistenza alla capacità intrinseca della materia e dell'energia di processare informazione. Se si decifrasse fino in fondo si potrebbe, con un computer quantistico di dimensioni ridotte, comprendere l'universo nel suo insieme.

  1. Ri-Costruiamo il futuro

    Directory of Open Access Journals (Sweden)

    Guido Maria Amorati

    2012-12-01

    Full Text Available Viene di seguito presentato un report della conferenza “Ri-Costruiamo il futuro” che si è tenuta il 3 ottobre 2012 presso la Facoltà di Ingegneria dell’Università di Bologna. L’evento è stato organizzato e promosso da Edarchibo, la rivista on line dela corso di Laurea in Ingegneria edile-architettura. Alcuni docenti hanno risposto alle domande degli studenti circa le possibilità professionali post-laurea e la ricostruzione a seguito del terremoto.

  2. Il Dio dell'Eriugena

    Directory of Open Access Journals (Sweden)

    Silvia Magnavacca

    2008-07-01

    Full Text Available In un universo interpretato come sogno da decifrare, la metafisica è lo strumento, secondo Borges, con cui l’uomo tenta di rendere coerente questo sogno. Il pensiero di Eriugena è particolarmente affascinante per Borges, in quanto accetta la sfida della veritigine: un Dio che dal nulla della sua indeterminatezza dà luogo al mondo, dispiegandosi negli archetipi che popolano il sogno dell’universo. Una fantastica metafisica che allontana dall’uomo lo sgomento per la condanna alla propria individualità.

  3. Linkage and association studies of IL1B and IL1RN gene polymorphisms in preeclampsia

    NARCIS (Netherlands)

    Lachmeijer, AMA; Nosti-Escanilla, MP; Bastiaans, EB; Pals, G; Sankuijl, LA; Kostense, PJ; Aarnoudse, JG; Crusius, JBA; Pena, AS; Dekker, GA; Arngrimsson, R; ten Kate, LP

    2002-01-01

    Objective: To determine whether preeclampsia is either associated with or linked to two polymorphisms in the IL1B gene (IL1B-TaqI and IL1B-511) and one polymorphism in the IL1RN gene (IL1RN-IVS2). Methods: Genotyping was performed in 150 affected sib-pair families and 104 healthy Dutch blood donors.

  4. Role of IL-38 and Its Related Cytokines in Inflammation

    Directory of Open Access Journals (Sweden)

    Xianli Yuan

    2015-01-01

    Full Text Available Interleukin- (IL- 38 is a recently discovered cytokine and is the tenth member of the IL-1 cytokine family. IL-38 shares structural features with IL-1 receptor antagonist (IL-1Ra and IL-36Ra. IL-36R is the specific receptor of IL-38, a partial receptor antagonist of IL-36. IL-38 inhibits the production of T-cell cytokines IL-17 and IL-22. IL-38 also inhibits the production of IL-8 induced by IL-36γ, thus inhibiting inflammatory responses. IL-38-related cytokines, including IL-1Ra and IL-36Ra, are involved in the regulation of inflammation and immune responses. The study of IL-38 and IL-38-related cytokines might provide new insights for developing anti-inflammatory treatments in the near future.

  5. Flow measurement in a 170-MW hydraulic turbine using the Gibson method; Medicion del flujo de una turbina hidraulica de 170 MW utilizando el metodo Gibson

    Energy Technology Data Exchange (ETDEWEB)

    Urquiza, Gustavo [Universidad Autonoma del Estado de Morelos (Mexico); Adamkowski, Adam [The Szewalski Institute of Fluid-Flow Machinery (Poland); Kubiak, Janusz; Sierra, Fernando [Universidad Autonoma del Estado de Morelos (Mexico); Janicki, Waldemar [The Szewalski Institute of Fluid-Flow Machinery (Poland); Fernandez, J. Manuel [Comision Federal de Electricidad (Mexico)

    2007-07-15

    This paper describes the methodology applied for measuring water flow through a 170-MW hydraulic turbine. The flow rate was measured using the pressure-time method, also known as the Gibson method. This method uses the well-known water hammer phenomenon in pipelines; in turbine penstocks, for instance. The version of this method used here is based on measuring, during total stop of the water stream, the time-history of pressure change in one section of the turbine penstock and relate it to the pressure in the upper reservoir to which the penstock is connected. The volumetric flow rate is determined from the relevant integration of the measured temporary pressure rise. Flow measurement was possible this way because the influence of the penstock inlet was negligible as far as an error of the measurement is concerned. The length of the penstock was 300 m. Previous experience and a standard IEC-41-1991 were the criteria adopted and applied. A fast and efficient acquisition system, including a 16 bit card, was used. The flow rate was calculated using a computer program developed and tested on several cases. The results obtained with the Gibson method were used for calibration of the on-line flow measuring system based on the Winter-Kennedy method as one of the index methods. This method is very often used for continuous monitoring of the flow rate through hydraulic turbines, when the calibration has been done on site by using the results of measurements obtained by the absolute method. Having measured the flow rate and output power, the efficiency was calculated for any operating conditions. A curve showing the best operating conditions based on the highest efficiency is presented and discussed. The details of the instrumentation, its installation, and the results obtained are discussed in the paper. [Spanish] Este articulo describe la metodologia aplicada para la medicion del flujo en una turbina hidraulica de 170 MW. El flujo se midio utilizando el metodo de presion

  6. Clinical significance of measurement of changes of serum IL-6, IL-18 and IL-1β levels after treatment in patients with endometriosis

    International Nuclear Information System (INIS)

    Zhang Chunyan; Zhang Shumin; Zhou Dongxia; Wang Enbo

    2008-01-01

    Objective: To explore the clinical significance of changes of serum IL-6, IL-18 and IL-1β levels after treatment in patients with endometriosis. Methods: Serum IL-6 (with RIA) and IL-18, IL-1β (with ELISA) levels were determined in 38 patients with endometriosis both before and after treatment as well as 35 controls. Results: Before treatment, the serum IL-6, IL- 18 and IL-1β levels were significantly higher in the patients than those in controls (P 0.05). Conclusion: Detection of serum IL-6, IL-18 and IL- 1β levels might reflect the progress of diseases in patients with endometriosis. (authors)

  7. Flow in potential cascades by means of the finite element method; Flujo en cascadas potenciales mediante el metodo del elemento finito

    Energy Technology Data Exchange (ETDEWEB)

    Sosa Cordero, Rodolfo; Fernandez Valencia, Gonzalo [Instituto de Investigaciones Electricas, Cuernavaca (Mexico)

    1986-12-31

    This article presents a mathematical model and its solution by means of the finite element method with approximate Garlekin formulation, for the flow analysis in a circular cascade, in a surface of revolution current of a turbo- machine, that can be axial, mixed or radial. To the revolution surface an agreed transformation is applied to obtain a plane, eliminating in this form one term in the equation succeeding in avoiding an iterative solution. Likewise, the finite element method allows to solve the equation in partial derivatives of the elliptical type in its quasi-harmonic form. Additionally, the method followed to introduce the contour conditions is presented; specially, the Kutta-Joukowsky conditions and the one of periodicity, which distinguishes this problem from the classical problems of ideal flows evaluated in the contour. [Espanol] En este articulo se presenta un modelo matematico y su solucion mediante el empleo del metodo del elemento finito con formulacion aproximada de Galerkin, para el analisis del flujo en una cascada circular, en una superficie de corriente de revolucion de una turbomaquina, que puede ser axial, mixta o radial. A la superficie de revolucion se le aplica una transformacion conforme para obtener un plano, eliminando de esta forma un termino en la ecuacion logrando evitar la solucion iterativa. Asimismo, el metodo del elemento finito permite resolver la ecuacion en derivadas parciales del tipo eliptico en su forma cuasiarmonica. Se presenta, ademas, el metodo seguido para introducir las condiciones de contorno; en especial, las condiciones de Kutta-Joukowsky y la de periodicidad, que distinguen a este problema de los problemas clasicos de flujos ideales valuados en el contorno.

  8. IL-6 Receptor Isoforms and Ovarian Cancer

    Science.gov (United States)

    2013-01-01

    2 mice were normal in appearance and were born in the expected Mendelian ratio. Il6ra2/2 mice have a defective response to IL-6 IL-6 is critical for...improved wound contraction in Il62/2 mice (Fig. 5F, 5G), similar to data obtained in mice with a combined genetic deficit of IL-6 and IL-6Ra. These data...specificity from the cytokine receptor gp130. Trends Genet . 20: 23–32. The Journal of Immunology 7227 at U niv of C incinnati Serials R eceiving A cq D ept

  9. Elevated levels of circulating IL-7 and IL-15 in patients with early stage prostate cancer

    Directory of Open Access Journals (Sweden)

    Bachmann Alexander

    2011-09-01

    Full Text Available Abstract Background Chronic inflammation has been suggested to favour prostate cancer (PCA development. Interleukins (IL represent essential inflammation mediators. IL-2, IL-7, IL-15 and IL-21, sharing a common receptor γ chain (c-γ, control T lymphocyte homeostasis and proliferation and play major roles in regulating cancer-immune system interactions. We evaluated local IL-2, IL-7, IL-15 and IL-21 gene expression in prostate tissues from patients with early stage PCA or benign prostatic hyperplasia (BPH. As control, we used IL-6 gene, encoding an IL involved in PCA progression. IL-6, IL-7 and IL-15 titres were also measured in patients' sera. Methods Eighty patients with BPH and 79 with early (1 to 2c stage PCA were enrolled. Gene expression in prostate tissues was analyzed by quantitative real-time PCR (qRT-PCR. Serum IL concentrations and acute phase protein titres were evaluated by ELISA. Mann-Whitney, Wilcoxon and χ2 tests were used to compare IL gene expression and serum titers in the two groups of patients. Receiver operating characteristic (ROC curves were constructed to evaluate the possibility to distinguish sera from different groups of patients based on IL titers. Results IL-2 and IL-21 gene expression was comparably detectable, with low frequency and at low extents, in PCA and BPH tissues. In contrast, IL-6, IL-7 and IL-15 genes were expressed more frequently (p Conclusions Expression IL-7 and IL-15 genes in prostate tissues and corresponding serum titres are significantly increased in patients with early stage PCA as compared with patients with BPH.

  10. Method of identifying the friction of rotors using the wavelet transform; Metodo para identificar el rozamiento de rotores utilizado la transformada wavelet

    Energy Technology Data Exchange (ETDEWEB)

    Jauregui Correa, Juan Carlos; Rubio Cerda, Eduardo; Gonzalez Brambila, Oscar [CIATEQ, A.C., Queretaro (Mexico)

    2007-11-15

    The modern processes of signal analysis that measure mechanical vibrations are based on the fast transform of Fourier (FFT), nevertheless, this method is not able to identify transient phenomena nor of nonlinear nature. Although many efforts have been made to try to identify these phenomena in the frequency spectra, it is not possible to correlate the spectra with the physical characteristics of this type of phenomena. Within these phenomena on the rubbing of a rotor against the housing or trunnion of a bearing, this phenomenon has a nonlinear behavior, as it is demonstrated in this paper. In the first part a method based on the of signal analysis type wavelets is presented and how this technique can be used to predict transient and nonlinear phenomena. Once defined the method, its application in the identification of the friction of rotors is demonstrated. With this, one demonstrates that the method presented in this paper allows to also identifying in real time the rubbing phenomenon and also that it can be used as an of analysis technique in the preventive maintenance systems. [Spanish] Los procesos modernos de analisis de senales que miden vibraciones mecanicas se basan en la transformada rapida de Fourier (FFT por sus siglas en ingles), sin embargo, este metodo no es capaz de identificar fenomenos transitorios ni de naturaleza no lineal. A pesar de que se han hecho muchos esfuerzos para tratar de identificar estos fenomenos en los espectros de frecuencia, no es posible correlacionar el espectro con las caracteristicas fisicas de este tipo de fenomenos. Dentro de estos fenomenos sobre el rozamiento de un rotor contra la carcasa o munon de una chumacera, este fenomeno tiene un comportamiento no lineal, como se demuestra en este trabajo. En la primera parte se presenta un metodo basado en el analisis de senales tipo wavelets y como esta tecnica puede utilizarse para predecir fenomenos transitorios y no lineales. Una vez definido el metodo, se demuestra su

  11. Aloin Inhibits Interleukin (IL)-1β-Stimulated IL-8 Production in KB Cells.

    Science.gov (United States)

    Na, Hee Sam; Song, Yu Ri; Kim, Seyeon; Heo, Jun-Young; Chung, Hae-Young; Chung, Jin

    2016-06-01

    Interleukin (IL)-1β, which is elevated in oral diseases including gingivitis, stimulates epithelial cells to produce IL-8 and perpetuate inflammatory responses. This study investigates stimulatory effects of salivary IL-1β in IL-8 production and determines if aloin inhibits IL-1β-stimulated IL-8 production in epithelial cells. Saliva was collected from volunteers to determine IL-1β and IL-8 levels. Samples from volunteers were divided into two groups: those with low and those with high IL-1β levels. KB cells were stimulated with IL-1β or saliva with or without IL-1 receptor agonist or specific mitogen-activated protein kinase (MAPK) inhibitors. IL-8 production was measured by enzyme-linked immunosorbent assay (ELISA). MAPK protein expression involved in IL-1β-induced IL-8 secretion was detected by Western blot. KB cells were pretreated with aloin, and its effect on IL-1β-induced IL-8 production was examined by ELISA and Western blot analysis. Saliva with high IL-1β strongly stimulated IL-8 production in KB cells, and IL-1 receptor agonist significantly inhibited IL-8 production. Low IL-1β-containing saliva did not increase IL-8 production. IL-1β treatment of KB cells induced activation of MAPK signaling molecules as well as nuclear factor-kappa B. IL-1β-induced IL-8 production was decreased by p38 and extracellular signal-regulated kinase (ERK) inhibitor treatment. Aloin pretreatment inhibited IL-1β-induced IL-8 production in a dose-dependent manner and inhibited activation of the p38 and ERK signaling pathway. Finally, aloin pretreatment also inhibited saliva-induced IL-8 production. Results indicated that IL-1β in saliva stimulates epithelial cells to produce IL-8 and that aloin effectively inhibits salivary IL-1β-induced IL-8 production by mitigating the p38 and ERK pathway. Therefore, aloin may be a good candidate for modulating oral inflammatory diseases.

  12. A Novel Immunoregulatory Function for IL-23: Inhibition of IL-12 Dependent IFN-γ Production

    Science.gov (United States)

    Sieve, Amy N.; Meeks, Karen D.; Lee, Suheung; Berg, Rance E.

    2011-01-01

    Summary Most studies investigating the function of IL-23 have concluded that it promotes IL-17 secreting T cells. While some reports have also characterized IL-23 as having redundant pro-inflammatory effects with IL-12, we have instead found that IL-23 antagonizes IL-12 induced secretion of IFN-γ. When splenocytes or purified populations of T cells are cultured with IL-23, IFN-γ secretion in response to IL-12 is dramatically reduced. The impact of IL-23 is most prominent in CD8 T cells, but is also observed in NK and CD4 T cells. Mechanistically, the IL-23 receptor is not required for this phenomenon, and IL-23 inhibits signaling through the IL-12 receptor by reducing IL-12 induced signal transducer and activator of transcription 4 (STAT4) phosphorylation. IL-23 is also able to reduce IFN-γ secretion by antagonizing endogenously produced IL-12 from Listeria monocytogenes (LM) infected macrophages. In vivo, LM infection induces higher serum IFN-γ levels and a greater percentage of IFN-γ+CD8+ T cells in IL-23p19 deficient mice as compared to wild-type mice. This increase in IFN-γ production coincides with increased LM clearance at days 2–3 post-infection. Our data suggest that IL-23 may be a key factor in determining the responsiveness of lymphocytes to IL-12 and their subsequent secretion of IFN-γ. PMID:20458705

  13. Identification and Characterization of a Novel IL-4 Receptor α Chain (IL-4Rα Antagonist to Inhibit IL-4 Signalling

    Directory of Open Access Journals (Sweden)

    Nayyar Ahmed

    2015-05-01

    Full Text Available Background/Aims: In recent times, allergy has become a financial, physical and psychological burden to the society as a whole. In allergic cascades, cytokine IL-4 binds to IL-4 receptor (IL-4R, consequently producing allergen-specific IgE antibodies by B cells. In addition, among other functions, IL-4 is also responsible for B and T cell proliferation and differentiation. Hence, characterization of novel antagonists that inhibit IL-4 signalling forms the overall aim of this study. Methods: Phage display was used to screen a random 12-mer synthetic peptide library with a human IL-4Rα to identify peptide candidates. Once identified, the peptides were commercially synthesized and used for in vitro immunoassays. Results: We have successfully used phage display to identify M13 phage clones that demonstrated specific binding to IL-4Rα. The peptide N1 was synthesized for use in ELISA, demonstrating significant binding to IL-4Rα and inhibiting interaction with cytokine IL-4. Furthermore, the peptide was tested in a transfected HEK-Blue IL-4 reporter cell line model, which produces alkaline phosphatase (AP. QUANTI-Blue, a substrate, breaks down in the presence of AP producing a blue coloration. Using this colorimetric analysis, >50% inhibition of IL-4 signalling was achieved. Conclusion: We have successfully identified and characterised a synthetic peptide antagonist against IL-4Rα, which effectively inhibits IL-4 interaction with the IL-4Rα in vitro. Since IL-4 interaction with IL-4Rα is a common pathway for many allergies, a prophylactic treatment can be devised by inhibiting this interaction for future treatment of allergies.

  14. The role of IL-17 in psoriasis.

    Science.gov (United States)

    Malakouti, Mona; Brown, Gabrielle Elena; Wang, Eva; Koo, John; Levin, Ethan C

    2015-02-01

    Psoriasis is a chronic skin condition traditionally believed to involve the Th1 pathway. Recently, the IL-23/Th17/IL-17 pathway has been highlighted in the pathogenesis of psoriasis and other autoimmune inflammatory conditions. From a clinician's perspective, we sought to review the basic science data relevant to IL-17's role in psoriasis pathogenesis. We performed a Pubmed and Web of Knowledge search for English articles starting from 1990 that discussed the Th17 pathway. Search terms such as "IL-17" and "psoriasis" were utilized. The IL-17 pathway is regulated by IL-23, a cytokine that is vital for the expansion and maintenance of the Th17 cell population. Th17 derived cytokines (IL-17A, IL-17F, IL-17A/F and IL-22) were elevated in both psoriasis-like murine models and human psoriatic lesional biopsies. Ixekizumab (anti-IL-17A) treatment of psoriasis was found to normalize levels of IL-17 downstream gene products. Both preclinical and clinical studies support the central role of IL-17 in the pathogenesis of psoriasis.

  15. Hmgb1-IL-23-IL-17-IL-6-Stat3 Axis Promotes Tumor Growth in Murine Models of Melanoma

    Directory of Open Access Journals (Sweden)

    Qiu Tang

    2013-01-01

    Full Text Available In order to understand how tumor cells can escape immune surveillance mechanisms and thus develop antitumor therapies, it is critically important to investigate the mechanisms by which the immune system interacts with the tumor microenvironment. In our current study, IL-17 deficiency results in reduced melanoma tumor size, diminished numbers of proliferating cells and blood vessels, and decreased percentage of CD11b+Gr-1+ MDSCs in tumor tissues. IL-17 promotes IL-6 induction and Stat3 activation. Treatment of Stat3 inhibitor WP1066 in B16-F10 tumor cells inoculated wild-type mice inhibits tumor growth. Additional administration of recombinant IL-6 into B16-F10 tumor-bearing IL-17−/− mice results in markedly increased tumor size and p-Stat3 expression, whereas additional recombinant IL-17 administration into B16-F10 tumor-bearing wild-type mice treated with anti-IL-6 mAb does not significantly alter the tumor growth and p-Stat3 expression. In our further study, blockade of Hmgb1-RAGE pathway inhibits melanoma tumor growth and reduces production of IL-23 and IL-17. All these data suggest that Hmgb1-IL-23-IL-17-IL-6-Stat3 axis plays a pivotal role in tumor development in murine models of melanoma, and blocking any portion of this axis will attenuate melanoma tumor growth.

  16. IL RADIODRAMMA COME STRUMENTO DIDATTICO

    Directory of Open Access Journals (Sweden)

    Valeria Cattaneo

    2018-03-01

    Full Text Available Può un format apparentemente superato come il radiodramma rappresentare uno strumento didattico innovativo? In questo articolo viene presentato un progetto sperimentale in cui il format del dramma radiofonico è stato messo al servizio dell’insegnamento dell’italiano come lingua seconda. Dopo una breve rassegna delle peculiarità di questo “teatro senza palcoscenico”, se ne illustrano sommariamente la storia e le precedenti applicazioni in ambito scolastico-formativo. In seguito sono esposte la struttura, le tempistiche e gli strumenti di realizzazione, nonché le finalità didattiche complessive e quelle peculiari di ciascuna fase del progetto. Vengono quindi esplicitate le funzioni comunicative, le aree lessicali e le strutture morfosintattiche selezionate per portare a termine il task finale: la produzione di una puntata di radiodramma. Nella conclusione, nell’ottica di una possibile riproposta del progetto, si mettono in luce i punti di forza e le criticità emerse dalla sperimentazione attuata. In Appendice viene dato il copione del radiodramma in versione integrale, accompagnato da un collegamento ipertestuale per poter ascoltare il podcast prodotto dagli studenti.   Radio drama as a teaching tool Can an apparently old-fashioned format like a radio play be an innovative teaching tool? This article illustrates an experimental project where this format was used to teach Italian as a second language. After a brief overview of the peculiarities of this “stageless theatre”, a summary of its history and applications in schools and training contexts is presented. The structure of the radio play, the time and realization of the tools is explained, with the general didactic goals and the specific purpose of each stage of the project. The communicative functions, the lexical areas and the morpho-syntactic structures selected in order to create the final project – the production of a radio play – are summarized. In conclusion, we

  17. Screening criteria for ILs used in NH

    NARCIS (Netherlands)

    Wang, M.; Infante Ferreira, C.A.; Groll, Eckhard

    2016-01-01

    This paper describes a properties-optimization work for the working fluids in NH3 / ionic liquid (ILs) based single-effect absorption heat pumps. The optimum parameters of the IL can be used as criteria in screening task-specified ILs, which play the role of absorbents, in absorption heat pumps.

  18. Il Generale e il professore. Roma-Lubiana 1942

    OpenAIRE

    Sala, Teodoro

    2004-01-01

    Durante l'estate del 1942 l'XI Corpo d'armata scatenò la sua offensiva mettendo a ferro e fuoco la Slovenia annessa. Fungeva da vademecum la circolare di Roatta: esecuzioni sommarie anche collettive, incendio di centri abitati, deportazione di nuclei sempre più consistenti di civili, distruzione di opere pubbliche, requisizioni di bestiame e derrate, furono all'ordine del giorno. Impegnati nelle operazioni sessantamila soldati di quattro divisioni più complementi. Il comandante del Corpo d'ar...

  19. Cord Blood Cells Responses to IL2, IL7 and IL15 Cytokines for mTOR Expression

    Directory of Open Access Journals (Sweden)

    Anahita Mohammadian

    2017-04-01

    Full Text Available Purpose: Mammalian target of rapamycin (mTORis important in hematopoiesis and affect cell growth,differentiation and survival. Although previous studies were identified the effect of cytokines on the mononuclear cells development however the cytokines effect on mTOR in cord blood mononuclear cells was unclear. The aim of this study was to evaluate mTOR expression in cord blood mononuclear and cord blood stem cells (CD34+ cells in culture conditions for lymphoid cell development. Methods: Isolation of The mononuclear cells (MNCs from umbilical cord blood were done with use of Ficollpaque density gradient. We evaluated cultured cord blood mononuclear and CD34+ cells in presece of IL2, IL7 and IL15 at distinct time points during 21 days by using flow cytometry. In this study, we presented the role of IL2, IL7 and IL15 on the expression of mTOR in cord blood cells. Results: mTOR expression were increased in peresence of IL2, IL7 and IL15 in day 14 and afterword reduced. However in persence of IL2 and IL15 expression of mTOR significantly reduced. mTOR expression in CD34+ cells decreased significantly from day7 to day 21 in culture. Conclusion: cytokines play important role in mTOR expression during hematopoiesis and development of cord blood mononuclear cells.

  20. Il gioco le leggi naturali governano il caso

    CERN Document Server

    Eigen, Manfred

    1986-01-01

    Manfred Eigen, Premio Nobel per la chimica nel 1967, e la sua collaboratrice Ruthild Winkler hanno voluto con questo libro uscire allo scoperto, esponendo in una trattazione complessa ma comprensibile per ogni lettore veramente interessato una teoria molto audace, basata su ricerche e scoperte di Eigen stesso e di altri (come per esempio Thom e Prigogine) che in questi ultimi anni sono al centro dell’attenzione degli scienziati, anche se non sempre sono filtrate al di fuori della loro cerchia. Questa teoria ha come perno la nozione di gioco: e non già in una o più delle innumerevoli accezioni della parola, ma in tutte, con l’aggiunta di una ulteriore accezione che sottende tutte le altre: il gioco come struttura intelligibile emergente dal divenire caotico, quindi come fenomeno «che ha guidato fin dall’inizio il corso dell’Universo». Gioco, in questo libro, è dunque un «fenomeno naturale», non specificamente umano. I giochi che noi tutti giochiamo sono soltanto la schiuma variegata di un flutto...

  1. Structure of IL-22 Bound to Its High-Affinity IL-22R1 Chain

    Energy Technology Data Exchange (ETDEWEB)

    Jones, B.C.; Logsdon, N.J.; Walter, M.R. (UAB)

    2008-09-29

    IL-22 is an IL-10 family cytokine that initiates innate immune responses against bacterial pathogens and contributes to immune disease. IL-22 biological activity is initiated by binding to a cell-surface complex composed of IL-22R1 and IL-10R2 receptor chains and further regulated by interactions with a soluble binding protein, IL-22BP, which shares sequence similarity with an extracellular region of IL-22R1 (sIL-22R1). IL-22R1 also pairs with the IL-20R2 chain to induce IL-20 and IL-24 signaling. To define the molecular basis of these diverse interactions, we have determined the structure of the IL-22/sIL-22R1 complex. The structure, combined with homology modeling and surface plasmon resonance studies, defines the molecular basis for the distinct affinities and specificities of IL-22 and IL-10 receptor chains that regulate cellular targeting and signal transduction to elicit effective immune responses.

  2. Differential regulation of human IL-7 receptor alpha expression by IL-7 and TCR signaling

    NARCIS (Netherlands)

    Alves, Nuno L.; van Leeuwen, Ester M. M.; Derks, Ingrid A. M.; van Lier, René A. W.

    2008-01-01

    IL-7Ralpha is essential for the development and homeostatic maintenance of mature T cells. Studies in humans and mice have shown that IL-7Ralpha expression is reduced by its cognate cytokine, IL-7, and Ag, suggesting that active regulation of IL-7 responsiveness is necessary to balance T cell

  3. Role of interleukin-23 (IL-23) receptor signaling for IL-17 responses in human Lyme disease

    NARCIS (Netherlands)

    Oosting, M.; Hofstede, H.J.M. ter; Veerdonk, F.L. van de; Sturm, P.D.J.; Kullberg, B.J.; Meer, J.W.M. van der; Netea, M.G.; Joosten, L.A.B.

    2011-01-01

    Interleukin-23 (IL-23) is known to play a crucial role in the development and maintenance of T helper 17 cells. It has been previously demonstrated that IL-17 is involved in experimental Lyme arthritis, caused by Borrelia burgdorferi bacteria. However, the precise role of the IL-23 receptor (IL-23R)

  4. Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation

    DEFF Research Database (Denmark)

    Galle, Pia; Jensen, Lene; Andersson, Christina

    2007-01-01

    IL-6 is involved in inflammation and a therapeutic target. 0.1% of Danish blood donors have nanomolar plasma concentrations of polyclonal, picomolar affinity and in vitro as well as in vivo neutralizing IgG autoantibodies to IL-6 (aAb-IL-6). Such donors are assumed to be severely IL-6 deficient; ...... principle might be a viable alternative in immune competent humans suffering from disorders driven by IL-6....

  5. Clinical value of determination of changes of serum Gas, IL-2, IL-10 and IL-18 levels after transfusion of Red blood cells in patients with peptic ulcer

    International Nuclear Information System (INIS)

    Liu Tingting; Li Xinghua

    2011-01-01

    Objective: To investigation the changes of serum Gas, IL-2, IL-10 and IL-18 contents after transfusion of red blood cells in patients with peptic ulcer. Methods: Serum Gas, IL-2, IL-10 (with RIA), serum IL-18 (with ELISA) levels were measured in 31 patients with peptic ulcer and 35 controls. Results: Before transfusion,the serum IL-2 level in the patients was significantly lower than that in controls (P 0.05). Conclusion: Detection of serum Gas, IL-2, IL-10 and IL-18 levels is clinically useful for monitoring progress and favourable prognosis of patients with peptic ulcer possess important clinical value. (authors)

  6. IL-6, in synergy with IL-7 or IL-15, stimulates TCR-independent proliferation and functional differentiation of CD8+ T lymphocytes.

    Science.gov (United States)

    Gagnon, Julien; Ramanathan, Sheela; Leblanc, Chantal; Cloutier, Alexandre; McDonald, Patrick P; Ilangumaran, Subburaj

    2008-06-15

    Recent reports have shown that IL-21, in synergy with IL-15, stimulates proliferation of CD8(+) T lymphocytes in the absence of signaling via the TCR. In this study, we show that IL-6, which induces phosphorylation of STAT3 similarly to IL-21, also can stimulate proliferation of CD8(+) T cells in synergy with IL-7 or IL-15. IL-6 displays a stronger synergy with IL-7 than with IL-15 to stimulate naive CD8(+) T cells. Concomitant stimulation by IL-6 or IL-21 augments phosphorylation and DNA-binding activity of STAT5 induced by IL-7 or IL-15. Like IL-21, IL-6 reduces the TCR signaling threshold required to stimulate CD8(+) T cells. Prior culture of P14 TCR transgenic CD8 T cells with IL-6 or IL-21 in the presence of IL-7 or IL-15 augments their proliferation and cytolytic activity upon subsequent stimulation by Ag. Furthermore, cytokine stimulation induces quantitatively and qualitatively distinct phenotypic changes on CD8(+) T cells compared with those induced by TCR signaling. We propose that the ability of IL-6 to induce TCR-independent activation of CD8(+) T cells in synergy with IL-7 or IL-15 may play an important role in the transition from innate to adaptive immunity.

  7. INSEGNARE LETTERATURA ATTRAVERSO IL GLOTTODRAMA A STUDENTI DI ITALIANO LS/L2

    Directory of Open Access Journals (Sweden)

    Antonietta Gobbis

    2016-02-01

    Full Text Available In occasione del 750° anniversario della nascita di Dante Alighieri gli studenti dell’Università delle Lingue Mondiali di Tashkent (Uzbekistan hanno dedicato uno spettacolo alla “Divina Commedia”. Questo progetto, una performance musicale-teatrale, è stato presentato presso la Libreria Statale Alisher Navoi durante la XV Settimana della Lingua Italiana nel  Mondodal titolo “L’Italiano della musica, la musica dell’Italiano”.Insegnare la Letteratura attraverso il teatro è stata un’esperienza molto soddisfacente perché abbiamo potuto constatare negli studenti un sensibile miglioramento della competenza comunicativa orale, della creatività e della fiducia in sé stessi. Essa si è basata su principi didattici derivati dal teatro di Strasberg, Brecht, Boal e sul Glottodrama, un’innovativa metodologia che intende combinare l’approccio comunicativo alle tecniche e strategie drammatiche nell’apprendimento delle lingue straniere. Fulcro di questo metodo è la struttura dell’unità didattica: la sequenza performance-riflessione-performance sostituisce quella consueta di riflessione-performance-riflessione permettendo all’apprendente l’immediata identificazione nel personaggio attraverso il role-playing ed una migliore comprensione delle situazioni. Teaching Italian Literature through GlottodramaOn occasion of the 750th anniversary of the birth of Dante Alighieri, students at the University of World Languages in Tashkent dedicated a performance of the “Divina Commedia” to the author. The project, that brought together music and theatre, was presented at the Uzbek Alisher Navoiin State Library during the XV World Italian Language Week entitled “The Italian of Music, the Music of Italian”.Teaching literature through drama was a very successful experience because students were able to improve their fluency, creativity and self-confidence in speaking considerably. The project was based on the didactic principles of

  8. Expression of IL33 and IL35 in oral lichen planus.

    Science.gov (United States)

    Javvadi, L R; Parachuru, V P B; Milne, T J; Seymour, G J; Rich, Alison M

    2018-04-09

    Oral lichen planus (OLP) is a complex immunological disorder, mediated in part by the release of cytokines by activated T-cells. Recently, the role of novel cytokines including IL33 and IL35 has been described in various chronic inflammatory diseases. IL33, a member of the IL-1 superfamily of cytokines, functions as an 'alarmin' released after cell necrosis to alert the immune system to tissue damage or stress. IL35, a member of IL12 cytokine family, is produced by regulatory T-cells and suppresses the immune response. The expression of IL33 and IL35 is yet to be investigated in OLP. The aim of this study was to determine the presence and topographical distribution of IL33 and IL35 in OLP using immunohistochemistry and quantitative real-time reverse transcriptase polymerase chain reaction (qPCR). For IHC, formalin-fixed paraffin-embedded archival specimens of OLP (n = 10) and a non-specific inflammatory (NSI) control group (n = 9) were used. A double-labelling immunofluorescence technique was used to determine the expression of IL33 and IL35 on CD3 + T-cells. In addition, 12 fresh tissue samples (OLP n = 6 and NSI controls n = 6) were used to determine the gene expression of IL33 and EBI3 (one chain of the dimeric IL35). Quantitative and qualitative analysis was performed with statistical significance set at p < 0.05. IHC showed positive immunostaining with IL33 and IL35 in both OLP and NSI. Comparison of the numbers of IL33 + and IL35 + cells in OLP and NSI did not show any significant difference. In OLP, there were significantly more IL33 + cells in the deeper connective tissue region than at the epithelial-connective tissue interface. Interestingly, all IL35 + cells observed in both OLP and NSI tissues showed ovoid/plasmacytoid morphology. Double-labelling immunofluorescence showed that IL33 and IL35 expression was not localized within CD3 + T-cells. The gene expression experiments showed significantly higher expression of EBI3 (fold

  9. Expanding Diversity in Molecular Structures and Functions of the IL-6/IL-12 Heterodimeric Cytokine Family

    Directory of Open Access Journals (Sweden)

    Hideaki Hasegawa

    2016-11-01

    Full Text Available The interleukin (IL-6/IL-12 family cytokines have pleiotropic functions and play critical roles in multiple immune responses. This cytokine family has very unique characteristics in that they are composed of two distinct subunits forming a heterodimer and each cytokine and receptor subunit shares with each other. The members of this cytokine family are increasing; currently, there are more than 6 cytokines, including the tentatively named cytokines IL-Y (p28/p40, IL-12 (p35/p40, IL-23 (p19/p40, IL-27 p28/Epstein-Barr virus-induced protein 3 (EBI3, IL-35 (p35/EBI3, and IL-39 (p19/EBI3. This family of cytokines covers a very broad range of immune responses, including pro-inflammatory responses such as helper T (Th1, Th2, and Th17 to anti-inflammatory responses such as regulatory T (Treg cells and IL-10-producing Treg cells. IL-12 is the first member of this family, and IL-12, IL-23, and IL-27 are mainly produced by activated antigen-presenting cells such as dendritic cells and macrophages. IL-12 plays a critical role in the promotion of Th1 immune responses by inducing interferon-γ production to combat pathogens and malignant tumors. IL-23 induces IL-17 production and is necessary to maintain pathogenic Th17 cells that cause inflammatory and autoimmune diseases. IL-27 was initially reported to play a critical role in promotion of Th1 differentiation; however, subsequent studies revealed that IL-27 has broader stimulatory and inhibitory roles by inducing IL-10-producing Treg cells. IL-35 is produced by forkhead box P3+ Treg cells and activated B cells and has immunosuppressive functions to maintain immune tolerance. The most recently identified cytokine, IL-39, is produced by activated B cells and has pro-inflammatory functions. The cytokine tentatively named IL-Y seems to have anti-inflammatory functions by inhibiting Th1 and Th17 differentiation. In addition, individual cytokine subunits were also shown to have self-standing activities. Thus

  10. FOTOGRAFIA DI STRUMENTI MUSICALI METODO DI DOCUMENTAZIONE QUOTIDIANO E PROVE ELEMENTARI DI FILOLOGIA DIGITALE

    Directory of Open Access Journals (Sweden)

    Emanuele Marconi

    2012-04-01

    Full Text Available

    Il restauro virtuale, inteso come manipolazione 2d di un’immagine attraversoprogrammi di grafi ca o elaborazione digitale, può essere, in alcuni casi, unvalido aiuto per la ricerca ontologica per ottenere una visione di insieme diun'opera prima di un intervento di restauro o per ricostruire parti che non sonopervenute. In alcuni casi la manipolazione dell’immagine diviene un supporto perla ricerca organologica.

     

    Digital photo of musical instruments

    Digital photography is a great support in musical instruments conservation forms filling. Video documentation, still not much used, contributes a great amount of details that doesn’t written text or still images. Digital image manipulation,or virtual restoration (defined as the manipulation of 2D image through digital imaging processing, in some cases can be a great help to get a fi rst overview of a restoration, or to reconstruct parts of an artwork that are missed. Some case studies are presented, showing differents application ofsimple techniques to on the field activities regarding musical instruments.

  11. IL-21 Receptor Expression in Human Tendinopathy

    Science.gov (United States)

    Campbell, Abigail L.; Smith, Nicola C.; Reilly, James H.; Kerr, Shauna C.; Leach, William J.; Fazzi, Umberto G.; Rooney, Brian P.; Murrell, George A. C.; Millar, Neal L.

    2014-01-01

    The pathogenetic mechanisms underlying tendinopathy remain unclear, with much debate as to whether inflammation or degradation has the prominent role. Increasing evidence points toward an early inflammatory infiltrate and associated inflammatory cytokine production in human and animal models of tendon disease. The IL-21/IL-21R axis is a proinflammatory cytokine complex that has been associated with chronic inflammatory diseases including rheumatoid arthritis and inflammatory bowel disease. This project aimed to investigate the role and expression of the cytokine/receptor pair IL-21/IL-21R in human tendinopathy. We found significantly elevated expression of IL-21 receptor message and protein in human tendon samples but found no convincing evidence of the presence of IL-21 at message or protein level. The level of expression of IL-21R message/protein in human tenocytes was significantly upregulated by proinflammatory cytokines (TNFα/IL-1β) in vitro. These findings demonstrate that IL-21R is present in early human tendinopathy mainly expressed by tenocytes and macrophages. Despite a lack of IL-21 expression, these data again suggest that early tendinopathy has an inflammatory/cytokine phenotype, which may provide novel translational targets in the treatment of tendinopathy. PMID:24757284

  12. IL-21 Receptor Expression in Human Tendinopathy

    Directory of Open Access Journals (Sweden)

    Abigail L. Campbell

    2014-01-01

    Full Text Available The pathogenetic mechanisms underlying tendinopathy remain unclear, with much debate as to whether inflammation or degradation has the prominent role. Increasing evidence points toward an early inflammatory infiltrate and associated inflammatory cytokine production in human and animal models of tendon disease. The IL-21/IL-21R axis is a proinflammatory cytokine complex that has been associated with chronic inflammatory diseases including rheumatoid arthritis and inflammatory bowel disease. This project aimed to investigate the role and expression of the cytokine/receptor pair IL-21/IL-21R in human tendinopathy. We found significantly elevated expression of IL-21 receptor message and protein in human tendon samples but found no convincing evidence of the presence of IL-21 at message or protein level. The level of expression of IL-21R message/protein in human tenocytes was significantly upregulated by proinflammatory cytokines (TNFα/IL-1β in vitro. These findings demonstrate that IL-21R is present in early human tendinopathy mainly expressed by tenocytes and macrophages. Despite a lack of IL-21 expression, these data again suggest that early tendinopathy has an inflammatory/cytokine phenotype, which may provide novel translational targets in the treatment of tendinopathy.

  13. Il Gambling Compulsivo: rilevanza epidemiologica

    Directory of Open Access Journals (Sweden)

    A. Coacci

    2003-05-01

    Full Text Available

    Introduzione: il gioco d’azzardo ha profonde radici nella storia e nella cultura di ogni popolo. Si stima che circa l’80% della popolazione adulta nel nostro Paese giochi d’azzardo. Esso, pur rappresentando per la maggior parte di queste persone solo un innocuo passatempo, si trasforma talora in una vera e propria malattia (gambling compulsivo, con comportamenti che denotano forme estreme di rischio, sino a forme che portano alla distruzione della famiglia e persino della propria vita.

    Si tratta un disturbo poco conosciuto e spesso non diagnosticato. Infatti, benché sia largamente diffuso e comporti rilevanti costi umani e sociali, il gambling compulsivo solo di recente è stato incluso nelle classificazioni diagnostiche internazionali.

    Obiettivi: valutare l’impatto epidemiologico del gambling compulsivo (gioco d’azzardo patologico in una ASL/provincia.

    Materiali e metodi: è stato inviato un questionario ai 190 Medici di Medicina Generale della provincia di Grosseto (ASL 8, per raccogliere informazioni su: sistema di cura, numero di soggetti che si sono rivolti al proprio medico di famiglia per tale problema, eventuale coesistenza di problemi e comportamenti di dipendenza e di abuso (alcool, psicofarmaci, droghe illegali, ecc.

    Risultati: sono pervenuti 127 (pari al 66,8% questionari compilati. L’elaborazione dei dati è tuttora in corso.

    Conclusioni: dai risultati preliminari sembra emergere che il numero di persone che chiede aiuto al medico e al SSN, differentemente da quanto accade per i tossicodipendenti, è molto limitato e, quindi, intuitivamente poco indicativo della massa di soggetti realmente coinvolti dalla problematica studiata. Si discute del ruolo nella promozione della salute potenzialmente svolto dai Medici di Medicina Generale. Per quanto la tecnica di rilevazione appaia relativamente poco sensibile

  14. IL-15 and IL-17F are differentially regulated and expressed in mycosis fungoides (MF)

    DEFF Research Database (Denmark)

    Willerslev-Olsen, Andreas; Litvinov, Ivan V; Fredholm, Simon M

    2014-01-01

    Skin lesions from mycosis fungoides (MF) patients display an increased expression of interleukin-15 (IL-15), IL-17F, and other cytokines implicated in inflammation and malignant cell proliferation in cutaneous T-cell lymphoma (CTCL). In the leukemic variant of CTCL, Sézary syndrome (SS), IL-2...... and IL-15 trigger activation of the Jak-3/STAT3 pathway and transcription of IL17A gene, whereas it is unknown what causes IL-15 expression, Jak3/STAT3 activation, and production of IL-17F in MF. Here, we studied the expression and regulation of IL-15 and its relation to IL-17F in MF cell lines and skin......-malignant MF T cells, whereas the spontaneous STAT3 activation and IL-17F expression in malignant T cells is not inhibited; (3) patients display heterogeneous IL-15/IL-17F mRNA expression patterns in skin lesions; and (4) IL-15 expression (in contrast to IL-17F) is not associated with progressive disease...

  15. 25-Hydroxyvitamin D, IL-31, and IL-33 in Children with Allergic Disease of the Airways

    Directory of Open Access Journals (Sweden)

    Anna Bonanno

    2014-01-01

    Full Text Available Low vitamin D is involved in allergic asthma and rhinitis. IL-31 and IL-33 correlate with Th2-associated cytokines in allergic disease. We investigated whether low vitamin D is linked with circulating IL-31 and IL-33 in children with allergic disease of the airways. 25-Hydroxyvitamin D [25(OH Vit D], IL-31, and IL-33 plasma levels were measured in 28 controls (HC, 11 allergic rhinitis (AR patients, and 35 allergic asthma with rhinitis (AAR patients. We found significant lower levels of 25(OH Vit D in AR and in AAR than in HC. IL-31 and IL-33 plasma levels significantly increased in AAR than HC. IL-31 and IL-33 positively correlated in AR and AAR. 25(OH Vit D deficient AAR had higher levels of blood eosinophils, exacerbations, disease duration, and total IgE than patients with insufficient or sufficient 25(OH Vit D. In AAR 25(OH Vit D levels inversely correlated with total allergen sIgE score and total atopy index. IL-31 and IL-33 did not correlate with 25(OH Vit D in AR and AAR. In conclusion, low levels of 25(OH Vit D might represent a risk factor for the development of concomitant asthma and rhinitis in children with allergic disease of the airways independently of IL-31/IL-33 Th2 activity.

  16. IL-28 and IL-29 as protective markers in subject with dengue fever.

    Science.gov (United States)

    Hung, Chih-Hsing; Huang, Chung-Hao; Wang, Lin; Huang, Chun-Chi; Wu, Meng-Chieh; Chin, Yi-Ying; Lin, Chun-Yu; Chang, Ko; Wu, Deng-Chyang; Chen, Yen-Hsu

    2017-06-01

    About 400 million people every year are estimated to contract dengue virus infection, which causes prolonged morbidity and sometimes mortality. Interleukin (IL)-28 and IL-29 are relatively newly discovered cytokines and play an important role in our immune defense against pathogens, especially for viral infection. In the present study, we investigated serum IL-28 and IL-29 expression and the relationship to clinical and laboratory parameters in patients with dengue virus infection. Adult patients with dengue (n = 45) and control group (n = 24) were included prospectively. Clinical symptoms and laboratory data were collected from every patient. We investigated IL-28 and IL-29 levels in serum by ELISA. The concentrations of serum IL-28 and IL-29 were significantly higher in subjects with dengue when compared to those of control group. The patients with higher serum IL-28 and IL-29 levels had significantly lower ALAT and peripheral blood neutrophil percentage, but higher peripheral platelet, total white blood cell (WBC), monocyte, and lymphocyte counts. Patients with higher serum IL-28 and IL-29 levels also had more flu-like symptoms, but less vomiting. Increased level of IL-28 and IL-29 was associated with better liver function, platelet and WBC numbers and clinical symptom in subjects with dengue and could potentially serve as a protective marker.

  17. IL-36γ Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis

    Directory of Open Access Journals (Sweden)

    Charlie Bridgewood

    2018-02-01

    Full Text Available The IL-1 family member cytokine IL-36γ is recognised as key mediator in the immunopathology of psoriasis, hallmarks of which involve the activation of both resident and infiltrating inflammatory myeloid cells and aberrant angiogenesis. This research demonstrates a role for IL-36γ in both myeloid activation and angiogenesis. We show that IL-36γ induces the production of psoriasis-associated cytokines from macrophages (IL-23 and TNFα and that this response is enhanced in macrophages from psoriasis patients. This effect is specific for IL-36γ and could not be mimicked by other IL-1 family cytokines such as IL-1α. IL-36γ was also demonstrated to induce endothelial tube formation and branching, in a VEGF-A-dependent manner. Furthermore, IL-36γ-stimulated macrophages potently activated endothelial cells and led to increased adherence of monocytes, effects that were markedly more pronounced for psoriatic macrophages. Interestingly, regardless of stimulus, psoriasis monocytes showed increased adherence to both the stimulated and unstimulated endothelium when compared with monocytes from healthy individuals. Collectively, these findings show that IL-36γ has the potential to enhance endothelium directed leucocyte infiltration into the skin and strengthen the IL-23/IL-17 pathway adding to the growing evidence of pathogenetic roles for IL-36γ in psoriatic responses. Our findings also point to a cellular response, which could potentially explain cardiovascular comorbidities in psoriasis in the form of endothelial activation and increased monocyte adherence.

  18. IL-36γ Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis.

    Science.gov (United States)

    Bridgewood, Charlie; Fearnley, Gareth W; Berekmeri, Anna; Laws, Philip; Macleod, Tom; Ponnambalam, Sreenivasan; Stacey, Martin; Graham, Anne; Wittmann, Miriam

    2018-01-01

    The IL-1 family member cytokine IL-36γ is recognised as key mediator in the immunopathology of psoriasis, hallmarks of which involve the activation of both resident and infiltrating inflammatory myeloid cells and aberrant angiogenesis. This research demonstrates a role for IL-36γ in both myeloid activation and angiogenesis. We show that IL-36γ induces the production of psoriasis-associated cytokines from macrophages (IL-23 and TNFα) and that this response is enhanced in macrophages from psoriasis patients. This effect is specific for IL-36γ and could not be mimicked by other IL-1 family cytokines such as IL-1α. IL-36γ was also demonstrated to induce endothelial tube formation and branching, in a VEGF-A-dependent manner. Furthermore, IL-36γ-stimulated macrophages potently activated endothelial cells and led to increased adherence of monocytes, effects that were markedly more pronounced for psoriatic macrophages. Interestingly, regardless of stimulus, psoriasis monocytes showed increased adherence to both the stimulated and unstimulated endothelium when compared with monocytes from healthy individuals. Collectively, these findings show that IL-36γ has the potential to enhance endothelium directed leucocyte infiltration into the skin and strengthen the IL-23/IL-17 pathway adding to the growing evidence of pathogenetic roles for IL-36γ in psoriatic responses. Our findings also point to a cellular response, which could potentially explain cardiovascular comorbidities in psoriasis in the form of endothelial activation and increased monocyte adherence.

  19. IL-4 Inhibits IL-1β-Induced Depressive-Like Behavior and Central Neurotransmitter Alterations

    Directory of Open Access Journals (Sweden)

    Hyun-Jung Park

    2015-01-01

    Full Text Available It has been known that activation of the central innate immune system or exposure to stress can disrupt balance of anti-/proinflammatory cytokines. The aim of the present study was to investigate the role of pro- and anti-inflammatory cytokines in the modulation of depressive-like behaviors, the hormonal and neurotransmitter systems in rats. We investigated whether centrally administered IL-1β is associated with activation of CNS inflammatory pathways and behavioral changes and whether treatment with IL-4 could modulate IL-1β-induced depressive-like behaviors and central neurotransmitter systems. Infusion of IL-4 significantly decreased IL-1β-induced anhedonic responses and increased social exploration and total activity. Treatment with IL-4 markedly blocked IL-1β-induced increase in PGE2 and CORT levels. Also, IL-4 reduced IL-1β-induced 5-HT levels by inhibiting tryptophan hydroxylase (TPH mRNA and activating serotonin transporter (SERT in the hippocampus, and levels of NE were increased by activating tyrosine hydroxylase (TH mRNA expression. These results demonstrate that IL-4 may locally contribute to the regulation of noradrenergic and serotonergic neurotransmission and may inhibit IL-1β-induced behavioral and immunological changes. The present results suggest that IL-4 modulates IL-1β-induced depressive behavior by inhibiting IL-1β-induced central glial activation and neurotransmitter alterations. IL-4 reduced central and systemic mediatory inflammatory activation, as well as reversing the IL-1β-induced alterations in neurotransmitter levels. The present findings contribute a biochemical pathway regulated by IL-4 that may have therapeutic utility for treatment of IL-1β-induced depressive behavior and neuroinflammation which warrants further study.

  20. Autophagy and IL-1 family cytokines

    Directory of Open Access Journals (Sweden)

    James eHarris

    2013-04-01

    Full Text Available Autophagy is an important intracellular homeostatic mechanism for the targeting of cytosolic constituents, including organelles, for lysosomal degradation. Autophagy plays roles in numerous physiological processes, including immune cell responses to endogenous and exogenous pathogenic stimuli. Moreover, autophagy has a potentially pivotal role to play in the regulation of inflammatory responses. In particular, autophagy regulates endogenous inflammasome activators, as well as inflammasome components and pro-IL-1β. As a result, autophagy acts a key modulator of IL-1β and IL-18, as well as IL-1α, release. This review focuses specifically on the role autophagy plays in regulating the production, processing and secretion of IL-1 and IL-18 and the consequences of this important function.

  1. Increased IL-20 and IL-24 target osteoblasts and synovial monocytes in spondyloarthritis

    DEFF Research Database (Denmark)

    Kragstrup, Tue Wenzel; Andersen, Morten Nørgaard; Schiøttz-Christensen, Berit

    2017-01-01

    The pathogenesis of spondyloarthritis (SpA) involves activation of the innate immune system, inflammation and new bone formation. The two cytokines interleukin (IL)-20 and IL-24 have been shown to link innate immune activation and tissue homeostasis. We hypothesized that these two cytokines...... are secreted as part of activation of the innate immune system and affect bone homeostasis in SpA. IL-20 and IL-24 were measured in plasma from axial SpA patients (n = 83). Peripheral SpA patients (n = 16) were included for in-vitro cell culture studies. The plasma IL-20 and IL-24 levels were increased in Sp...

  2. Roles of elevated intravitreal IL-1β and IL-10 levels in proliferative diabetic retinopathy

    OpenAIRE

    Mao, Chunjie; Yan, Hua

    2014-01-01

    Purpose: To determine the roles of interleukin (IL)-1β and IL-10 in the vitreous of proliferative diabetic retinopathy (PDR). Materials and Methods: Vitreous samples were obtained from 26 eyes of 26 patients with PDR and from eight eyes of eight cases without PDR. The IL-1β and IL-10 concentration in the vitreous was measured by using an enzyme-linked immunosorbent assay (ELISA). Results: Levels of IL-1β and IL-10 in vitreous were higher in PDR patients compared with control group. And there ...

  3. The role of CD40L, IL-10 and IL-17 in radioprotection

    International Nuclear Information System (INIS)

    Li Ting

    2003-01-01

    CD40L/CD40 interaction is central to the control of thymus-dependent humoral immunity and cell mediated immune responses. IL-17 has been shown to induce the production of IL-6 and G-CSF, which can induce proliferation and differentiation of CD34 + hematopoietic progenitors. IL-10 can interfere with up-regulation of costimulatory molecules, thus suppressing the production of costimulatory cytokines, such as IL-12. IL-10 has been implicated as an essential mediator in the induction of systemic immune suppression following ultraviolet (UV) exposure. Treating UV-irradiated mice with anti-IL-10 blocks the induction of immune suppression

  4. Dalla riqualificazione energetica al recupero sostenibile. Un metodo di analisi energetica dei tessuti della città compatta

    Directory of Open Access Journals (Sweden)

    Carlo Cecere

    2012-12-01

    Full Text Available A dispetto della sempre maggiore “insostenibilità” della città odierna, recenti statistiche ne hanno confermato il crescente potere attrattivo; una circostanza che vede il continente europeo presentare un’assoluta prevalenza del costruito esistente sul nuovo. Per tentare di raggiungere quel complesso stato di equilibrio, che in molti fanno ricadere sotto il nome di sostenibilità, appare dunque necessario confrontarsi con il patrimonio edilizio dei tessuti storici, piuttosto che realizzarne di nuovi ad alta efficienza. Si presentano qui i risultati di uno studio comparativo condotto su diversi tessuti urbani alla ricerca di relazioni tra densità urbana e performance energetiche. Tale metodologia può rappresentare una base di conoscenza che conduca a trasformazioni consapevoli verso condizioni a maggiore efficienza.

  5. Il fuoco della fusione termonucleare controllata

    CERN Document Server

    Caldirola, Piero; Sindoni, Elio

    1984-01-01

    Per realizzare la fusione termonucleare controllata, cioè catturare e dominare il fuoco che accende gli astri, e ottenere così una nuova fonte di energia praticamente illimitata e a basso costo, si richiede uno sforzo collettivo e unitario globale: non esiste infatti nazione al mondo che sia in grado, singolarmente presa, di affrontare il problema, sia per le risorse finanziarie necessarie all'impresa sia per il numero dei ricercatori che dovranno dedicarvisi.

  6. Il welfare aziendale nella crisi dello Stato

    OpenAIRE

    Caracciolo di Melissano, Francesco Pio

    2016-01-01

    La crisi economica iniziata nel 2007, da un lato ha determinato il sorgere di nuove e diversificate esigenze dei lavoratori, dall’altro ha indotto gli Stati a ridurre le risorse destinate al welfare. In questo contesto, le iniziative di welfare dei privati, racchiuse sotto la denominazione “welfare aziendale o di secondo livello”, hanno assunto un ruolo determinante nel garantire il benessere sociale ed in particolare quello dei lavoratori e delle loro famiglie. Il legislatore, da ultimo con ...

  7. Il viaggio gastronomico di Paolo Monelli.

    OpenAIRE

    Salarelli, Alberto

    2013-01-01

    Il ghiottone errante di Paolo Monelli, pubblicato nel 1935, rappresenta uno dei primi esempi di narrativa di viaggio in tema di enogastronomia, un genere destinato a grande successo nel secondo dopoguerra. In questo articolo, oltre a ripercorrere la vicenda biografica di Monelli, si sottolineano le relazioni tra Il ghiottone e la cultura gastronomica del regime fascista, e si evidenziano alcuni tratti caratteristici del suo stile di scrittura. Paolo Monelli‟s Il ghiottone errante (The Wand...

  8. IL-1 family members IL-18 and IL-33 upregulate the inflammatory potential of differentiated human Th1 and Th2 cultures

    DEFF Research Database (Denmark)

    Blom, Lars; Poulsen, Lars K.

    2012-01-01

    The IL-1 family members IL-1ß, IL-18, and IL-33 are potent cytokines in relationship to amplifying the CD4(+) T cell cytokine production. To evaluate their impact on in vitro-differentiated human Th1 and Th2 cultures, such cultures were established from naive T cells, purified from healthy blood...... donors, and reactivated in the presence of IL-1ß, IL-18, or IL-33. Interestingly, we observe modifying responses in Th1 and Th2 cultures induced by IL-18 or IL-33 but not by IL-1ß, both contributing to amplify production of IL-5, IL-13, and IFN-¿. IL-18 or IL-33 stimulation of Th1 cultures resulted...... in increased IFN-¿ and IL-13 production concurrent with reduced IL-10 gene transcription and secretion even though Th1 cultures, in contrast to IL-18Ra, had low ST2L expression. Furthermore, adding IL-18 to Th1 cultures promoted Tbet mRNA expression and production. Th2 cultures stimulated with IL-18 or IL-33...

  9. Sinergetica il segreto del successo della natura

    CERN Document Server

    Haken, Hermann

    1983-01-01

    Introduzione e sommario ; il disordine cresce sempre? la morte termica dell'universo ; i cristalli : strutture ordinate, ma morte ; strutture ordinate nei liquidi e nelle nubi e formazioni geologiche ; fiat lux! la luce del laser ; configurazioni chimiche ; l'evoluzione biologica e la sopravvivenza del migliore ; sopravvivi anche senza essere il migliore : specializzati, scavati una nicchia ecologica ; come si formano gli organismi biologici ; talvolta i conflitti sono ineluttabili ; il caos, il caso e la concezione meccanicistica del mondo ; gli effetti sinergetici nell'economia ; si possono prevedere le rivoluzioni ? ; le allucinazioni comprovano le teorie sul cervello.

  10. Il caso Lautsi contro l’Italia

    Directory of Open Access Journals (Sweden)

    Grégor Puppinck

    2012-02-01

    SOMMARIO: 1. Premesse – 2. Il ragionamento della Seconda Sezione - 2.1. La ridefinizione dalla finalità del sistema educativo pubblico - 2.2. Il pluralismo educativo come finalità – 2.3. Sintesi del ragionamento della Sezione – 2.4.  Una sentenza contestata - 3.  Il ragionamento sviluppato dalla Grande Camera - 3.1. La sussidiarietà e il margine di apprezzamento – 3.2.  Il laicismo è una convinzione filosofica non neutra – 3.3. La neutralità si applica all’ “agire” e non all' "essere” dello  Stato – 3.4.  Democrazia, neutralità confessionale e laicità – 3.5.  L’educazione pubblica  nel senso della Grande Camera – 3.6.  Il crocefisso: un simbolo passivo – 3.7.  L’assenza d’ingerenza dello Stato - 4.  Gli sviluppi supplementari alla sentenza della Grande Camera – 4.1.  Il crocefisso e il velo islamico – 4.2.  La libertà negativa di religione dei non credenti – 4.3. La falsa soluzione bavarese – 4.4.  La tradizione – 4.5. La religione maggioritaria – 4.6.  Il dibattito religioso e politico – 4.7. Le conseguenze del caso Lautsi.

  11. A reverse method to estimate initial temperatures in geothermal reservoirs; Un metodo inverso para estimacion de la temperatura inicial de yacimientos geotermicos

    Energy Technology Data Exchange (ETDEWEB)

    Garcia Gutierrez, Alfonso [Instituto de Investigaciones Electricas, Gerencia de Geotermia, Cuernavaca, Morelos (Mexico)]. E-mail: aggarcia@iie.org.mx; Ramos Alcantara, Jose R. [Centro Nacional de Investigacion y Desarrollo Tecnologico, Departamento de Ingenieria Mecanica, Cuernavaca, Morelos (Mexico); Arellano Gomez, Victor M. [Instituto de Investigaciones Electricas, Gerencia de Geotermia, Cuernavaca, Morelos (Mexico)

    2010-01-15

    A method is presented for estimating the initial temperature in geothermal-reservoir formations. The method is based on control theory where the measured temperatures or temperature logs are compared with corresponding simulated temperatures for different times with the well closed. The comparison is made using a control algorithm that makes changes to the originally assumed reservoir temperatures and performs iterations until the best fit between the temperature logs and the simulated temperatures is obtained. The simulation of fluid transport and heat in the well includes the processes of circulation and stop in the presence of circulation losses, modeled on macroscopic balances of momentum and energy. The transport processes in the formation regard the reservoir as an isotropic porous medium and fluid flow is described by Darcy's law. This model generates the fields of temperatures, pressures and speeds as a function of time and space. The method was tested with data from well LV-3 in Las Tres Virgenes geothermal field, Baja California Sur, Mexico. The estimated temperatures of the undisturbed formation-or initial temperatures-are compared within {+-}15 degrees Celsius with the measured temperatures, which is an acceptable outcome from an engineering point of view. [Spanish] Se presenta un metodo para la estimacion de la temperatura inicial en las formaciones de yacimientos geotermicos. El metodo se basa en la teoria de control donde las temperaturas medidas o registros de temperatura se comparan con las correspondientes temperaturas simuladas a diferentes tiempos con el pozo cerrado. La comparacion se hace usando un algoritmo de control el cual hace cambios a las temperaturas de yacimiento originalmente supuestas y realiza iteraciones hasta que se obtiene el mejor ajuste entre los registros de temperatura y las temperaturas simuladas. La simulacion del transporte de fluidos y calor en el pozo incluye los procesos de circulacion y paro en presencia de

  12. Evidence for Involvement of IL-9 and IL-22 in Cows' Milk Allergy in Infants.

    Science.gov (United States)

    Barros, Karina V; Flor Silveira, Vera L; Laranjeira, Marisa S; Wandalsen, Neusa F; Passeti, Susana; de Oliveira, Roberta; Munekata, Regina V; Noakes, Paul S; Miles, Elizabeth A; Calder, Philip C

    2017-09-21

    Although allergic inflammation is characterized by a T helper (Th) 2-dominant immune response, the discovery of a role for new T cell subsets in inflammatory diseases has added an additional layer of complexity to the understanding of the pathogeneses of allergic diseases. We evaluated plasma cytokine profiles in infants with cows' milk allergy (CMA), who were being treated with an elimination diet. In a prospective, randomized and controlled study, infants (aged 8.4 ± 3.9 months) with CMA were treated with an elimination diet for 120 days, which replaced cows' milk with a hydrolysed soy protein formula ( n = 26) or a free amino acid formula ( n = 20). Blood samples were collected before treatment during active disease (T0) and after 120 days, when symptoms were absent (T1). Plasma cytokine concentrations were measured. Infants with CMA had higher plasma concentrations of interleukin (IL)-4 and IL-13 and lower concentrations of IL-9, IL-17A and interferon-γ, compared with healthy breast-fed infants. At T0, there was a positive correlation between blood eosinophil numbers and plasma concentrations of IL-4, IL-9, IL-17A and IL-22. Treatment with a cows' milk elimination diet resulted in a decrease in plasma IL-4, IL-9, IL-13 and IL-22 and an increase in plasma IL-17A. We conclude that IL-4 and IL-13 are elevated in active CMA. The association of IL-9 and IL-22 with eosinophilia, and the decrease in these two cytokines with cows' milk elimination, suggests that they both play a role in the symptoms observed in CMA and may be important targets for future interventions.

  13. Potential of IL-1, IL-18 and Inflammasome Inhibition for the Treatment of Inflammatory Skin Diseases

    Directory of Open Access Journals (Sweden)

    Gabriele Fenini

    2017-05-01

    Full Text Available In 2002, intracellular protein complexes known as the inflammasomes were discovered and were shown to have a crucial role in the sensing of intracellular pathogen- and danger-associated molecular patterns (PAMPs and DAMPs. Activation of the inflammasomes results in the processing and subsequent secretion of the pro-inflammatory cytokines IL-1β and IL-18. Several autoinflammatory disorders such as cryopyrin-associated periodic syndromes and Familial Mediterranean Fever have been associated with mutations of genes encoding inflammasome components. Moreover, the importance of IL-1 has been reported for an increasing number of autoinflammatory skin diseases including but not limited to deficiency of IL-1 receptor antagonist, mevalonate kinase deficiency and PAPA syndrome. Recent findings have revealed that excessive IL-1 release induced by harmful stimuli likely contributes to the pathogenesis of common dermatological diseases such as acne vulgaris or seborrheic dermatitis. A key pathogenic feature of these diseases is IL-1β-induced neutrophil recruitment to the skin. IL-1β blockade may therefore represent a promising therapeutic approach. Several case reports and clinical trials have demonstrated the efficacy of IL-1 inhibition in the treatment of these skin disorders. Next to the recombinant IL-1 receptor antagonist (IL-1Ra Anakinra and the soluble decoy Rilonacept, the anti-IL-1α monoclonal antibody MABp1 and anti-IL-1β Canakinumab but also Gevokizumab, LY2189102 and P2D7KK, offer valid alternatives to target IL-1. Although less thoroughly investigated, an involvement of IL-18 in the development of cutaneous inflammatory disorders is also suspected. The present review describes the role of IL-1 in diseases with skin involvement and gives an overview of the relevant studies discussing the therapeutic potential of modulating the secretion and activity of IL-1 and IL-18 in such diseases.

  14. IL-25, IL-33 and TSLP receptor are not critical for development of experimental murine malaria

    Directory of Open Access Journals (Sweden)

    Akiko Shibui

    2016-03-01

    Full Text Available IL-25, IL-33 and TSLP, which are produced predominantly by epithelial cells, can induce production of Th2-type cytokines such as IL-4, IL-5 and/or IL-13 by various types of cells, suggesting their involvement in induction of Th2-type cytokine-associated immune responses. It is known that Th2-type cytokines contribute to host defense against malaria parasite infection in mice. However, the roles of IL-25, IL-33 and TSLP in malaria parasite infection remain unclear. Thus, to elucidate this, we infected wild-type, IL-25−/−, IL-33−/− and TSLP receptor (TSLPR−/− mice with Plasmodium berghei (P. berghei ANKA, a murine malaria strain. The expression levels of IL-25, IL-33 and TSLP mRNA were changed in the brain, liver, lung and spleen of wild-type mice after infection, suggesting that these cytokines are involved in host defense against P. berghei ANKA. However, the incidence of parasitemia and survival in the mutant mice were comparable to in the wild-type mice. These findings indicate that IL-25, IL-33 and TSLP are not critical for host defense against P. berghei ANKA.

  15. Psoriasis is not associated with IL-12p70/IL-12p40 production and IL12B promoter polymorphism

    DEFF Research Database (Denmark)

    Litjens, Nicolle H R; van der Plas, Mariena J A; Ravensbergen, Bep

    2004-01-01

    Psoriasis is a type-1 T cell-mediated, chronic inflammatory disease. Since interleukin (IL)-12p70 promotes the development of type-1 T cells, we investigated whether psoriasis is associated with an increased production of this cyctokine by blood cells. Results revealed that the production of IL-1...

  16. Il nuovo server per il calcolo parallelo al CILEA: HP 9000 Enterprise Server K580

    OpenAIRE

    Bonini, Francesca

    1999-01-01

    In questo articolo è presentato il nuovo server ad alte prestazioni, per il calcolo parallelo, disponibile al Cilea. In particolare, viene fornita una breve descrizione dei pacchetti software disponibili, della configurazione e delle modalità di utilizzo della macchina.

  17. Eccrine sweat contains IL-1α, IL-1β and IL-31 and activates epidermal keratinocytes as a danger signal.

    Directory of Open Access Journals (Sweden)

    Xiuju Dai

    Full Text Available Eccrine sweat is secreted onto the skin's surface and is not harmful to normal skin, but can exacerbate eczematous lesions in atopic dermatitis. Although eccrine sweat contains a number of minerals, proteins, and proteolytic enzymes, how it causes skin inflammation is not clear. We hypothesized that it stimulates keratinocytes directly, as a danger signal. Eccrine sweat was collected from the arms of healthy volunteers after exercise, and levels of proinflammatory cytokines in the sweat were quantified by ELISA. We detected the presence of IL-1α, IL-1β, and high levels of IL-31 in sweat samples. To investigate whether sweat activates keratinocytes, normal human keratinocytes were stimulated with concentrated sweat. Western blot analysis demonstrated the activation of NF-κB, ERK, and JNK signaling in sweat-stimulated keratinocytes. Real-time PCR using total RNA and ELISA analysis of supernatants showed the upregulation of IL-8 and IL-1β by sweat. Furthermore, pretreatment with IL-1R antagonist blocked sweat-stimulated cytokine production and signal activation, indicating that bioactive IL-1 is a major factor in the activation of keratinocytes by sweat. Moreover, IL-31 seems to be another sweat stimulator that activates keratinocytes to produce inflammatory cytokine, CCL2. Sweat is secreted onto the skin's surface and does not come into contact with keratinocytes in normal skin. However, in skin with a defective cutaneous barrier, such as atopic dermatitis-affected skin, sweat cytokines can directly act on epidermal keratinocytes, resulting in their activation. In conclusion, eccrine sweat contains proinflammatory cytokines, IL-1 and IL-31, and activates epidermal keratinocytes as a danger signal.

  18. Level Of Cytokines (Like IL-1 , IL-6 , IL-8 And TNF-  In Platelet Concentrates

    Directory of Open Access Journals (Sweden)

    Shayegan M

    2004-09-01

    Full Text Available Background: As increase of cytokines (like IL-1 , IL-6 , IL-8 and TNF-  in platelet concentrates (PCs during storage are involved in Febrile Non Hemolytic Transfusion Reactions (FNHTRs after Platelet transfusion, the aim of this study was the survey of these cytokines level in PCs produced in Tehran Blood Center. Materials and Methods: This study proposed to determine if WBC reduction in PCs by pre-storage leuckodepletion filters reduced the levels of these cytokines during storage uo 3 days. Each of the PCs (n = 54 was prepared from single random donor (RD by Platelet-Rich-Plasma (PRP, then were divided in four groups: 1- unfiltered non-irradiated RD-PCs (n= 13 2- unfiltered and -irradiated RD-PCs (n=16 3 - filtered non-irradiated RD-PCs (n=14 4-filtered and -irradiated RD-PCs (n = 11. Cytokines levels in PCs supernatants were measured by ELISA kits according manufacture‘s instructions. Results: Our results showed : IL-8 was increased in unfiltered non-irradiated and IL-18 in -irradiated RD-PCs but not in the filtered RD-PCs in day 3 . Compared to unfiltered PCs in filtered units, pre-storage filtration prevented a rise in the IL-8 and TNF-  in day 3 of storage .The concentration of IL-1 was lower than the minimal detectable concentration by the kits used for this purpose. IL-6 was detected only in 7 units of all filtered PCs in day 3. Conclusion: These data indicate that pre-storage leuko-reduction of PCs can prevent accumulation of IL-6, IL-8 and TNF-  during storage.

  19. 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.

  20. Endogenous suppression of mast cell development and survival by IL-4 and IL-10.

    Science.gov (United States)

    Speiran, Kelly; Bailey, Daniel P; Fernando, Josephine; Macey, Matthew; Barnstein, Brian; Kolawole, Motunrayo; Curley, Dana; Watowich, Stephanie S; Murray, Peter J; Oskeritzian, Carole; Ryan, John J

    2009-05-01

    Mast cell development is an important component of atopic and chronic inflammatory diseases such as asthma, multiple sclerosis, rheumatoid arthritis, and atherosclerosis. In this study, we found that IL-4 and IL-10 were produced constitutively in cultures of developing mast cells, correlating with mast cell purity. Deletion of either gene increased mast cell numbers and Fc epsilon RI expression during culture in IL-3 + stem cell factor (SCF). By adding exogenous IL-4 and IL-10 to bone marrow (BM) cultures containing IL-3 + SCF, we found that IL-4 + IL-10 suppressed mast cell development through mechanisms not used by either cytokine alone. IL-4 + IL-10 elicited a rapid cell death coincidental with reduced Kit receptor expression and signaling and enhanced mitochondrial damage and caspase activation. IL-4 or IL-10 costimulation, unlike either cytokine alone, altered mast cell ontogeny to yield predominantly macrophages in cultures that typically produce mast cells. This effect was observed consistently with unseparated BM cells, purified mouse BM stem cells, and erythrocyte-depleted human umbilical cord blood cells. These experiments demonstrated a major role for Stat6 and Stat3, but not the Stat3-induced transcriptional repressor Ets variant gene 3. Genetic background was also a critical factor, as BALB/c-derived BM cells were completely resistant to IL-10-mediated killing and expressed lower levels of IL-10R. Collectively, these results support the theory that IL-4 and IL-10 function as endogenous regulators of mast cell progenitor development, consistent with a role in immune homeostasis. Loss of this homeostasis, perhaps via genetic polymorphism, could contribute to the etiology of mast cell-associated disease.

  1. The Relationship of Cytokines IL-13 and IL-17 with Autoantibodies Profile in Early Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Isabela Siloşi

    2016-01-01

    Full Text Available Aims. In the present study, we aimed to assess the concentrations of IL-13 and IL-17 in serum of patients with early rheumatoid arthritis (eRA, the investigation of correlation between the concentrations of these cytokines and disease activity score, and the concentration of some autoantibodies and the evaluation of the utility of IL-13 and -17 concentration measurements as markers of disease activity. Materials and Methods. Serum samples were collected from 30 patients and from 28 controls and analysed parameters. Results. The serum concentrations of IL-13, IL-17, anti-CCP, and IgM-RF were statistically significantly higher in patients with eRA, compared to the controls. IL-13 concentrations in the severe and moderate groups with eRA were statistically higher than in the mild and control groups. Also, in the case of IL-17, serum concentrations increased proportionally with the disease activity of eRA. We observe that concentrations of IL-13 and -17 did not correlate with autoantibodies. IL-17 concentration significantly positively correlated with CRP, while IL-13 concentration significantly negatively correlated with CRP. Disease activity score, DAS28, was strongly positively correlated with levels of ESR and weakly positively correlated with concentrations of anti-RA33 autoantibodies. IL-13 has a higher diagnostic utility than IL-17, CRP, ESR, IgM-RF, and anti-CCP as markers of disease activity. Conclusions. The presence of higher IL-13 and IL-17 serum levels in patients, compared with those of controls, confirms that these markers, found with high specificity, might be involved in the pathogenesis of eRA. IL-13 and IL-17 might be of better usefulness in the prediction of eRA activity status than IgM-RF and anti-CCP.

  2. IL-2 loaded dextran microspheres with attractive histocompatibility properties for local IL-2 cancer therapy

    NARCIS (Netherlands)

    Koten, JW; Van Luyn, MJA; Cade, JA; Hennink, WE; Bijleveld, C; Den Otter, W

    2003-01-01

    Biodegradable dextran microspheres (MS) were developed as a slow-release system for interleukin-2 (IL-2) to apply them for local IL-2 therapy of cancer. We describe the tissue reactions induced by these MS without or with IL-2 in rats. Dextran MS stain bright red-purple with the periodic acid Schiff

  3. [Correlation of serum IL-16, IL-18 levels and immunoglobulins in children with asthma].

    Science.gov (United States)

    Xue, Yi-Nan; Zou, Xian-De; Wu, Jia-Ling

    2006-02-01

    This study examined the changes of serum levels of interleukin (IL)-16, IL-18 and immunoglobulins and the correlation of serum IL-16, IL-18 levels and immunoglobulins in children with asthma and aimed to explore the role of IL-16, IL-18 and immunoglobulins in the pathogenesis of asthma. Thirty-four children with asthma and 21 age and gender-matched healthy children were enrolled in this study. The levels of IL-16, IL-18 and immunoglobulin E (IgE) were determined using ELISA. Immunoglobulin G (IgG), immunoglobulin M (IgM) and immunoglobulin A (IgA) were detected by immunoturbidimetry. The levels of IL-16, IL-18 and IgE in patients with asthma at both acute attack and convalescence stages were significantly higher than those in healthy controls. An increased IgG and a decreased IgA levels were found in asthmatic patients at the acute attack stage. There was a positive correlation between the IL-16 and IL-18 levels at both acute attack and convalescence stages of asthma (r=0.70, P attack stage of asthma (r=0.624, P asthma. The immunologic imbalance exists in children with asthma at both acute attack and convalescence stages. Anti-allergic therapy should be administered through the acute attack to the convalescence stages of asthma.

  4. Serum IL17 and IL4R RS1805010 genotypes: relationship with ...

    African Journals Online (AJOL)

    Egyptian Journal of Biochemistry and Molecular Biology ... The current study aimed to assess serum IL17 level in Egyptian patients with RA according toIL4Rrs1805010 genotypes,and to detect possibleassociations ... Meanwhile, serum IL17 levels and Larsen score had significant positive correlation only in GG patients.

  5. La ricerca di un modello di insegnamento. Il laboratorio della progettazione architettonica / The search for a teaching model. The workshop of architectural design

    Directory of Open Access Journals (Sweden)

    Antonio Tejedor Cabrera

    2014-03-01

    Full Text Available L’autore riflette sull’insegnamento del Progetto Architettonico come materia principale nelle Scuole di Architettura e l’importanza del laboratorio come modello di insegnamento. Questo si è diventato pratica abituale per una formazione maggiormente qualificata, associata a corsi estivi e a programmi complementari di apprendimento, per la preparazione dei futuri architetti. Tuttavia, nell’organizzazione dei corsi di Progettazione, il laboratorio si configura prevalentemente come spazio di lavoro, in cui l’alunno accresce le sue conoscenze, scopre la maniera per risolvere i problemi, trae conclusioni, esercita le sue abilità, trova un suo particolare metodo di progettare e, in conclusione, identifica l’esperienza con la libertà creativa. / The author reflects on the teaching of Architectural Design as a core subject in the Schools of Architecture and the relevance of the workshop as a teaching model. It has become common practice for more specialized training associated with summer courses and complementary learning programs for the training of future architects. However, in the organization of the teaching of Architectural Design, the workshop prevails as the workspace where the student increases their knowledge, learns how to solve problems, draws conclusions, exercises their skills, finds his or her particular method of designing and, finally, identifies the experience with creative freedom.

  6. Knocking out IL-6 by vaccination

    DEFF Research Database (Denmark)

    Galle, Pia; Hougs, Lotte; Barington, Torben

    2004-01-01

    Inappropriate expression of IL-6 plays a role in various inflammatory conditions, degenerative diseases, and cancers. Several model systems have been developed that can specifically block IL-6-receptor interactions. Here we present a simple and highly effective approach based on vaccination...

  7. Effects of HV-CRRT on PCT, TNF-α, IL-4, IL-6, IL-8 and IL-10 in patients with pancreatitis complicated by acute renal failure.

    Science.gov (United States)

    Liu, Changbo; Li, Mu; Cao, Shixiong; Wang, Jianzhong; Huang, Xiaoqiong; Zhong, Weizhen

    2017-10-01

    The aim of the study was to investigate the effects of high-volume continuous renal replacement therapy (HV-CRRT) on procalcitonin (PCT), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-8 and IL-10 in acute pancreatitis complicated by acute renal failure. Eighty-six patients with acute pancreatitis complicated with acute renal failure were selected from September 2014 to September 2016 in our hospital, and were treated by continuous veno-venous hemofiltration (CVVH). The patients were randomly divided into the observation group, treated by the HV-CVVH model with a displacement rate of 4 l/h, and the control group, treated by the normal capacity model with a displacement rate of 2 l/h. The levels of PCT, TNF-α, IL-4, IL-6, IL-8, and IL-10 in serum were measured by ELISA before and 2, 6 and 12 h after treatment, and 12 h after CVVH. The serum PCT and TNF-α levels in the two groups were decreased at 2 h after treatment. The lowest levels appeared at 6 h after treatment, and then recovered, but remained lower than those before treatment (ptreatment, and the decreases in the observation group were more obvious than those in the control group (ptreatment of pancreatitis complicated by acute renal failure. Additionally, replacement of the blood filter at appropriate time-points can improve the treatment efficacy.

  8. Monoclonal Antibodies Against IL-13 and IL-31RA in Development for Atopic Dermatitis

    DEFF Research Database (Denmark)

    Hamann, Carsten R; Thyssen, Jacob P

    2017-01-01

    phase two trial has been completed for a humanized antibody against IL-31 receptor alpha, one subunit of the IL-31 receptor complex. This study showed significant dose-dependent reductions in pruritus, EASI scores, and markers of sleep quality. Initial clinical trials for monoclonal antibodies against......The IL-13 and IL-31 cytokines and inflammatory pathways have been identified as important for atopic dermatitis (AD) pathophysiology. Monoclonal antibodies against IL-13 have been studied for the treatment of asthma since 2011. More recently, two phase two trials have been completed...

  9. Method to estimate the convective mixing height from atmospheric sounding data; Un metodo para estimar la altura de la capa de mezcla a partir de datos de radiosondeo atmosferico

    Energy Technology Data Exchange (ETDEWEB)

    Salcido, Alejandro [Instituto de Investigaciones Electricas, Temixco, Morelos (Mexico); Castro, Telma [Universidad Nacional Autonoma de Mexico, Mexico, D.F. (Mexico)

    2000-07-01

    A simple method to estimate the convective mixing height from atmospheric sounding data is presented in this paper. The proposed method is based on the slab model of the atmospheric boundary layer, which assumes that virtual potential temperature remains constant in the mixed layer, increases linearly with height in the free atmosphere, and has a discontinuity at the entrainment layer (in fact, the entrainment layer is assumed to be infinitesimal in depth). The proposed method was applied in Mexico City in order to estimate the mixing height values for 5:00 and 17:00 hours (local time) from January to May of 1993 and 1994. [Spanish] En este trabajo se presenta un metodo para estimar la altura de la capa de mezcla a partir de los datos de radiosondeo atmosferico. El metodo esta basado en un modelo de la capa limite atmosferica donde la temperatura potencial virtual se mantiene constante en la capa de mezclado, sufre una discontinuidad en la zona de entrainment (el espesor de la cual se supone infinitesimal), y crece linealmente con la altura en la atmosfera libre. El metodo desarrollado se utilizo para la determinacion de la altura de la capa de mezcla de la Ciudad de Mexico para las 11:00z y 23:00z de los dias de los meses de enero a mayo de los anos de 1993 y 1994.

  10. IL-17-producing NKT cells depend exclusively on IL-7 for homeostasis and survival.

    Science.gov (United States)

    Webster, K E; Kim, H-O; Kyparissoudis, K; Corpuz, T M; Pinget, G V; Uldrich, A P; Brink, R; Belz, G T; Cho, J-H; Godfrey, D I; Sprent, J

    2014-09-01

    Natural killer T (NKT) cells are innate-like T cells that rapidly recognize pathogens and produce cytokines that shape the ensuing immune response. IL-17-producing NKT cells are enriched in barrier tissues, such as the lung, skin, and peripheral lymph nodes, and the factors that maintain this population in the periphery have not been elucidated. Here we show that NKT17 cells deviate from other NKT cells in their survival requirements. In contrast to conventional NKT cells that are maintained by IL-15, RORγt(+) NKT cells are IL-15 independent and instead rely completely on IL-7. IL-7 initiates a T-cell receptor-independent (TCR-independent) expansion of NKT17 cells, thus supporting their homeostasis. Without IL-7, survival is dramatically impaired, yet residual cells remain lineage committed with no downregulation of RORγt evident. Their preferential response to IL-7 does not reflect enhanced signaling through STAT proteins, but instead is modulated via the PI3K/AKT/mTOR signaling pathway. The ability to compete for IL-7 is dependent on high-density IL-7 receptor expression, which would promote uptake of low levels of IL-7 produced in the non-lymphoid sites of lung and skin. This dependence on IL-7 is also reported for RORγt(+) innate lymphoid cells and CD4(+) Th17 cells, and suggests common survival requirements for functionally similar cells.

  11. IL-4 function can be transferred to the IL-2 receptor by tyrosine containing sequences found in the IL-4 receptor alpha chain.

    Science.gov (United States)

    Wang, H Y; Paul, W E; Keegan, A D

    1996-02-01

    IL-4 binds to a cell surface receptor complex that consists of the IL-4 binding protein (IL-4R alpha) and the gamma chain of the IL-2 receptor complex (gamma c). The receptors for IL-4 and IL-2 have several features in common; both use the gamma c as a receptor component, and both activate the Janus kinases JAK-1 and JAK-3. In spite of these similarities, IL-4 evokes specific responses, including the tyrosine phosphorylation of 4PS/IRS-2 and the induction of CD23. To determine whether sequences within the cytoplasmic domain of the IL-4R alpha specify these IL-4-specific responses, we transplanted the insulin IL-4 receptor motif (I4R motif) of the huIL-4R alpha to the cytoplasmic domain of a truncated IL-2R beta. In addition, we transplanted a region that contains peptide sequences shown to block Stat6 binding to DNA. We analyzed the ability of cells expressing these IL-2R-IL-4R chimeric constructs to respond to IL-2. We found that IL-4 function could be transplanted to the IL-2 receptor by these regions and that proliferative and differentiative functions can be induced by different receptor sequences.

  12. Diagnostic value of combined determination of serum and chest fluid adenosine deaminase (ADA), IL-2, IL-6, IL-10 contents for differentiation of tuberculous from malignant pleural effusion

    International Nuclear Information System (INIS)

    Wu Jiaming; Wang Limin

    2005-01-01

    Objective: To investigate the possible diagnostic value of combined determination of serum and chest fluid contents of ADA, IL-2, IL-6, IL-10 in patients with tuberculous and malignant pleural effusion. Methods: Serum and chest fluid ADA (with biochemical method), IL-2, IL-6, IL-10 (with ELISA) contents were measured in 56 patients with tuberculosis pleural effusion, 53 patients with malignant effusion and 30 controls (in serum only). The receiving operative characteristic (ROC) curve for each parameter was analyzed for study of respective area under curse (Auc). Results: The serum IL-6 levels in both groups of patients were significantly higher than those in the controls (P<0.05). The chest fluid contents of ADA, IL-2, IL-6 and IL-10 in patients with tuberculous effusion were all significantly higher than those in patients with malignancies (P<0.05). The Auc in the ROC was largest in the case of ADA, followed by IL-10, IL-6 with IL-2 the least. Conclusion: Determination of chest fluid ADA, IL-2, IL-6, IL-10 contents was helpful in the differentiation of tuberculous from malignant pleural effusion. Combined determination of chest fluid ADA and IL-10 provided the highest accuracy rate for differentional diagnosis. (authors)

  13. Expression of IL-18, IL-18 Binding Protein, and IL-18 Receptor by Normal and Cancerous Human Ovarian Tissues: Possible Implication of IL-18 in the Pathogenesis of Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Liat Medina

    2014-01-01

    Full Text Available Proinflammatory cytokine IL-18 has been shown to be elevated in the sera of ovarian carcinoma patients. The aim of the study was to examine the levels and cellular origin of IL-18, IL-18 binding protein, and IL-18 receptor in normal and cancerous ovarian tissues. Ovarian tissue samples were examined by immunohistochemical staining for IL-18, IL-18BP, and IL-18R and mRNA of these cytokines was analyzed with semiquantitative PT-PCR. IL-18 levels were significantly higher in cancerous ovarian tissues (P=0.0007, IL-18BP levels were significantly higher in normal ovarian tissues (P=0.04, and the ratio of IL-18/IL-18BP was significantly higher in cancerous ovarian tissues (P=0.036. Cancerous ovarian tissues expressed significantly higher IL-18 mRNA levels (P=0.025, while there was no difference in the expression of IL-18BP mRNA and IL-18R mRNA between cancerous and normal ovarian tissues. IL-18 and IL-18BP were expressed dominantly in the epithelial cells of both cancerous and normal ovarian tissues, while IL-18R was expressed dominantly in the epithelial cells of cancerous ovarian tissues but expressed similarly in the epithelial and stromal cells of normal cancerous tissues. This study indicates a possible role of IL-18, IL-18BP, and IL-18R in the pathogenesis of epithelial ovarian carcinoma.

  14. Protection from RNA and DNA viruses by IL-32.

    NARCIS (Netherlands)

    Zepp, J.A.; Nold-Petry, C.A.; Dinarello, C.A.; Nold, M.F.

    2011-01-01

    Several studies have documented a proinflammatory role for IL-32, which induces IL-1alpha, IL-1beta, IL-6, TNF, and chemokines via NF-kappaB, p38MAPK, and AP-1. However, IL-32 also participates in the responses to infection with viruses such as HIV-1 and influenza. In this study, we explored these

  15. Allergic Rhinitis and Its Relationship with IL-10, IL-17, TGF-β, IFN-γ, IL 22, and IL-35

    Directory of Open Access Journals (Sweden)

    P. Bayrak Degirmenci

    2018-01-01

    Full Text Available Background. We aimed in our study to research the role of new cytokines such as IL-35, IL-22, and IL-17 that may form a target for novel treatment approaches. Methods. IL-10, IL-17, TGF-β, IFN-γ, IL-22, and IL-35 serum levels of allergic rhinitis (AR patients were measured using ELISA method. Allergic sensitization was demonstrated by the skin prick test. Patients only with olive tree sensitivity were evaluated for seasonal AR (SAR. Patients only with mite sensitivity were included in the study for perennial AR (PAR. AR clinic severity was demonstrated by the nasal symptom scores (NSS. Results. In total, 65 AR patients (patient group, having 31 PAR and 34 SAR patients, and 31 healthy individuals (control group participated in the study. Cytokine levels between the patient group and the control group were compared; IL-17 (p=0.038, IL-22 (p=0.001, and TGF-β (p=0.031 were detected as high in the patient group, and IFN-γ (p<0.001 was detected as low in the patient group. When correlation analysis was made between age, gender, prick test result, NSS, AR duration, and cytokine levels in the patient group, a negative correlation was detected only between IFN-γ (p=0.032/r=−0.266 level and NSS. Conclusions. Accompanied by the literature information, these results made us think that T cell subgroups and cytokines have an important role in AR immunopathogenesis. It is thought that future studies to be conducted relating to this subject will form new targets in treatment.

  16. Google e il patrimonio culturale italiano

    Directory of Open Access Journals (Sweden)

    Elisa Bonacini

    2014-04-01

    Full Text Available ITIn questo lavoro si intende ricostruire il ruolo svolto dal motore di ricerca google nella moderna società culturale e, soprattutto, il ruolo svolto da google nella comunicazione e valorizzazione del patrimonio culturale italiano attraverso il cultural institute e tutti i software e gli applicativi che google mette a disposizione della cultura.ENAim of this paper is the reconstruction of google’s role in modern cultural society and, above all, its role through the google cultural institute and its many softwares and applications, for communication and dissemination of italian cultural heritage.

  17. IL-2/anti-IL-2 mAb immunocomplexes: A renascence of IL-2 in cancer immunotherapy?

    Czech Academy of Sciences Publication Activity Database

    Tomala, Jakub; Kovář, Marek

    2016-01-01

    Roč. 5, č. 3 (2016), e1102829 ISSN 2162-402X R&D Projects: GA ČR GA13-12885S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61388971 Keywords : Anti-IL-2 mAb * cancer immunotherapy * IL-2 Subject RIV: EE - Microbiology, Virology Impact factor: 7.719, year: 2016

  18. Il turismo è un fenomeno spaziale

    Directory of Open Access Journals (Sweden)

    Pasquale Boccagna

    2010-10-01

    Full Text Available Il turismo e le attività da esso generate si combinano con il fattore territoriale dando luogo al processo di fruizione del servizio turistico caratterizzato essenzialmente dalla contestualità dell’erogazione e del consumo di un’entità in buona parte immateriale in un contesto geografico scelto dal consumatore e definito destinazione turistica. Se la chiarificazione del concetto di turismo e di prodotto turistico è risultata essenziale per spiegare in un certo senso le ragioni dell’offerta (perché nascono e si sviluppano le attività turistiche?, altrettanto significativa sembra l’opportunità di enucleare, tra le varie definizioni che sono state proposte nella letteratura specialistica, gli elementi caratteristici della destinazione turistica per arrivare alla spiegazione delle ragioni del management del sistema di offerta (prodotto complesso e globale. Le domande di fondo sono: Cosa spinge i turisti a partire dal luogo di abituale dimora per recarsi in una località che presenta caratteristiche naturali, ambientali e culturali completamente diverse dalla regione di partenza? Cosa fa trasformare un territorio in una destinazione? Perché alcuni flussi turistici prediligono determinate destinazioni rispetto alle altre? Quale è l’impatto sul piano della mobilità territoriale ed urbana? Il sistema dei trasporti può essere considerato una risorsa generatrice di vantaggi competitivi per una destinazione turistica? Il framework dell’articolo è rappresentato dalla teoria marshalliana del distretto industriale che pone il territorio e le sue risorse alla base dello sviluppo del sistema locale. Ad esso si tenta di sovrapporre il framework VRIO (Valore, Rarità, Inimitabilità, Organizzazione, derivato dalla Resource Based View, per stabilire se una determinata risorsa del territorio, nel caso di specie il sistemi di trasporto urbano ed extraurbano, può generare un vantaggio competitivo sostenibile e duraturo. Per l’analisi delle

  19. The role of interleukin-5 (IL-5 in vivo: studies with IL-5 deficient mice

    Directory of Open Access Journals (Sweden)

    Klaus I Matthaei

    1997-12-01

    Full Text Available Eosinophil recruitment is a characteristic feature of a number of pathological conditions and was the topic of the recent International Symposium on allergic inflammation, asthma, parasitic and infectious diseases (Rio de Janeiro, June 3-5, 1996. Since interleukin5 (IL5 is believed to regulate the growth, differentiation and activation of eosinophils (Coffman et al. 1989, Sanderson 1992, the role of eosinophils and IL5 are closely linked. Although IL5 specifically regulates eosinophilia in vivo and this is its most well established activity, it is becoming clear that IL5 also has other biological effects. The recent derivation of an IL5 deficient mouse (Kopf et al. 1996, provides a model for exploring not only the role of IL5 and eosinophils but also other novel activities of IL5. Of note is that although the IL5 deficient mice cannot elicit a pronounced eosinophilia in response to inflammatory stimulation following aeroallergen challenge or parasite infection they still produce basal levels of eosinophils that appear to be morphologically and functionally normal. However, the basal levels of eosinophils appear insufficient for normal host defence as IL5 deficiency has now been shown to compromise defence against several helminth infections. In addition, IL5 deficient mice appear to have functional deficiencies in B-1 B lymphocytes and in IgA production.

  20. Cytokine vaccination: neutralising IL-1alpha autoantibodies induced by immunisation with homologous IL-1alpha

    DEFF Research Database (Denmark)

    Svenson, M; Hansen, M B; Thomsen, Allan Randrup

    2000-01-01

    High-affinity IgG autoantibodies (aAb) to IL-1alpha are among the most frequently found aAb to cytokines in humans. To establish an animal model with aAb to IL-1alpha, we immunised mice with recombinant murine IL-1alpha. Unprimed and Bacille Calmette-Guérin (BCG)-primed BALB/cA mice were vaccinated...... in mice by vaccination with recombinant murine IL-1alpha conjugated to PPD. Studies of the effects of IL-1alpha aAb in such animals may help clarify the importance of naturally occurring IL-1alpha aAb in humans and permit the evaluation of future therapies with cytokine aAb in patients...... with IL-1alpha coupled to purified protein derivative of tuberculin (PPD). Both unprimed and primed animals developed IgG aAb to IL-1alpha. These aAb persisted at high levels more than 100 days after vaccination and did not cross-react with murine IL-1beta. The induced anti-IL-1alpha aAb inhibited binding...

  1. Abitare e conservare il patrimonio architettonico. Il caso del Convento di Cristo, 1979-2009.

    Directory of Open Access Journals (Sweden)

    Alvaro Barbosa

    2010-12-01

    Full Text Available Abitare è rimanere in un luogo. È interagire con lo spazio, il paesaggio, la natura e gli uomini. Il risultato di quest’azione permane come un segno nel territorio ed è trasmessa alle generazioni future col passare del tempo. In questo modo a si afferma il concetto di patrimonio associato all’azione dell’abitare un luogo sia questo una casa, sia un convento, una città, un paesaggio costruito, etc. I luoghi del patrimonio sono il supporto fisico della memoria sociale, la quale è trasmessa nell’atto stesso del vivere umano. Così la memoria degli uomini è radicata nel modo in cui loro abitano i luoghi. Togliere ai luoghi questa caratteristica di vita, questa funzione dell’abitare, riduce drasticamente il senso del patrimonio ed il suo ruolo di monumento, di memoria vivente. Cercare di mantenere vivo il patrimonio, nelle sue diverse valenze, è il compito principale della società odierna rispetto al patrimonio costruito. Si può affermare che oggi conosciamo tutte le soluzioni tecniche per la conservazione dei monumenti. Non disponiamo tuttavia delle soluzioni sociali capaci di mantenerli viventi e attuanti nel nostro mondo contemporaneo. Il caso del Convento di Cristo diventa un paradigma di questa lotta per una nuova strategia di conservazione centrata sul vivere i luoghi, sull’abitare il patrimonio.

  2. B cells produce less IL-10, IL-6 and TNF-α in myasthenia gravis.

    Science.gov (United States)

    Yilmaz, Vuslat; Oflazer, Piraye; Aysal, Fikret; Parman, Yeşim G; Direskeneli, Haner; Deymeer, Feza; Saruhan-Direskeneli, Güher

    2015-06-01

    B cells from myasthenia gravis (MG) patients with autoantibodies (Aab) against acetylcholine receptor (AChR), muscle-specific kinase (MuSK) or with no detectable Aab were investigated as cytokine producing cells in this study. B cells were evaluated for memory phenotypes and expressions of IL-10, IL-6 and IL-12A. Induced productions of IL-10, IL-6, IL-12p40, TNF-α and LT from isolated B cells in vitro were measured by immunoassays. MG patients receiving immunosuppressive treatment had higher proportions of memory B cells compared with healthy controls and untreated patients. With CD40 stimulation MG patients produced significantly lower levels of IL-10, IL-6. With CD40 and B cell receptor stimulation of B cells, TNF-α production also decreased in addition to these cytokines. The lower levels of these cytokine productions were not related to treatment. Our results confirm a disturbance of B cell subpopulations in MG subgroups on immunosuppressive treatment. B cell derived IL-10, IL-6 and TNF-α are down-regulated in MG, irrespective of different antibody productions. Ineffective cytokine production by B cells may be a susceptibility factor in dysregulation of autoimmune Aab production.

  3. Statistical elements in calculations procedures for air quality control; Elementi di statistica nelle procedure di calcolo per il controllo della qualita' dell'aria

    Energy Technology Data Exchange (ETDEWEB)

    Mura, M.C. [Istituto Superiore di Sanita' , Laboratorio di Igiene Ambientale, Rome (Italy)

    2001-07-01

    The statistical processing of data resulting from the monitoring of chemical atmospheric pollution aimed at air quality control is presented. The form of procedural models may offer a practical instrument to the operators in the sector. The procedural models are modular and can be easily integrated with other models. They include elementary calculation procedures and mathematical methods for statistical analysis. The calculation elements have been developed by probabilistic induction so as to relate them to the statistical analysis. The calculation elements have been developed by probabilistic induction so as to relate them to the statistical models, which are the basis of the methods used for the study and the forecast of atmospheric pollution. This report is part of the updating and training activity that the Istituto Superiore di Sanita' has been carrying on for over twenty years, addressed to operators of the environmental field. [Italian] Il processo di elaborazione statistica dei dati provenienti dal monitoraggio dell'inquinamento chimico dell'atmosfera, finalizzato al controllo della qualita' dell'aria, e' presentato in modelli di procedure al fine di fornire un sintetico strumento di lavoro agli operatori del settore. I modelli di procedure sono modulari ed integrabili. Includono gli elementi di calcolo elementare ed i metodi statistici d'analisi. Gli elementi di calcolo sono sviluppati con metodo d'induzione probabilistica per collegarli ai modelli statistici, che sono alla base dei metodi d'analisi nello studio del fenomeno dell'inquinamento atmosferico anche a fini previsionali. Il rapporto si inserisce nell'attivita' di aggiornamento e di formazione che fin dagli anni ottanta l'Istituto Superiore di Sanita' indirizza agli operatori del settore ambientale.

  4. Tecnologia italiana per il vuoto spinto

    CERN Multimedia

    2002-01-01

    "Ancora una volta ad aggiudicarsi un ambito riconoscimento internazionale e' un fisico italiano: Cristoforo Benvenuti ritirera' tra pochi giorni a Denver il premio Gaede-Langmuir che viene assegnato dalla American vacuum society" (1/2 page).

  5. Michel Foucault e il problema della genealogia

    Directory of Open Access Journals (Sweden)

    Enrico Abeni

    2011-01-01

    Full Text Available "Si j'étais prétentieux, je donnerais comme titre général à ce que je fais : généalogie de la morale." Dietro questa affermazione, rilasciata nel contesto colloquiale di un'intervista, è possibile scorgere il segno di una confessione intellettuale e il compendio di un pensiero. In primo luogo, allusivamente, rinvia alla figura di Nietzsche e alla traccia indelebile che il suo pensiero ha lasciato nella filosofia e nella ricerca di Foucault. In secondo luogo, autorizza a osservare nella riflessione foucaultiana la filigrana di quella genealogia che il presente lavoro si propone di affrontare come stile d'interrogazione filosofica.

  6. PER ALDO NOSEDA: IL CRITICO MUSICALE

    Directory of Open Access Journals (Sweden)

    Chiara Fiaccadori

    2014-03-01

    Full Text Available Il presente articolo è un tentativo di fornire la lista completa degli scritti di Aldo Noseda (Milano, 1853-Stresa, 1916 come critico musicale. Fu un erudito conoscitore d’arte e appassionato collezionista, ma la quasi totalità dei suoi scritti sono dedicati alla scena musicale italiana. Prese parte all’infiammato dibattito a proposito della musica strumentale divenendo membro della Società del Quartetto e fondando la Società orchestrale della Scala a Milano. Dal 1876 al 1894, sotto lo pseudonimo de Il Misovulgo fu tra gli editorialisti militanti di importanti periodici come «La Gazzetta musicale di Milano», il «Corriere della Sera» e «Il Caffè», contribuendovi con una serie di appassionate recensioni dei contemporanei eventi musicali milanesi.

  7. Il viaggio gastronomico di Paolo Monelli

    Directory of Open Access Journals (Sweden)

    Alberto Salarelli

    2013-01-01

    Full Text Available Il ghiottone errante di Paolo Monelli, pubblicato nel 1935, rappresenta uno dei primi esempi di narrativa di viaggio in tema di enogastronomia, un genere destinato a grande successo nel secondo dopoguerra. In questo articolo, oltre a ripercorrere la vicenda biografica di Monelli, si sottolineano le relazioni tra Il ghiottone e la cultura gastronomica del regime fascista, e si evidenziano alcuni tratti caratteristici del suo stile di scrittura.

  8. Increasing the biological activity of IL-2 and IL-15 through complexing with anti-IL-2 mAbs and Il-15Ralfa-Fc chimera

    Czech Academy of Sciences Publication Activity Database

    Votavová, Petra; Tomala, Jakub; Kovář, Marek

    2014-01-01

    Roč. 195, č. 1 (2014), s. 1-10 ISSN 0165-2478 R&D Projects: GA ČR GAP301/11/0325; GA MŠk(CZ) ED1.1.00/02.0109; GA ČR GA13-12885S Institutional support: RVO:61388971 Keywords : IL-2 * IL-15 * chimera Subject RIV: EC - Immunology Impact factor: 2.512, year: 2014

  9. IL-9-Producing Mast Cell Precursors and Food Allergy

    Science.gov (United States)

    2016-10-01

    signaling enhances or attenuates allergic responses to food allergens. Methods: Mice of an IL-25 transgenic mouse line (iIL-25Tg mice), which...developing experimental food allergy, we generated IL-25 transgenic mouse lines (iIL-25Tg mice) that constitutively overexpress murine IL-25 driven by the...AD______________ AWARD NUMBER: W81XWH-15-1-0517 TITLE: IL-9-Producing Mast Cell Precursors and Food Allergy PRINCIPAL INVESTIGATOR: Dr. Yui

  10. Il processo Andreotti. Il confine labile fra la partecipazione e il concorso esterno nei reati associativi

    Directory of Open Access Journals (Sweden)

    Paolo Intoccia

    2017-11-01

    Full Text Available Prendendo in esame un procedimento penale d’eccezione nel presente elaborato ci si propone di condurre uno studio sul diritto penale ‘in azione’ allo scopo di verificare i meccanismi di applicazione dei reati di associazione per delinquere ‘semplice’ (a. 416 c.p. e di tipo mafioso (a. 416 bis c.p.. La seguente analisi ricostruisce, infatti, l’intensa trafila giudiziaria che ha visto protagonista Giulio Andreotti – dal 4 marzo 1993 chiamato a rispondere, prima a titolo di concorrente esterno e successivamente in qualità di partecipe, dei due reati associativi sopra richiamati a fronte di un apparato accusatorio qualitativamente complesso e temporalmente imponente. Sarà in tal modo possibile verificare quanto possa essere labile, specie ove si discuta della condotta di fiancheggiamento di un soggetto politico ad un sodalizio di tipo mafioso (qui Cosa Nostra, il confine tra la fenomenologia partecipativa (nel ruolo di intraneus all’associazione e quella concorsuale eventuale (nel ruolo di cd. concorrente esterno nei delitti associativi di cui agli artt. 416 e 416 bis c.p. Parole chiave: Andreotti, Cosa Nostra, zona grigia, reati associativi, mala informazione   By examining an exceptional criminal proceeding in this paper we propose to conduct a study on criminal law ‘in action’ in order to verify the mechanisms of application of two associative offenses (‘simple’ criminal conspiracy and mafia-type criminal conspiracy. As a matter of fact the analysis reconstructs the intense trial about Giulio Andreotti’s working with Cosa Nostra – Andreotti, starting from March 4 1993, is accused of being at first an external competitor and subsequently a participant of Cosa Nostra in connection with a qualitatively complex accusatory apparatus. As a result of this analysis we come to ascertain how fleeting the boundary between the role of partecipant and external competitor in a criminal conspiracy can be, especially in case of

  11. IL-6 and IL-8 level change in patients with PVR

    International Nuclear Information System (INIS)

    Han Li'na; Pan Xin; Zhang Xiaoguang

    2002-01-01

    Objective: To investigate the changes of interleutin-6 and interleutin-8 contents in vitreous body, sub-retinal fluid and serum of patients with proliferating vitro retinopathy. Methods: The levels of IL-6 and IL-8 in vitreous body, sub-retinal fluid and serum in thirty-four patients with PVR were measured with RIA. Another thirty patients with retina detachment were used as control group. Results: The level of IL-6 and IL-8 in vitreous body and sub-retinal fluid in the experiment group were significantly higher than those in control group, but the serum levels of IL-6 and IL-8 were about the same in both groups. Conclusion: The immunological system took part in the process of PVR mainly through local mechanism

  12. Cytokine vaccination: neutralising IL-1alpha autoantibodies induced by immunisation with homologous IL-1alpha

    DEFF Research Database (Denmark)

    Svenson, M; Hansen, M B; Thomsen, Allan Randrup

    2000-01-01

    High-affinity IgG autoantibodies (aAb) to IL-1alpha are among the most frequently found aAb to cytokines in humans. To establish an animal model with aAb to IL-1alpha, we immunised mice with recombinant murine IL-1alpha. Unprimed and Bacille Calmette-Guérin (BCG)-primed BALB/cA mice were vaccinat...

  13. Differential Regulation of IL-1β and IL-6 Release in Murine Macrophages.

    Science.gov (United States)

    Hirano, Seishiro; Zhou, Quan; Furuyama, Akiko; Kanno, Sanae

    2017-12-01

    Asbestos and silica (exogenous danger) and adenosine triphosphate (ATP, endogenous danger-signaling molecule) synergistically increase IL-1β release from endotoxin-primed macrophage, which is mediated by NOD-like receptor protein 3 (NLRP3) inflammasome. However, the conversion of pro-IL-1β to its active form seems to depend on the macrophage cell types. In the present study, bone marrow-derived macrophages (BMM) and three murine macrophage cell lines, J774.1, J774A.1, and RAW264.7 were exposed to ATP or fibrous titanium dioxide (FTiO 2 ) in the presence or absence of lipopolysaccharide (LPS), and the concentrations of IL-1β and IL-6 in both cell lysates and in the culture media were measured by immunoblotting to differentiate active form of IL-1β from pro-IL-1β. IL-1β release was synergistically increased when the cells were exposed to both LPS and ATP or FTiO 2 , while IL-6 was readily released by LPS alone. IL-1β released into the culture medium was pro-IL-1β in J774.1 and RAW264.7, and most of the pro-IL-1β remained inside the cells. In contrast, the active form of IL-1β was released together with pro-IL-1β from J774A.1 and BMM after the co-stimulation. J774A.1 and BMM express apoptosis-associated speck-like protein contains a carboxyl-terminal CARD (ASC) while J774.1 and RAW264.7 do not or only faintly express ASC, and accordingly, caspase-1, which converts pro-IL-1β to its active form, is activated only in J774A.1 and BMM. Collectively, the canonical inflammasome pathway is not activated in J774.1 and RAW264.7, and the apparent synergistical increase of IL-1β in the culture medium mostly reflects the leakage of pro-IL-1β from these cells.

  14. Extracellular IL-33 cytokine, but not endogenous nuclear IL-33, regulates protein expression in endothelial cells.

    Science.gov (United States)

    Gautier, Violette; Cayrol, Corinne; Farache, Dorian; Roga, Stéphane; Monsarrat, Bernard; Burlet-Schiltz, Odile; Gonzalez de Peredo, Anne; Girard, Jean-Philippe

    2016-10-03

    IL-33 is a nuclear cytokine from the IL-1 family that plays important roles in health and disease. Extracellular IL-33 activates a growing number of target cells, including group 2 innate lymphoid cells, mast cells and regulatory T cells, but it remains unclear whether intracellular nuclear IL-33 has additional functions in the nucleus. Here, we used a global proteomic approach based on high-resolution mass spectrometry to compare the extracellular and intracellular roles of IL-33 in primary human endothelial cells, a major source of IL-33 protein in human tissues. We found that exogenous extracellular IL-33 cytokine induced expression of a distinct set of proteins associated with inflammatory responses in endothelial cells. In contrast, knockdown of endogenous nuclear IL-33 expression using two independent RNA silencing strategies had no reproducible effect on the endothelial cell proteome. These results suggest that IL-33 acts as a cytokine but not as a nuclear factor regulating gene expression in endothelial cells.

  15. Aspirin induces IL-4 production: augmented IL-4 production in aspirin-exacerbated respiratory disease

    Science.gov (United States)

    Kong, Su-Kang; Soo Kim, Byung; Gi Uhm, Tae; Soo Chang, Hun; Sook Park, Jong; Woo Park, Sung; Park, Choon-Sik; Chung, Il Yup

    2016-01-01

    Aspirin hypersensitivity is a hallmark of aspirin-exacerbated respiratory disease (AERD), a clinical syndrome characterized by the severe inflammation of the respiratory tract after ingestion of cyclooxygenase-1 inhibitors. We investigated the capacity of aspirin to induce interleukin-4 (IL-4) production in inflammatory cells relevant to AERD pathogenesis and examined the associated biochemical and molecular pathways. We also compared IL-4 production in peripheral blood mononuclear cells (PBMCs) from patients with AERD vs aspirin-tolerant asthma (ATA) upon exposure to aspirin. Aspirin induced IL-4 expression and activated the IL-4 promoter in a report assay. The capacity of aspirin to induce IL-4 expression correlated with its activity to activate mitogen-activated protein kinases, to form DNA–protein complexes on P elements in the IL-4 promoter and to synthesize nuclear factor of activated T cells, critical transcription factors for IL-4 transcription. Of clinical importance, aspirin upregulated IL-4 production twice as much in PBMCs from patients with AERD compared with PBMCs from patients with ATA. Our results suggest that IL-4 is an inflammatory component mediating intolerance reactions to aspirin, and thus is crucial for AERD pathogenesis. PMID:27534531

  16. Critical appraisal of four IL-6 immunoassays.

    Directory of Open Access Journals (Sweden)

    Dana K Thompson

    Full Text Available Interleukin-6 (IL-6 contributes to numerous inflammatory, metabolic, and physiologic pathways of disease. We evaluated four IL-6 immunoassays in order to identify a reliable assay for studies of metabolic and physical function. Serial plasma samples from intravenous glucose tolerance tests (IVGTTs, with expected rises in IL-6 concentrations, were used to test the face validity of the various assays.IVGTTs, administered to 14 subjects, were performed with a single infusion of glucose (0.3 g/kg body mass at time zero, a single infusion of insulin (0.025 U/kg body mass at 20 minutes, and frequent blood collection from time zero to 180 minutes for subsequent Il-6 measurement. The performance metrics of four IL-6 detection methods were compared: Meso Scale Discovery immunoassay (MSD, an Invitrogen Luminex bead-based multiplex panel (LX, an Invitrogen Ultrasensitive Luminex bead-based singleplex assay (ULX, and R&D High Sensitivity ELISA (R&D. IL-6 concentrations measured with MSD, R&D and ULX correlated with each other (Pearson Correlation Coefficients r = 0.47-0.94, p<0.0001 but only ULX correlated (r = 0.31, p = 0.0027 with Invitrogen Luminex. MSD, R&D, and ULX, but not LX, detected increases in IL-6 in response to glucose. All plasma samples were measurable by MSD, while 35%, 1%, and 4.3% of samples were out of range when measured by LX, ULX, and R&D, respectively. Based on representative data from the MSD assay, baseline plasma IL-6 (0.90 ± 0.48 pg/mL increased significantly as expected by 90 minutes (1.29 ± 0.59 pg/mL, p = 0.049, and continued rising through 3 hours (4.25 ± 3.67 pg/mL, p = 0.0048.This study established the face validity of IL-6 measurement by MSD, R&D, and ULX but not LX, and the superiority of MSD with respect to dynamic range. Plasma IL-6 concentrations increase in response to glucose and insulin, consistent with both an early glucose-dependent response (detectable at 1-2 hours and a late insulin-dependent response

  17. Profile of IL-2, IL-4, IL-10, IFN- ? , TNF- ? and KC-like cytokines in pregnant bitches

    Directory of Open Access Journals (Sweden)

    M.A.R. Feliciano

    2014-08-01

    Full Text Available The aim of this study was to determine the profile of IL-2, IL-4, IL-10, IFN-γ, and TNF-α cytokines and KC-like cells (natural killer in pregnant bitches, unpublished values for the species. A total of 27 females of the Shi Tzu, Pug, English Bulldog and French breeds, weighing 4-20kg and aged 4-6 years were used. Blood samples were collected from bitches during the anestrous and on the 2nd, 5th, 6th, 7th and 8th week of pregnancy. Serum levels of cytokines were measured by panel MILLIPLEX MAP (CCYTO-90K, MILLIPORE, Billerica, Massachusetts, USA validated for dogs. Twenty four females showed physiological pregnancy and three bitches showed pathological pregnancy. There was no difference between cytokine values during anestrous and gestational weeks of bitches (P>0.05. However, it was possible to verify the physiological behavior of serum levels during modulation of immune response in the gestational process of animals. In animals with gestational disorders, abnormal values for IL-2, IL-4 and INF-y were noted. It was concluded that serum levels of cytokines evaluated in pregnant bitches can help the better understanding of physiological and pathological gestational processes and correlated immunology in this species.

  18. Inhibition of IL-1 Signaling by Antisense Oligonucleotide-mediated Exon Skipping of IL-1 Receptor Accessory Protein (IL-1RAcP

    Directory of Open Access Journals (Sweden)

    A Seda Yılmaz-Eliş

    2013-01-01

    Full Text Available The cytokine interleukin 1(IL-1 initiates a wide range of proinflammatory cascades and its inhibition has been shown to decrease inflammation in a variety of diseases. IL-1 receptor accessory protein (IL-1RAcP is an indispensible part of the IL-1R complex that stabilizes IL-1/IL-1R interaction and plays an important role in the signal transduction of the receptor complex. The soluble form of IL-1RAcP (sIL-1RAcP contains only the extracellular domain and serves as a natural inhibitor of IL-1 signaling. Therefore, increasing sIL-1RAcP levels might be an attractive therapeutic strategy to inhibit IL-1–driven inflammation. To achieve this we designed specific antisense oligonucleotides (AON, to redirect pre-mRNA IL-1RAcP splicing by skipping of the transmembrane domain encoding exon 9. This would give rise to a novel Δ9IL-1RAcP mRNA encoding a soluble, secreted form of IL-1RAcP, which might have similar activity as natural sIL-1RAcP. AON treatment resulted in exon 9 skipping both in vitro and in vivo. A single dose injection of 10 mg AON/kg body weight induced 90% skipping in mouse liver during at least 5 days. The truncated mRNA encoded for a secreted, soluble Δ9IL-1RAcP protein. IL-1RAcP skipping resulted in a substantial inhibition of IL-1 signaling in vitro. These results indicate that skipping of the transmembrane encoding exon 9 of IL-1RAcP using specific AONs might be a promising therapeutic strategy in a variety of chronic inflammatory diseases.

  19. Inhibition of IL-1 Signaling by Antisense Oligonucleotide-mediated Exon Skipping of IL-1 Receptor Accessory Protein (IL-1RAcP)

    Science.gov (United States)

    Yılmaz-Eliş, A Seda; Aartsma-Rus, Annemieke; ‘t Hoen, Peter AC; Safdar, Huma; Breukel, Cor; van Vlijmen, Bart JM; van Deutekom, Judith; de Kimpe, Sjef; van Ommen, Gert-Jan; Verbeek, J Sjef

    2013-01-01

    The cytokine interleukin 1(IL-1) initiates a wide range of proinflammatory cascades and its inhibition has been shown to decrease inflammation in a variety of diseases. IL-1 receptor accessory protein (IL-1RAcP) is an indispensible part of the IL-1R complex that stabilizes IL-1/IL-1R interaction and plays an important role in the signal transduction of the receptor complex. The soluble form of IL-1RAcP (sIL-1RAcP) contains only the extracellular domain and serves as a natural inhibitor of IL-1 signaling. Therefore, increasing sIL-1RAcP levels might be an attractive therapeutic strategy to inhibit IL-1–driven inflammation. To achieve this we designed specific antisense oligonucleotides (AON), to redirect pre-mRNA IL-1RAcP splicing by skipping of the transmembrane domain encoding exon 9. This would give rise to a novel Δ9IL-1RAcP mRNA encoding a soluble, secreted form of IL-1RAcP, which might have similar activity as natural sIL-1RAcP. AON treatment resulted in exon 9 skipping both in vitro and in vivo. A single dose injection of 10 mg AON/kg body weight induced 90% skipping in mouse liver during at least 5 days. The truncated mRNA encoded for a secreted, soluble Δ9IL-1RAcP protein. IL-1RAcP skipping resulted in a substantial inhibition of IL-1 signaling in vitro. These results indicate that skipping of the transmembrane encoding exon 9 of IL-1RAcP using specific AONs might be a promising therapeutic strategy in a variety of chronic inflammatory diseases. PMID:23340324

  20. Modulation of pulmonary fibrosis by IL-13Rα2.

    Science.gov (United States)

    Lumsden, Robert V; Worrell, Julie C; Boylan, Denise; Walsh, Sinead M; Cramton, Jennifer; Counihan, Ian; O'Beirne, Sarah; Medina, Maria Fe; Gauldie, Jack; Fabre, Aurelie; Donnelly, Seamas C; Kane, Rosemary; Keane, Michael P

    2015-04-01

    Pulmonary fibrosis is a progressive and fatal disease that involves the remodeling of the distal airspace and the lung parenchyma, which results in compromised gas exchange. The median survival time once diagnosed is less than three years. Interleukin (IL)-13 has been shown to play a role in a number of inflammatory and fibrotic diseases. IL-13 modulates its effector functions via a complex receptor system that includes the IL-4 receptor (R) α, IL-13Rα1, and the IL-13Rα2. IL-13Rα1 binds IL-13 with low affinity, yet, when it forms a complex with IL-4α, it binds with much higher affinity, inducing the effector functions of IL-13. IL-13Rα2 binds IL-13 with high affinity but has a short cytoplasmic tail and has been shown to act as a nonsignaling decoy receptor. Transfection of fibroblasts and epithelial cells with IL-13Rα2 inhibited the IL-13 induction of soluble collagen, TGF-β, and CCL17. Adenoviral overexpression of IL-13Rα2 in the lung reduced bleomycin-induced fibrosis. Our work shows that overexpression of IL-13Rα2 inhibits the IL-13 induction of fibrotic markers in vitro and inhibits bleomycin-induced pulmonary fibrosis. In summary our study highlights the antifibrotic nature of IL-13Ra2. Copyright © 2015 the American Physiological Society.

  1. Endogenous IL-1 in cognitive function and anxiety: a study in IL-1RI-/- mice.

    Directory of Open Access Journals (Sweden)

    Carol L Murray

    Full Text Available Interleukin-1 (IL-1 is a key pro-inflammatory cytokine, produced predominantly by peripheral immune cells but also by glia and some neuronal populations within the brain. Its signalling is mediated via the binding of IL-1α or IL-1β to the interleukin-1 type one receptor (IL-1RI. IL-1 plays a key role in inflammation-induced sickness behaviour, resulting in depressed locomotor activity, decreased exploration, reduced food and water intake and acute cognitive deficits. Conversely, IL-1 has also been suggested to facilitate hippocampal-dependent learning and memory: IL-1RI(-/- mice have been reported to show deficits on tasks of visuospatial learning and memory. We sought to investigate whether there is a generalised hippocampal deficit in IL-1RI(-/- animals. Therefore, in the current study we compared wildtype (WT mice to IL-1RI(-/- mice using a variety of hippocampal-dependent learning and memory tasks, as well as tests of anxiety and locomotor activity. We found no difference in performance of the IL-1RI(-/- mice compared to WT mice in a T-maze working memory task. In addition, the IL-1RI(-/- mice showed normal learning in various spatial reference memory tasks including the Y-maze and Morris mater maze, although there was a subtle deficit in choice behaviour in a spatial discrimination, beacon watermaze task. IL-1RI(-/- mice also showed normal memory for visuospatial context in the contextual fear conditioning paradigm. In the open field, IL-1RI(-/- mice showed a significant increase in distance travelled and rearing behaviour compared to the WT mice and in the elevated plus-maze spent more time in the open arms than did the WT animals. The data suggest that, contrary to prior studies, IL-1RI(-/- mice are not robustly impaired on hippocampal-dependent memory and learning but do display open field hyperactivity and decreased anxiety compared to WT mice. The results argue for a careful evaluation of the roles of endogenous IL-1 in hippocampal

  2. IL-18 paradox in pancreatic carcinoma: elevated serum levels of free IL-18 are correlated with poor survival.

    Science.gov (United States)

    Carbone, Anna; Vizio, Barbara; Novarino, Anna; Mauri, Francesco Angelo; Geuna, Massimo; Robino, Carlo; Brondino, Gabriele; Prati, Adriana; Giacobino, Alice; Campra, Donata; Chiarle, Roberto; Fronda, Gian Ruggero; Ciuffreda, Libero; Bellone, Graziella

    2009-01-01

    The role of the proinflammatory interleukin (IL)-18 in cancer progression remains controversial; we thus examined the hypothesis that impaired antitumor immune response in pancreatic carcinoma patients is related to elevated levels of its natural inhibitor IL-18 binding protein (BP) and/or to alteration in the IL-18 receptor complex expression and function. IL-18 and IL-18 binding protein isoform a (BPa) was assessed in pancreatic carcinoma patients at various disease stages, and after surgery/chemotherapy; free bioactive IL-18 concentrations were calculated. IL-18 receptor complex expression in lymphocyte subsets was analyzed and signaling function was assessed versus healthy donors. Carcinoma cells exhibited below normal IL-18BPa expression and above normal IL-18 expression. Circulating IL-18BPa and IL-18 were above controls. Unexpectedly, free unbound IL-18 serum levels were correlated with disease severity and poor survival. IL-18BPa levels were unchanged by surgery but free IL-18 levels were elevated. Gemcitabine with 5-fluorouracil or oxaliplatin, but not alone, increased IL-18 and free IL-18 levels statistically significantly, without affecting IL-18BPa. Spontaneous/induced IL-18 receptor alpha and receptor beta expression in peripheral blood lymphocyte subsets from patients with advanced disease were near-normal, although CD4+ and CD8+ cells were fewer in percentage, and fully functional in inducing interferon-gamma. IL-18 is proposed as novel adjuvant cancer therapy, but free IL-18 levels are increased in the blood of pancreatic carcinoma patients, despite elevated IL-18BP levels, and are associated with poor survival; this highlights recent experimental insights into the prometastatic and proangiogenic effects of IL-18, and suggests that careful preclinical studies are needed to determine the proper application of IL-18 in cancer therapy.

  3. Three-Dimensional Conformal Radiotherapy in Prostate Cancer Patients: Rise in Interleukin 6 (IL-6) but not IL-2, IL-4, IL-5, Tumor Necrosis Factor-{alpha}, MIP-1-{alpha}, and LIF Levels

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira Lopes, Carlos [Universidade do Vale do Paraiba, Centro de Oncologia Radioterapica do Vale do Paraiba, Universidade do Vale do Paraiba Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraiba, Sao Jose dos Campos, Sao Paulo (Brazil); Callera, Fernando, E-mail: fcallera@gmail.com [Centro de Hematologia Onco-hematologia e Transplantes de Medula Ossea do Vale do Paraiba, Sao Paulo (Brazil)

    2012-03-15

    Purpose: To investigate the effect of radiotherapy (RT) on serum levels of interleukin-2 (IL-2), IL-4, IL-5, IL-6, tumor necrosis factor alpha (TNF-{alpha}), macrophage inflammatory protein-1-alpha (MIP-1-{alpha}) and leukemia inhibitory factor (LIF) in patients with prostate cancer. Methods and Materials: Forty eight patients with prostate cancer received three-dimensional conformal blocking radiation therapy with a linear accelerator. IL-2, IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were measured by the related immunoassay kit 1 day before the beginning of RT and during RT at days 15 and 30. Results: The mean IL-2 values were elevated before and during the RT in contrast with those of IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF, which were within the normal range under the same conditions. Regarding markers IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF, comparisons among the three groups (before treatment and 15 and 30 days during RT) did not show significant differences. Although values were within the normal range, there was a significant rise in IL-6 levels at day 15 of RT (p = 0.0049) and a decline at day 30 to levels that were similar to those observed before RT. Conclusions: IL-6 appeared to peak after 15 days of RT before returning to pre-RT levels. In contrast, IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were not sensitive to irradiation. The increased levels of IL-6 following RT without the concurrent elevation of other cytokines involved in the acute phase reaction did not suggest a classical inflammatory response to radiation exposure. Further studies should be designed to elucidate the role of IL-6 levels in patients with prostate cancer treated with RT.

  4. Andrographolide presents therapeutic effect on ulcerative colitis through the inhibition of IL-23/IL-17 axis.

    Science.gov (United States)

    Zhu, Qin; Zheng, Peifen; Chen, Xinyu; Zhou, Feng; He, Qiaona; Yang, Yuefeng

    2018-01-01

    Ulcerative colitis (UC) is a chronic and nonspecific intestinal inflammatory disease, which may increase the risk of colon cancer. Andrographolide is a main active component of Andrographis paniculata . The anti-inflammatory ability of andrographolide suggested its potential therapeutic effect against UC. In the present study, elevated serum concentrations of proinflammatory factors, including (TNF)-α, interleukin (IL)-1β, IL-6 and IL-23, as well as increased percentages of Th17 cells (IL-17+CD4+ cells) in CD4+ cells were detected in UC patients compared to that in healthy donors. These data suggested that Th17 immune responses may involve in the pathogenesis of UC. Experimental colitis mouse model was then established. The results of hematoxylin and eosin staining demonstrated the therapeutic effect of andrographolide on colitis. Enzyme-linked immunosorbent assay (ELISA), flow cytometry and western blotting analyses showed that andrographolide could decreased the levels of proinflammatory factors TNF-α, IL-1β, IL-6 and IL-17A in the serum and in the colon tissues, reduced the percentages of Th17 cells in CD4+ cells, and suppressed the levels of IL-23, IL-17A, ROR-γt (key transcription factor of Th17 cells) and p-STAT3 in the colon tissues. Further, peripheral blood mononuclear cells (PBMCs) were isolated from UC patients and treated with various concentrations of andrographolide (0, 10, 20 and 30 μg/ml). Andrographolide also showed inhibitory effects on the levels of proinflammatory factors, the percentages of Th17 cells and the expression of relative proteins. Similar results were obtained in lipopolysaccharide-treated normal PBMCs. These data suggested that andrographolide may inhibit Th17 immune response via STAT3 signaling. In conclusion, we demonstrated that andrographolide inhibited the activity of IL-23/IL-17 axis and down-stream pro-inflammatory factors so as to suppress inflammation response, resulting in the relieving of UC.

  5. A Brief History of IL-1 and IL-1 Ra in Rheumatology

    Directory of Open Access Journals (Sweden)

    Jean-Michel Dayer

    2017-05-01

    Full Text Available The history of what, in 1979, was called interleukin-1 (IL-1, orchestrator of leukocyte inter-communication, began many years before then, initially by the observation of fever induction via the endogenous pyrogen (EP (1974 and then in rheumatology on the role in tissue destruction in rheumatoid diseases via the induction of collagenase and PGE2 in human synovial cells by a mononuclear cell factor (MCF (1977. Since then, the family has exploded to presently 11 members as well as many membrane-bound and soluble receptor forms. The discovery of a natural Interleukin-1 receptor antagonist (IL-1Ra in human biological fluids has highlighted the importance of IL-1 and IL-1Ra in human diseases. Evidence delineating its role in autoinflammatory syndromes and the elucidation of the macromolecular complex referred to as “inflammasome” have been instrumental to our understanding of the link with IL-1. At present, the IL-1blockade as therapeutic approach is crucial for many hereditary autoinflammatory diseases, as well as for adult-onset Still’s disease, crystal-induced arthropathies, certain skin diseases including neutrophil-triggered skin diseases, Behçet’s disease and deficiency of IL-1Ra and other rare fever syndromes. Its role is only marginally important in rheumatoid arthritis and is still under debate with regard to osteoarthritis, type 2 diabetes mellitus, cardiovascular diseases and cancer. This brief historical review focuses on some aspects of IL-1, mainly IL-1β and IL-Ra, in rheumatology. There are many excellent reviews focusing on the IL-1 family in general or with regard to specific diseases or biological discoveries.

  6. Purification, crystallization and preliminary X-ray diffraction analysis of the IL-20-IL-20R1-IL-20R2 complex

    Energy Technology Data Exchange (ETDEWEB)

    Logsdon, Naomi J.; Allen, Christopher E.; Rajashankar, Kanagalaghatta R.; Walter, Mark R. (Cornell); (UAB)

    2012-02-08

    Interleukin-20 (IL-20) is an IL-10-family cytokine that regulates innate and adaptive immunity in skin and other tissues. In addition to protecting the host from various external pathogens, dysregulated IL-20 signaling has been shown to contribute to the pathogenesis of human psoriasis. IL-20 signals through two cell-surface receptor heterodimers, IL-20R1-IL-20R2 and IL-22R1-IL-20R2. In this report, crystals of the IL-20-IL-20R1-IL-20R2 ternary complex have been grown from polyethylene glycol solutions. The crystals belonged to space group P4{sub 1}2{sub 1}2 or P4{sub 3}2{sub 1}2, with unit-cell parameters a = 111, c = 135 {angstrom}, and diffracted X-rays to 3 {angstrom} resolution. The crystallographic asymmetric unit contains one IL-20-IL-20R1-IL-20R2 complex, corresponding to a solvent content of approximately 54%.

  7. Critical analysis of the special wastes register: the case of the province of Trento; Analisi critica del catasto dei rifiuti speciali: il caso della provincia di Trento

    Energy Technology Data Exchange (ETDEWEB)

    Mattolin, P.; Ragazzi, M.; Andreottola, G. [Trento Univ. (Italy). Dip. di Ingegneria Civile e Ambientale

    1998-09-01

    notevoli sovra o sottostime della produzione stessa. La Provincia Autonoma di Trento ha provveduto a creare un archivio informatizzato dei dati del Catasto dei Rifiuti Speciali a partire dal 1989 ed ha messo a disposizione dell`Universita` di Trento una serie storica di sei anni per svolgere delle elaborazioni sulla variabilita` della produzione e sull`affidabilita` del metodo di stima che utilizza il coefficiente specifico per addetto. L`analisi del metodo di stima che utilizza il coefficiente specifico per addetto ha evidenziato una forte variabilita` del coefficiente sia nel tempo sia per classe dimensionale delle unita` locali. Tale variabilita` e` imputabile ai limiti estrinseci del coefficiente specifico cosi` definito. L`applicazione, quindi, del coefficiente specifico per addetto per effettuare una stima della produzione deve essere fatta con cautela, soprattutto se in tempi diversi dall`anno in cui e` stato calcolato il coefficiente. Tale parametro puo` costituire, pero` un utile strumento in fase di controllo e verifica dei dati.

  8. IL-7 Induces an Epitope Masking of γc Protein in IL-7 Receptor Signaling Complex

    Directory of Open Access Journals (Sweden)

    Tae Sik Goh

    2017-01-01

    Full Text Available IL-7 signaling via IL-7Rα and common γ-chain (γc is necessary for the development and homeostasis of T cells. Although the delicate mechanism in which IL-7Rα downregulation allows the homeostasis of T cell with limited IL-7 has been well known, the exact mechanism behind the interaction between IL-7Rα and γc in the absence or presence of IL-7 remains unclear. Additionally, we are still uncertain as to how only IL-7Rα is separately downregulated by the binding of IL-7 from the IL-7Rα/γc complex. We demonstrate here that 4G3, TUGm2, and 3E12 epitope masking of γc protein are induced in the presence of IL-7, indicating that the epitope alteration is induced by IL-7 binding to the preassembled receptor core. Moreover, the epitope masking of γc protein is inversely correlated with the expression of IL-7Rα upon IL-7 binding, implying that the structural alteration of γc might be involved in the regulation of IL-7Rα expression. The conformational change in γc upon IL-7 binding may contribute not only to forming the functional IL-7 signaling complex but also to optimally regulating the expression of IL-7Rα.

  9. IL-7 Induces an Epitope Masking of γc Protein in IL-7 Receptor Signaling Complex

    Science.gov (United States)

    Goh, Tae Sik; Jo, Yuna; Lee, Byunghyuk; Kim, Geona; Hwang, Hyunju; Ko, Eunhee; Kang, Seung Wan; Oh, Sae-Ock; Baek, Sun-Yong; Yoon, Sik; Lee, Jung Sub

    2017-01-01

    IL-7 signaling via IL-7Rα and common γ-chain (γc) is necessary for the development and homeostasis of T cells. Although the delicate mechanism in which IL-7Rα downregulation allows the homeostasis of T cell with limited IL-7 has been well known, the exact mechanism behind the interaction between IL-7Rα and γc in the absence or presence of IL-7 remains unclear. Additionally, we are still uncertain as to how only IL-7Rα is separately downregulated by the binding of IL-7 from the IL-7Rα/γc complex. We demonstrate here that 4G3, TUGm2, and 3E12 epitope masking of γc protein are induced in the presence of IL-7, indicating that the epitope alteration is induced by IL-7 binding to the preassembled receptor core. Moreover, the epitope masking of γc protein is inversely correlated with the expression of IL-7Rα upon IL-7 binding, implying that the structural alteration of γc might be involved in the regulation of IL-7Rα expression. The conformational change in γc upon IL-7 binding may contribute not only to forming the functional IL-7 signaling complex but also to optimally regulating the expression of IL-7Rα. PMID:28127156

  10. High salt reduces the activation of IL-4- and IL-13-stimulated macrophages.

    Science.gov (United States)

    Binger, Katrina J; Gebhardt, Matthias; Heinig, Matthias; Rintisch, Carola; Schroeder, Agnes; Neuhofer, Wolfgang; Hilgers, Karl; Manzel, Arndt; Schwartz, Christian; Kleinewietfeld, Markus; Voelkl, Jakob; Schatz, Valentin; Linker, Ralf A; Lang, Florian; Voehringer, David; Wright, Mark D; Hubner, Norbert; Dechend, Ralf; Jantsch, Jonathan; Titze, Jens; Müller, Dominik N

    2015-11-02

    A high intake of dietary salt (NaCl) has been implicated in the development of hypertension, chronic inflammation, and autoimmune diseases. We have recently shown that salt has a proinflammatory effect and boosts the activation of Th17 cells and the activation of classical, LPS-induced macrophages (M1). Here, we examined how the activation of alternative (M2) macrophages is affected by salt. In stark contrast to Th17 cells and M1 macrophages, high salt blunted the alternative activation of BM-derived mouse macrophages stimulated with IL-4 and IL-13, M(IL-4+IL-13) macrophages. Salt-induced reduction of M(IL-4+IL-13) activation was not associated with increased polarization toward a proinflammatory M1 phenotype. In vitro, high salt decreased the ability of M(IL-4+IL-13) macrophages to suppress effector T cell proliferation. Moreover, mice fed a high salt diet exhibited reduced M2 activation following chitin injection and delayed wound healing compared with control animals. We further identified a high salt-induced reduction in glycolysis and mitochondrial metabolic output, coupled with blunted AKT and mTOR signaling, which indicates a mechanism by which NaCl inhibits full M2 macrophage activation. Collectively, this study provides evidence that high salt reduces noninflammatory innate immune cell activation and may thus lead to an overall imbalance in immune homeostasis.

  11. Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease-like pathology and cognitive decline.

    Science.gov (United States)

    Vom Berg, Johannes; Prokop, Stefan; Miller, Kelly R; Obst, Juliane; Kälin, Roland E; Lopategui-Cabezas, Ileana; Wegner, Anja; Mair, Florian; Schipke, Carola G; Peters, Oliver; Winter, York; Becher, Burkhard; Heppner, Frank L

    2012-12-01

    The pathology of Alzheimer's disease has an inflammatory component that is characterized by upregulation of proinflammatory cytokines, particularly in response to amyloid-β (Aβ). Using the APPPS1 Alzheimer's disease mouse model, we found increased production of the common interleukin-12 (IL-12) and IL-23 subunit p40 by microglia. Genetic ablation of the IL-12/IL-23 signaling molecules p40, p35 or p19, in which deficiency of p40 or its receptor complex had the strongest effect, resulted in decreased cerebral amyloid load. Although deletion of IL-12/IL-23 signaling from the radiation-resistant glial compartment of the brain was most efficient in mitigating cerebral amyloidosis, peripheral administration of a neutralizing p40-specific antibody likewise resulted in a reduction of cerebral amyloid load in APPPS1 mice. Furthermore, intracerebroventricular delivery of antibodies to p40 significantly reduced the concentration of soluble Aβ species and reversed cognitive deficits in aged APPPS1 mice. The concentration of p40 was also increased in the cerebrospinal fluid of subjects with Alzheimer's disease, which suggests that inhibition of the IL-12/IL-23 pathway may attenuate Alzheimer's disease pathology and cognitive deficits.

  12. Interleukin (IL)-17A and IL-17F and asthma in Saudi Arabia: mRNA ...

    African Journals Online (AJOL)

    Interleukin (IL)-17A and IL-17F and asthma in Saudi Arabia: mRNA transcript levels and gene polymorphisms. MD Bazzi, MA Sultan, N Al Tassan, M Alanazi, A Al-Amri, MS Al-Hajjaj, S Al-muhsen, K Alba-Concepcion, A Warsy ...

  13. Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis

    NARCIS (Netherlands)

    Festen, E. A. M.; Goyette, P.; Scott, R.; Annese, V.; Zhernakova, A.; Lian, J.; Lefebvre, C.; Brant, S. R.; Cho, J. H.; Silverberg, M. S.; Taylor, K. D.; de Jong, D. J.; Stokkers, P. C.; Mcgovern, D.; Palmieri, O.; Achkar, J-P; Xavier, R. J.; Daly, M. J.; Duerr, R. H.; Wijmenga, C.; Weersma, R. K.; Rioux, J. D.

    Objectives: Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac

  14. Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis

    NARCIS (Netherlands)

    Festen, E.A.M.; Goyette, P.; Scott, R.; Annese, V.; Zhernakova, A.; Lian, J.; Lefèbvre, C.; Brant, S.R.; Cho, J.H.; Silverberg, M.S.; Taylor, K.D.; de Jong, D.J.; Stokkers, P.C.; Mcgovern, D.; Palmieri, O.; Achkar, J.P.; Xavier, R.J.; Daly, M.J.; Duerr, R.H.; Wijmenga, C.; Weersma, R.K.; Rioux, J.D.

    2009-01-01

    Objectives: Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac

  15. Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis

    NARCIS (Netherlands)

    Festen, E. A. M.; Goyette, P.; Scott, R.; Annese, V.; Zhernakova, A.; Lian, J.; Lefèbvre, C.; Brant, S. R.; Cho, J. H.; Silverberg, M. S.; Taylor, K. D.; de Jong, D. J.; Stokkers, P. C.; Mcgovern, D.; Palmieri, O.; Achkar, J.-P.; Xavier, R. J.; Daly, M. J.; Duerr, R. H.; Wijmenga, C.; Weersma, R. K.; Rioux, J. D.

    2009-01-01

    Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac disease, type 1

  16. Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis.

    NARCIS (Netherlands)

    Festen, E.A.; Goyette, P.; Scott, R.; Annese, V.; Zhernakova, A.; Lian, J.; Lefebvre, C.; Brant, S.R.; Cho, J.H.; Silverberg, M.S.; Taylor, K.D.; Jong, D.J. de; Stokkers, P.C.; Mcgovern, D.; Palmieri, O.; Achkar, J.P.; Xavier, R.J.; Daly, M.J.; Duerr, R.H.; Wijmenga, C.; Weersma, R.K.; Rioux, J.D.

    2009-01-01

    OBJECTIVES: Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac

  17. Diagnostic significance of IL-6 and IL-8 in tubal ectopic pregnancy.

    Science.gov (United States)

    Rajendiran, Soundravally; Senthil Kumar, G P; Nimesh, Archana; Dhiman, Pooja; Shivaraman, K; Soundararaghavan, S

    2016-10-01

    As there are no specific non-invasive markers for the diagnosis of tubal ectopic pregnancy, our objective in the present study was to explore the role of inflammatory cytokines IL-6 and IL-8 in the diagnosis of ruptured tubal ectopic pregnancy. Twenty-eight women with tubal ectopic pregnancy, 31 patients with intrauterine abortion and 29 gestational age matched women having normal intrauterine pregnancy were included in the study. Five millilitre of blood was collected at the time of admission, serum was separated and stored at -70 °C for subsequent analysis of β hCG, IL-6 and IL-8 levels. The level of IL-6 was a significant increase in the women with tubal ectopic pregnancy compared to intrauterine abortion and normal pregnancy. IL-8 levels decrease significantly in the tubal ectopic pregnancy and in intrauterine abortion patients when compared with the normal pregnancy group. At the cutoff of 26.48 pg/ml IL-6 level predicted the tubal ectopic pregnancy with moderate accuracy. Therefore, it can be concluded that measurement of IL-6 may have relevance in the diagnosis of ectopic pregnancy as a novel inflammatory serum biomarkers.

  18. Cocaine abuse and effects in the serum levels of cytokines IL-6 and IL-10.

    Science.gov (United States)

    Moreira, Fernanda Pedrotti; Medeiros, João Ricardo Carvalho; Lhullier, Alfredo Cardoso; Souza, Luciano Dias de Mattos; Jansen, Karen; Portela, Luis Valmor; Lara, Diogo R; da Silva, Ricardo Azevedo; Wiener, Carolina David; Oses, Jean Pierre

    2016-01-01

    Cocaine abuse is capable of activating the innate immune system in the CNS resulting in deregulation of homeostasis between pro and antiinflammatory cytokines. The aim of this study was to investigate serum levels of pro and antiinflammatory cytokines, IL-6 and IL-10 respectively, in cocaine users from a young population-based sample. This is a case-control study nested in a cross-sectional population-based survey, with individuals of 18 and 35 years old. Two groups were selected: 24 healthy controls and 12 subjects who reported cocaine use. Serum IL-6 and IL-10 were measured by ELISA using a commercial kit. There was a statistically significant increase in IL-6 (p=0.037) and decrease in IL-10 (p=0.007) serum levels, between cocaine users and the control group. There was also an increase in the ratio IL-6/IL-10 (p=0.013) among cocaine users individuals, when compared to the control group. Our results suggest that cocaine users showed an activation of the immune system when compared a control group, demonstrating a disruption in the balance of pro and antiinflammatory cytokines. Thus, peripheral cytokines may represent a putative biomarkers for cocaine users, contributing to the development of diagnosis and effective treatments. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Fundamentos del metodo cientifico

    Directory of Open Access Journals (Sweden)

    Badii, M. H.

    2004-01-01

    Full Text Available El objetivo de esta obra no radica en realizar una búsqueda exhaustiva de la literatura en el tema, sino, sentar las bases del método científico, notando los aspectos filosóficos e éticos de la ciencia. Se presentan los conceptos y definiciones fundamentales relacionados con la metodología de la investigación científica. Se maneja el concepto de la toma de los datos válidos como un requisito básico en cualquier trabajo científico. Se pone a disposición del lector un modelo denominado el ECOEE que es una herramienta poderosa para establecer puntos de comparación e discusión entre los resultados de diferentes trabajos científicos. Finalmente, ofrece unas sugerencias de que hacer o no hacer en cuanto a realizar un trabajo de investigación.

  20. Signaling through IL-17C/IL-17RE is dispensable for immunity to systemic, oral and cutaneous candidiasis.

    Science.gov (United States)

    Conti, Heather R; Whibley, Natasha; Coleman, Bianca M; Garg, Abhishek V; Jaycox, Jillian R; Gaffen, Sarah L

    2015-01-01

    Candida albicans is a commensal fungal microbe of the human orogastrointestinal tract and skin. C. albicans causes multiple forms of disease in immunocompromised patients, including oral, vaginal, dermal and disseminated candidiasis. The cytokine IL-17 (IL-17A) and its receptor subunits, IL-17RA and IL-17RC, are required for protection to most forms of candidiasis. The importance of the IL-17R pathway has been observed not only in knockout mouse models, but also in humans with rare genetic mutations that impact generation of Th17 cells or the IL-17 signaling pathway, including Hyper-IgE Syndrome (STAT3 or TYK2 mutations) or IL17RA or ACT1 gene deficiency. The IL-17 family of cytokines is a distinct subclass of cytokines with unique structural and signaling properties. IL-17A is the best-characterized member of the IL-17 family to date, but far less is known about other IL-17-related cytokines. In this study, we sought to determine the role of a related IL-17 cytokine, IL-17C, in protection against oral, dermal and disseminated forms of C. albicans infection. IL-17C signals through a heterodimeric receptor composed of the IL-17RA and IL-17RE subunits. We observed that IL-17C mRNA was induced following oral C. albicans infection. However, mice lacking IL-17C or IL-17RE cleared C. albicans infections in the oral mucosa, skin and bloodstream at rates similar to WT littermate controls. Moreover, these mice demonstrated similar gene transcription profiles and recovery kinetics as WT animals. These findings indicate that IL-17C and IL-17RE are dispensable for immunity to the forms of candidiasis evaluated, and illustrate a surprisingly limited specificity of the IL-17 family of cytokines with respect to systemic, oral and cutaneous Candida infections.

  1. 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...

  2. Il Rapporto Radcliff: e l'odierna politica monetaria inglese.

    Directory of Open Access Journals (Sweden)

    R.S. SAYERS

    2014-11-01

    Full Text Available Il saggio si occupa di tre principali argomenti ai quali il comitato ha dedicato tanta attenzione nel suo rapporto. Essi sono: il problema dell’informazione sulle questioni finanziarie, il controllo della quantità di moneta e la politica del tasso di interesse. C’è poi una breve sezione dedicata al problema costituzionale della posizione della banca centrale.

  3. Endogenous IL-10 protects mice from death during septic peritonitis

    NARCIS (Netherlands)

    van der Poll, T.; Marchant, A.; Buurman, W. A.; Berman, L.; Keogh, C. V.; Lazarus, D. D.; Nguyen, L.; Goldman, M.; Moldawer, L. L.; Lowry, S. F.

    1995-01-01

    IL-10 production during endotoxic shock is part of a protective mechanism that involves IL-10-induced inhibition of TNF synthesis. We sought to determine the role of IL-10 in septic peritonitis induced by cecal ligation and puncture (CLP). CLP led to a rapid induction of IL-10 mRNA in various organs

  4. 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....

  5. Anti-IL-1alpha autoantibodies in early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Forslind, K; Svensson, Birte; Svenson, M

    2001-01-01

    To investigate the potential predictive value of autoantibodies against IL1-alpha (anti-IL-1alpha) in patients with early rheumatoid arthritis (RA).......To investigate the potential predictive value of autoantibodies against IL1-alpha (anti-IL-1alpha) in patients with early rheumatoid arthritis (RA)....

  6. Le Nuove Scienze e il Genius Loci

    Directory of Open Access Journals (Sweden)

    Michael Mehaffy

    2009-12-01

    Full Text Available Oggi la teoria della conservazione urbana sta affrontando aspetti intangibili – notabilmente il concetto del “genius loci”. Ma questa idea potenzialmente vaga deve essere compresa nei termini che permettono un suo effettivo utilizzo. L’autore argomenta che tale questione può essere affrontata attraverso un approfondimento della complessità della scienza rivelando i modi attraverso i quali un sistema nella sua interezza può essere scomposto in elementi dinamici. All’interno dei tessuti storici noi siamo conservatori, siamo utilizzatori, siamo consumatori e, inevitabilmente, siamo coloro che attuano le modifiche. Il nostro compito non è di far resistere quell’insieme, ma di poterlo gestire in maniera più dinamica e di pretendere un più ampio concetto di conservazione. Questo atteggiamento va oltre il dualismo basato sul modello di pensiero del “genius loci” ma abbraccia una più efficace aspettativa di crescita organica.

  7. Il rumore elettrico Dalla fisica alla progettazione

    CERN Document Server

    Pallottino, Giovanni Vittorio

    2011-01-01

    L’opera fornisce una trattazione chiara, agile ed essenziale, ma completa, del rumore elettrico, argomento considerato generalmente oscuro e specialistico. Molto più breve (circa 275mila battute) dei testi attualmente disponibili. Il contenuto copre gli aspetti essenziali della matematica e della fisica del rumore (termico, shot. 1/f, …), e della sua rappresentazione nei circuiti. Discute quindi il rumore nei dispositivi passivi e attivi, e introduce i criteri di progettazione a basso rumore. Affronta infine brevemente questioni quali l’estrazione del segnale dal rumore e gli impieghi utili del rumore. L’attenzione è generalmente rivolta alla strumentazione fisica a bassa frequenza, in relazione alla pluridecennale esperienza specifica dell’autore. Si tratta di una estensione delle dispense, utilizzate per anni, di un corso universitario. Pertanto la trattazione è fortemente didattica, con particolare attenzione a rimuovere ambiguità e incertezze, discutendo il materiale in termini fisici intuit...

  8. IL17eScan: A Tool for the Identification of Peptides Inducing IL-17 Response

    Directory of Open Access Journals (Sweden)

    Sudheer Gupta

    2017-10-01

    Full Text Available IL-17 cytokines are pro-inflammatory cytokines and are crucial in host defense against various microbes. Induction of these cytokines by microbial antigens has been investigated in the case of ischemic brain injury, gingivitis, candidiasis, autoimmune myocarditis, etc. In this study, we have investigated the ability of amino acid sequence of antigens to induce IL-17 response using machine-learning approaches. A total of 338 IL-17-inducing and 984 IL-17 non-inducing peptides were retrieved from Immune Epitope Database. 80% of the data were randomly selected as training dataset and rest 20% as validation dataset. To predict the IL-17-inducing ability of peptides/protein antigens, different sequence-based machine-learning models were developed. The performance of support vector machine (SVM and random forest (RF was compared with different parameters to predict IL-17-inducing epitopes (IIEs. The dipeptide composition-based SVM-model displayed an accuracy of 82.4% with Matthews correlation coefficient = 0.62 at polynomial (t = 1 kernel on 10-fold cross-validation and outperformed RF. Amino acid residues Leu, Ser, Arg, Asn, and Phe and dipeptides LL, SL, LK, IL, LI, NL, LR, FK, SF, and LE are abundant in IIEs. The present tool helps in the identification of IIEs using machine-learning approaches. The induction of IL-17 plays an important role in several inflammatory diseases, and identification of such epitopes would be of great help to the immunologists. It is freely available at http://metagenomics.iiserb.ac.in/IL17eScan/ and http://metabiosys.iiserb.ac.in/IL17eScan/.

  9. Serum levels of interleukin-1 (IL-1α, IL-1β in patients with alopecia areata

    Directory of Open Access Journals (Sweden)

    Emina Kasumagić-Halilovic

    2012-07-01

    Full Text Available Introduction: Alopecia areata (AA is disease characterized by focally, nonscarring hair loss on the scalp or other parts of the body. It affects 1-2% population of both genders and occurs at all age groups. The etiology is unknown, although most evidence supports the hypothesis that AA is a T-cell-mediated autoimmune disease of the hair follicle and that cytokines play an important role.Objective: The aim of our study was to evaluate serum concentrations of IL-1α and IL-1β in patients with AA and healthy subjects and also to asses a possible association between these cytokines and duration of the disease.Methods: Forty six patients with AA and 20 healthy controls were enrolled in the study. Serum concentrations of IL-1α and IL-1β were measured using enzyme-linked immunoassay techniques.Results: The serum level of IL-1α in patients with AA was significantly higher than that in the control group (4.34±0.86 pg/mL vs 3.66±0.35 pg/mL, respectively. IL-1β levels were greater in patients with AA than in controls (2.35±0.17 pg/mL vs 2.24±0.30, respectively but the difference was not significant (p>0.05. No correlations were found between duration of disease and the serum levels of IL-1α and IL-1β.Conclusion: Our results have demonstrated the importance of determining IL-1a concentration in serum in patients with AA. This research could contribute to the interpretation of insufficiently well known views of the pathogenesis role and significance of IL-1α in AA.

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

    Science.gov (United States)

    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

  11. Playware e robotica modulare per il gioco

    Directory of Open Access Journals (Sweden)

    Henrik H. Lund

    2009-01-01

    Full Text Available In questo contributo presentiamo e usiamo il concetto di building block robotico per la creazione di playware. Il concetto tecnologico di building block programmabili e dotati di input e output (ivi inclusa la comunicazione e dell'intelligenza artificiale embodied, che enfatizza la relazione fra morfologia e controllo.Per dare un esempio concreto del concetto di building block robotico, proponiamo le mattonelle che abbiamo creato, come elementi che compongono un nuovo tipo di campo giochi sul quale i bambini possono sperimentare un feedback immediato ai loro movimenti.

  12. 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...

  13. DMPD: Differential responses of human monocytes and macrophages to IL-4 and IL-13. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10534111 Differential responses of human monocytes and macrophages to IL-4 and IL-1...):575-8. (.png) (.svg) (.html) (.csml) Show Differential responses of human monocytes and macrophages to IL-...4 and IL-13. PubmedID 10534111 Title Differential responses of human monocytes an

  14. Giordano Bruno e il Problema della Modernita

    Directory of Open Access Journals (Sweden)

    Stefano Ulliana

    2005-08-01

    Full Text Available Il testo viene pubblicato per gentile concessione della casa editrice ESI ed e’ tratto dal libro di Stefano Ulliana “Il concetto creativo e dialettico dello Spirito nei Dialoghi Italiani di Giordano Bruno. Il confronto con la tradizione neoplatonico-aristotelica: il testo bruniano De l’Infinito, Universo e mondi”, Edizioni Scientifiche Italiane, Napoli, 2003. Le argomentazioni presentate ne Il concetto creativo e dialettico dello Spirito nei Dialoghi Italiani di Giordano Bruno (Il confronto con la tradizione neoplatonico-aristotelica: il testo bruniano De l’Infinito, Universo e mondi costituiscono le conclusioni ultime e definitive di un lavoro di ricerca che ha investito l’insieme dei Dialoghi Italiani, riuscendo a reperire ed a far emergere quello che pare il nucleo più profondo ed importante—il vero e proprio elevato fondamento—della speculazione bruniana: la presenza attiva di un concetto triadico teologico-politico—il Padre, il Figlio e lo Spirito della tradizione trinitaria cristiana—però riformulato attraverso il capovolgimento rivoluzionario di questa stessa tradizione, attuato attraverso il concetto creativo e dialettico dell’infinito. In questo modo la stessa tradizione platonica pare subire una trasformazione essenziale, abbandonando qualunque forma di alienazione e negazione, per riaprirsi invece verso soluzioni che paiono riprendere moniti ed osservazioni suscitati dalle prime, grandi e maestose, speculazioni dei filosofi presocratici. Parmenide, Eraclito ed Empedocle sembrano rivivere nei testi bruniani, riproponendo una soluzione ben diversa a quei nodi e problemi teoretico-pratici—fondamentale il rapporto Uno-molti e tutto ciò che da esso consegue, sia sul piano naturale che politico—apparentemente risolti e codificati dal pensiero postsocratico, prima platonico e poi aristotelico. L’inscindibilit� del principio di libert� (la figura teologica del Padre ed eguaglianza (il Figlio, attraverso

  15. Development of an analytic method for arsenic's determination in lime and tortilla; Desarrollo de un metodo analitico para determinacion de arsenico en cal y tortilla

    Energy Technology Data Exchange (ETDEWEB)

    Huato Soberanis, Julio; Ogura, Tetsuya [Universidad Autonoma de Guadalajara, Guadalajara, Jalisco (Mexico)

    1995-02-01

    A spectrophotometric method to determine As in tortilla and lime has been optimized, modifying the AsH{sub 3} generator. The reaction between arsin (AsH{sub 3}){sub 4} and diethyldithiocarbamate of Ag (AgDDC); was followed spectrophotometrically. The conditions under which the As remains in the ash during the calcination of the tortillas were studied. It was found that when they were heated in a quartz tube with a careful control of the air flow and oxygen, as well as the heating temperature, the arsenic loss in minimized. [Spanish] Se ha optimizado el metodo para determinar As en la tortilla y cal mediante espectrometria en el visible del color producido en la reaccion entre Arsina (AsH{sub 3}){sub 4} y dietilditiocarbamato de plata (AgDDC); modificando el generador de AsH{sub 3}. Se han buscado las condiciones en las que el arsenico permanece en las cenizas de la calcinacion de las tortillas; encontrandose que las tortillas deben calentarse en un tubo de cuarzo con control del flujo de aire y oxigeno asi como de la temperatura de calentamiento.

  16. Application of the identification methods from Hilbert and Prony to the study of oscillatory phenomena in electrical power systems; Aplicacion de los metodos de identificacion de Hilbert y Prony al estudio de fenomenos oscilatorios en sistemas electricos de potencia

    Energy Technology Data Exchange (ETDEWEB)

    Andrade Soto, Manuel Antonio

    2002-10-15

    In the present thesis work the application of identification techniques is investigated based on methods of spectral analysis to the study of the instantaneous characteristics of signals obtained by means of digital simulation of the dynamic behavior of the power system. The study focuses on the perspectives developed from two different approaches of analysis: the use of lineal methods of spectral analysis and the use of methods of non-lineal analysis, based on the concept of an analytical signal. The developed tools are applied to the study of two phenomena of electromechanical origin of different characteristics in complex power systems. A comparison between the results obtained is performed for these techniques and the possibility of its application is discussed for the problem of on-line identification in power systems. [Spanish] En el presente trabajo de tesis se investiga la aplicacion de tecnicas de identificacion basadas en metodos de analisis espectral al estudio de las caracteristicas instantaneas de senales obtenidas mediante simulacion digital del comportamiento dinamico del sistema de potencia. El estudio se centra en las aproximaciones desarrolladas desde dos enfoques distintos de analisis: la utilizacion de metodos lineales de analisis espectral y la utilizacion de metodos de analisis no lineal, basados en el concepto de una senal analitica. Las herramientas desarrolladas se aplican al estudio de dos fenomenos de origen electromecanico de caracteristicas distintas en sistemas complejos de potencia. Se hace una comparacion entre los resultados obtenidos por estas tecnicas y se discute la posibilidad de su aplicacion al problema de identificacion en linea en sistemas de potencia.

  17. Kineret®/IL-1ra blocks the IL-1/IL-8 inflammatory cascade during recombinant Panton Valentine Leukocidin-triggered pneumonia but not during S. aureus infection.

    Directory of Open Access Journals (Sweden)

    Delphine Labrousse

    Full Text Available OBJECTIVES: Community-acquired Staphylococcus aureus necrotizing pneumonia is a life-threatening disease. Panton Valentine Leukocidin (PVL has been associated with necrotizing pneumonia. PVL triggers inflammasome activation in human macrophages leading to IL-1β release. IL-1β activates lung epithelial cells to release IL-8. This study aimed to assess the relevance of this inflammatory cascade in vivo and to test the potential of an IL-1 receptor antagonist (IL-1Ra/Kineret to decrease inflammation-mediated lung injury. METHODS: We used the sequential instillation of Heat-killed S. aureus and PVL or S. aureus infection to trigger necrotizing pneumonia in rabbits. In these models, we investigated inflammation in the presence or absence of IL-1Ra/Kineret. RESULTS: We demonstrated that the presence of PVL was associated with IL-1β and IL-8 release in the lung. During PVL-mediated sterile pneumonia, Kineret/IL-1Ra reduced IL-8 production indicating the relevance of the PVL/IL-1/IL-8 cascade in vivo and the potential of Kineret/IL-1Ra to reduce lung inflammation. However, Kineret/IL-1Ra was ineffective in blocking IL-8 production during infection with S. aureus. Furthermore, treatment with Kineret increased the bacterial burden in the lung. CONCLUSIONS: Our data demonstrate PVL-dependent inflammasome activation during S.aureus pneumonia, indicate that IL-1 signaling controls bacterial burden in the lung and suggest that therapy aimed at targeting this pathway might be deleterious during pneumonia.

  18. Supervising and leading teams in ILS

    CERN Document Server

    Allan, Barbara

    2013-01-01

    Provides a practical guide to supervisory skills, suitable for team leaders and supervisors in library and information work. Illustrated by examples and case studies from different types of ILS, this book offers self-assessment audits and other activities to enable the reader to relate the tools and techniques to their own work situation.

  19. IL TERREMOTO JONICO DEL 22 APRILE 1948

    Directory of Open Access Journals (Sweden)

    p. Valle

    1951-06-01

    Full Text Available Allo scopo di contribuire alla localizzazione dei centri sismiciche interessano l'Italia e per essere in jtossesso dei dati fondamentaliper una successiva ricerca, sono state calcolate le coordinate epicentralie il tempo origine del terremoto Jonico del 22 aprile 1948.

  20. Il progetto Virgo, Einstein e i computer

    CERN Document Server

    2003-01-01

    "Virgo sta accendendo i suoi laser: mercoledi e stato inaugurato a Pisa il piu potente rivelatore di onde gravitazionali al mondo, capace eventualmente di segnalare l'arrivo di un'onda dal cosmo, con una sensibilita di un miliardesimo di miliardesimo di metro" (1/2 page)

  1. Il significato della relatività

    CERN Document Server

    Einstein, Albert

    1955-01-01

    La prima edizione di questo libro, pubblicata bel 1922, comprendeva il testo delle Stafford Little Lectures tenute da Einstein nel maggio 1921 alla Università di Princeton. Nel 1945 Einstein aggiunse un'appendice sulla sua teoria generalizzata della gravitazione. Nel 1953 Einstein rifece del tutto, ampliandola, la seconda appendice, a cui aggiunse un Supplemento nel 1954.

  2. IL-2 absorption affects IFN-gamma and IL-5, but not IL-4 producing memory T cells in double color cytokine ELISPOT assays.

    Science.gov (United States)

    Quast, Stefan; Zhang, Wenji; Shive, Carey; Kovalovski, Damian; Ott, Patrick A; Herzog, Bernhard A; Boehm, Bernhard O; Tary-Lehmann, Magdalena; Karulin, Alexey Y; Lehmann, Paul V

    2005-09-01

    Cytokine assays are gaining increasing importance for human immune monitoring because they reliably detect antigen-specific T cells in primary PBMC, even at low clonal sizes. Double color ELISPOT assays permit the simultaneous visualization of cells producing two different cytokines. Permitting the simultaneous assessment of type 1 and 2 immunity and due to the limited numbers of PBMC available from human study subjects, double color assays should be particularly attractive for clinical trials. Since the performance of double color assays has not yet been validated, we set out to compare them to single color measurements. Testing the recall antigen-induced cytokine response of PBMC, we found that double color assays regularly provided lower numbers of IFN-gamma and IL-5 spots than single color measurements when IL-2 detection was part of the double color assay. We showed that the inhibitory effect resulted from IL-2 absorption and could be overcome by either antibody free preactivation cultures or by inclusion of anti-CD28 antibody. In contrast, the simultaneous detection of IL-2 did not affect the numbers of IL-4 spots. Therefore, unlike IL-2/IL-4 and IFN-gamma/IL-5 assays, IL-2/IFN-gamma, and IL-2/IL-5 assays require compensation for the IL-2 capture to provide accurate numbers for the frequencies of cytokine producing memory T cells.

  3. Polymorphisms of the IL-6, IL-8 and IL-10 genes and the risk of gastric pathology in patients infected with Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Ivy Bastos Ramis

    2017-04-01

    Conclusion: We demonstrated that polymorphisms in the IL-8 gene was significantly associated with H. pylori infection. Furthermore, polymorphisms in the IL-8 and IL-10 genes were associated with an enhanced risk of peptic ulcer disease in H. pylori-positive patients.

  4. Validation of Hiriart equation to compute steam production by the lip pressure method; Validacion de la ecuacion de Hiriart para calculo de gasto de vapor por el metodo de presion de labio

    Energy Technology Data Exchange (ETDEWEB)

    Flores Armenta, Magaly [Gerencia de Proyectos Geotermoelectricos de la Comision Federal de Electricidad, Morelia (Mexico)

    1996-09-01

    Mainly in new geothermal wells, it is necessary to evaluate the production in a very fast, simple and not expensive way, to know the convenience to install surface equipment, such as silencers and separators, to drive the steam to the commercial gathering system. In practice, one of the most known methods is the lip pressure one, which requires a simple set of installations. The objective of this paper is to validate the steam flow rate calculated by the lip pressure method, with respect to the ASME method. The ASME method is known for its accuracy, and is done by measuring the steam and liquid after a high pressure separator, by an orifice plate of known diameter and a triangular weir. Results of the validation show up the feasibility of application of the lip pressure method by using a simple adjustment equation. Percentage of mistake results less than 1%, without any notable influence of the production enthalpy. That equation to be applied in a general case, is as follows: Q{nu} =(20642)(F*P*D{sup 2}/{radical}h-2000). For the particular case of the Los Azufres geothermal field, the equation is: Q{nu}= 810*P*D{sup 2} [Espanol] En los pozos geotermicos, principalmente en los nuevos, es necesario evaluar su produccion de manera rapida, sencilla y economica, para determinar la conveniencia de instalar equipo superficial, como separadores, silenciadores, etc., que permita la integracion del vapor al sistema comercial de generacion electrica. Para fines practicos uno de los metodos mas conocidos es el de presion de labio, que solo requiere un arreglo sencillo de instalaciones superficiales. En este documento se validan y ajustan los calculos de produccion de vapor por ese metodo de presion de labio, con respecto a las mediciones exactas efectuadas con el metodo ASME. Este ultimo es reconocido internacionalmente por su precision, y se lleva a cabo separando la mezcla obtenida en superficie en un recipiente a presion para medir el vapor a traves de una placa de orificio

  5. GeoCallCenter: quando il GIS entra in simbiosi con il telefono

    Directory of Open Access Journals (Sweden)

    Ivan Tani

    2007-03-01

    illuminazione e delle reti semaforiche. L’idea di un SIT di holding prende corpo nel 2003 con l’obiettivo di costituire un punto di coordinamento nel gestire in maniera omogenea l’informazione geografica e gli applicativi per il trattamento delle medesime, per tutto il gruppo. Il progetto eredita i livelli funzionali e la struttura trasparente del precedente SIT di Seabo S.p.A., in cui aspetti territoriali, ambientali, di gestione, di pianificazione e di servizio al cliente sono stati considerati contestualmente allo sviluppo complessivo del sistema informativo aziendale.

  6. Aberrant plasma IL-7 and soluble IL-7 receptor levels indicate impaired T-cell response to IL-7 in human tuberculosis.

    Directory of Open Access Journals (Sweden)

    Christian Lundtoft

    2017-06-01

    Full Text Available T-cell proliferation and generation of protective memory during chronic infections depend on Interleukin-7 (IL-7 availability and receptivity. Regulation of IL-7 receptor (IL-7R expression and signalling are key for IL-7-modulated T-cell functions. Aberrant expression of soluble (s and membrane-associated (m IL-7R molecules is associated with development of autoimmunity and immune failure in acquired immune deficiency syndrome (AIDS patients. Here we investigated the role of IL-7/IL-7R on T-cell immunity in human tuberculosis. We performed two independent case-control studies comparing tuberculosis patients and healthy contacts. This was combined with follow-up examinations for a subgroup of tuberculosis patients under therapy and recovery. Blood plasma and T cells were characterised for IL-7/sIL-7R and mIL-7R expression, respectively. IL-7-dependent T-cell functions were determined by analysing STAT5 phosphorylation, antigen-specific cytokine release and by analysing markers of T-cell exhaustion and inflammation. Tuberculosis patients had lower soluble IL-7R (p < 0.001 and higher IL-7 (p < 0.001 plasma concentrations as compared to healthy contacts. Both markers were largely independent and aberrant expression normalised during therapy and recovery. Furthermore, tuberculosis patients had lower levels of mIL-7R in T cells caused by post-transcriptional mechanisms. Functional in vitro tests indicated diminished IL-7-induced STAT5 phosphorylation and impaired IL-7-promoted cytokine release of Mycobacterium tuberculosis-specific CD4+ T cells from tuberculosis patients. Finally, we determined T-cell exhaustion markers PD-1 and SOCS3 and detected increased SOCS3 expression during therapy. Only moderate correlation of PD-1 and SOCS3 with IL-7 expression was observed. We conclude that diminished soluble IL-7R and increased IL-7 plasma concentrations, as well as decreased membrane-associated IL-7R expression in T cells, reflect impaired T

  7. Fasting induces IL-1 resistance and free fatty acid-mediated up-regulation of IL-1R2 and IL-1RA

    Directory of Open Access Journals (Sweden)

    jenifer j joesting

    2014-07-01

    Full Text Available Objective: Weight loss is a near societal obsession and many diet programs use significant calorie restriction (CR including fasting/short term starvation to generate rapid effects. Fasting is also a well-recognized cause of immunosuppression especially within the innate immune system. In this study, we sought to determine if the IL-1 arm of the neuroimmune system was down-regulated by a 24 hr fast and how fasting might generate this effect. Design: Mice were allowed ad libitum access to food or had food withheld for 24 hrs. Expression of the endogenous IL-1 antagonists IL-1 receptor type 2 (IL-1R2 and IL-1 receptor antagonist (IL-1RA were determined as were sickness behaviors before and after IL-1 administration.Results: Fasting markedly increased gene expression of IL-1R2 (83-fold in adipose tissue, 9.5-fold in liver and IL-1RA (68-fold in liver. Fasted mice were protected from IL-1-induced weight loss, hypoglycemia, loss of locomotor and social anxiety. These protections were coupled to a large positive interaction of fasting and IL-1 on IL-1R2 gene expression in adipose tissue and liver (2.6-fold and 1.6-fold, respectively. Fasting not only increased IL-1RA and IL-1R2 protein 2.5-fold and 3.2-fold, respectively, in liver; but also increased IL-1R2 1.8-fold in adipose tissue. Fasting, in turn, triggered a 2.4-fold increase in plasma free-fatty acids (FFAs and a 2.1-fold increase in plasma corticosterone. Inhibition, of glucocorticoid action with mifepristone did not impact fasting-dependent IL-1R2 or IL-1RA gene expression. Administration of the FFA, palmitate, to mice increased liver IL-1R2 and IL-1RA gene expression by 14-fold and 11-fold, respectively. Conclusion: These findings indicate that fasting augments expression of endogenous IL-1 antagonists inducing IL-1 resistance. Fasting-induced increases in plasma FFAs appears to be a signal that drives immunosuppression during fasting/short term starvation.

  8. Rappresentare il progetto di interaction Design

    Directory of Open Access Journals (Sweden)

    Michele Zannoni

    2013-03-01

    Full Text Available ItQuesto saggio indaga le conseguenze che, nel mutato contesto del progetto contemporaneo del design, implica la forte convergenza della disciplina del progetto nei temi legati all'interaction design. L'evidenza di questo mutamento mette in luce come nell'iter progettuale il ruolo centrico del disegno e della rappresentazione è messo in crisi da una trasformazione dei contenuti del progetto. Il rapporto tra il progetto dell'interfaccia e il product design, la dematerializzazione dei feedback tattili e visivi, la sempre più diffusa digitalizzazione delle superfici di interazione degli oggetti, mostrano come il design del prodotto non è immune alla trasformazione che ha cambiato i media della comunicazione negli ultimi dieci anni e gli strumenti della rappresentazione si devono adeguare per poter prefigurare una sempre maggior complessità del percorso progettuale.EnIn the changing context of contemporary design, this essay explores the consequences entailed by the significant convergence of the discipline of design towards the themes relative to action design. The evidence of this change highlights how the central role of drawing and representation in the design process is challenged by the transformation in the contents of design. The relationship between the design of the interface and product design, the dematerialization of tactile and visual feedback, the increasingly widespread digitalization of the interaction surfaces of objects, prove that product design is not immune to the transformation that has changed communication media over the past ten years and the tools of representation must adapt to maintain the capacity to prefigure the growing complexity of the design process.

  9. Vaghezza e chiarezza: tradurre Il grande Gatsby

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    Franca Cavagnoli

    2014-05-01

    Full Text Available La traduzione di The Great Gatsby (1925 di Francis Scott Fitzgerald, pubblicata da Feltrinelli nel 2011: dalla tensione fra lingua scritta e lingua orale all’alternarsi di registri linguistici assai vari nei dialoghi (formale, colloquiale, popolare, dalla difficoltà di seguire Fitzgerald nelle sue ellissi all’aderenza sia alle sue scelte stilistiche sia ai campi espressivi da lui prediletti, in particolare l’area semantica del mare, delle tenebre, dell’inquietudine. Nell’articolo entro nel dettaglio delle singole scelte traduttive – attraverso il confronto della traduzione con il testo fonte e la spiegazione delle decisioni prese – compiute all’insegna di una scelta di fondo, e cioè che il fine etico dell’atto traduttivo sia accogliere lo Straniero in quanto tale, affinché nel versare un libro nella propria lingua madre l’Altro resti Altro e il desiderio di tradurre non porti a sostituire il proprio all’altrui. The article retraces the path I followed in my translation, published by Feltrinelli in 2011, of Francis Scott Fitzgerald’s The Great Gatsby (1925 – from the tension between the written and spoken languages to the wide diversity of registers (formal, colloquial, popular in the dialogues, from the difficulty of staying in step with Fitzgerald’s ellipses to the preservation of his stylistic choices and his favourite semantic fields, particularly those of the sea, of darkness and of restlessness. By comparing my translation with the source text and explaining the rationale behind my decisions, I will perform a thorough examination of my translation choices, which have been based on the tenet that the ethical aim of the translation act is to receive the Foreign as Foreign, so that when one turns a book into one’s own mother tongue the Other remains the Other and the wish to translate does not lead one to replace the Other with the Self.  

  10. IL-17 and IL-22 in Cerebrospinal Fluid and Plasma Are Elevated in Guillain-Barré Syndrome

    Directory of Open Access Journals (Sweden)

    Shujuan Li

    2012-01-01

    Full Text Available Guillain-Barré syndrome (GBS is an acute autoimmune-mediated inflammatory demyelinating disease that causes rapidly progressing paralysis and occasionally respiratory failure. We hypothesized that interleukin (IL-17 and IL-22 are elevated in GBS and participate in the autoimmune inflammatory response of GBS. We used sandwich enzyme-linked immunosorbent assay (ELISA to measure the IL-17 and IL-22 levels in the CSF, and plasma from 22 GBS patients at the acute phase and 18 healthy controls (HC. The results show that CSF and plasma levels of IL-17 and IL-22 are elevated in GBS patients compared with HC. IL-17 and IL-22 levels in CSF, respectively, are correlated with GBS disability scale scores (GDSs. Meanwhile, IL-17 and IL-22 levels in CSF, IL-22 in CSF, and plasma of GBS patients have positive correlation, respectively. The increased levels of IL-17 and IL-22 in CSF may be explained by the disruption of blood-brain barrier (BBB and peripheral nervous system (PNS local inflammation in GBS. Meanwhile, the elevated levels of these two cytokines in plasma suggest the activation of Th17 and Th22 cells in the systemic immune response of GBS. Our data provide preliminary evidence that GBS is associated with high levels of IL-17 and IL-22 in CSF and plasma. These cytokines display pathogenic potential and may serve as useful biomarkers for GBS.

  11. IL-4 enhances IL-10 production in Th1 cells: implications for Th1 and Th2 regulation.

    Science.gov (United States)

    Mitchell, Ruth E; Hassan, Masriana; Burton, Bronwen R; Britton, Graham; Hill, Elaine V; Verhagen, Johan; Wraith, David C

    2017-09-12

    IL-10 is an immunomodulatory cytokine with a critical role in limiting inflammation in immune-mediated pathologies. The mechanisms leading to IL-10 expression by CD4 + T cells are being elucidated, with several cytokines implicated. We explored the effect of IL-4 on the natural phenomenon of IL-10 production by a chronically stimulated antigen-specific population of differentiated Th1 cells. In vitro, IL-4 blockade inhibited while addition of exogenous IL-4 to Th1 cultures enhanced IL-10 production. In the in vivo setting of peptide immunotherapy leading to a chronically stimulated Th1 phenotype, lack of IL-4Rα inhibited the induction of IL-10. Exploring the interplay of Th1 and Th2 cells through co-culture, Th2-derived IL-4 promoted IL-10 expression by Th1 cultures, reducing their pathogenicity in vivo. Co-culture led to upregulated c-Maf expression with no decrease in the proportion of T-bet + cells in these cultures. Addition of IL-4 also reduced the encephalitogenic capacity of Th1 cultures. These data demonstrate that IL-4 contributes to IL-10 production and that Th2 cells modulate Th1 cultures towards a self-regulatory phenotype, contributing to the cross-regulation of Th1 and Th2 cells. These findings are important in the context of Th1 driven diseases since they reveal how the Th1 phenotype and function can be modulated by IL-4.

  12. The role of IL-33 in rheumatic diseases.

    Science.gov (United States)

    Duan, Lihua; Chen, Jie; Gong, Feili; Shi, Guixiu

    2013-01-01

    Interleukin-33 (IL-33), a novel member of IL-1 family, has been recently implicated in several inflammatory and autoimmune diseases. IL-33 can be produced by various types of tissues and cells and induce gene expression of Th2-associated cytokines via binding to the orphan receptor ST2. By promoting Th2 type immune response, IL-33 plays important roles in the allergy, whereas its function in autoimmune diseases attracts more attention. Recent studies reported the correlation of IL-33 with rheumatic diseases, and most of them found that the IL-33 expression levels were consistent with disease activity and development. Furthermore, evidence has indicated that IL-33-related treatment may ameliorate the pathogenic conditions and attenuate disease progression of those rheumatic diseases. Therefore, elucidation of the roles of IL-33 in rheumatic diseases would be beneficial to understand the pathogenesis and therapy of these diseases. In this paper, we will summarize the roles of IL-33 in the rheumatic diseases.

  13. Factors Associated With Plasma IL-6 Levels During HIV Infection

    DEFF Research Database (Denmark)

    Borges, Álvaro H; O'Connor, Jemma L; Phillips, Andrew N

    2015-01-01

    BACKGROUND: Elevated interleukin 6 (IL-6) levels have been linked to cardiovascular disease, cancer and death. Persons with human immunodeficiency virus (HIV) infection receiving treatment have higher IL-6 levels, but few data are available on factors associated with circulating IL-6. METHODS......: Participants in 3 trials with IL-6 measured at baseline were included (N = 9864). Factors associated with IL-6 were identified by linear regression. Demographic and HIV variables (nadir/entry CD4(+) cell count, HIV RNA level, antiretroviral therapy regimen) were investigated in all 3 trials. In the SMART...... education, whereas black race was associated with lower IL-6. Higher HIV RNA levels were associated with higher IL-6 levels, and higher nadir CD4(+) cell counts with lower IL-6 levels. Compared with efavirenz, protease inhibitors were associated with higher and nevirapine with lower IL-6 levels. Smoking...

  14. Effects of cranberry components on IL-1β-stimulated production of IL-6, IL-8 and VEGF by human TMJ synovial fibroblasts.

    Science.gov (United States)

    Tipton, David A; Christian, James; Blumer, Adam

    2016-08-01

    Osteoarthritis (OA) in the TMJ is characterized by deterioration of articular cartilage and secondary inflammatory changes. Interleukin-1β (IL-1β) stimulates IL-6, IL-8, and vascular endothelial growth factor (VEGF) in synovial fluid of TMJ with internal derangement and bony changes. The cranberry (Vaccinium macrocarpon) contains polyphenolic compounds that inhibit production of pro-inflammatory molecules by gingival cells in response to several stimulators. This study examined effects of cranberry components on IL-1β-stimulated IL-6, IL-8, and VEGF production by human TMJ synovial fibroblast-like cells. Cranberry high molecular weight non-dialyzable material (NDM) was derived from cranberry juice. Human TMJ synovial fibroblast-like cells from joints with degenerative OA and an ankylosed TMJ without degeneration were incubated with IL-1β (0.001-1nM)±NDM (25-250μg/ml) (2h preincubation). Viability was assessed via activity of a mitochondrial enzyme. IL-6, IL-8, and VEGF in culture supernatants were measured by ELISA; NF-κB and AP-1 transcription factors were measured in nuclear extracts via binding to specific oligonucleotides. ANOVA and Scheffe's F procedure for post hoc comparisons. NDM did not affect cell viability but inhibited IL-1β stimulated IL-6, IL-8, and VEGF production in all cell lines (pCranberry NDM inhibition of IL-1β-stimulated IL- 6, IL-8, and VEGF production by TMJ synovial fibroblast-like cells suggests that cranberry components may be useful as a host modulatory therapeutic agent to prevent or treat inflammatory arthropathies of the TMJ. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Interleukin-23 (IL-23), independent of IL-17 and IL-22, drives neutrophil recruitment and innate inflammation during Clostridium difficile colitis in mice.

    Science.gov (United States)

    McDermott, Andrew J; Falkowski, Nicole R; McDonald, Roderick A; Pandit, Chinmay R; Young, Vincent B; Huffnagle, Gary B

    2016-01-01

    Our objective was to determine the role of the inflammatory cytokine interleukin-23 (IL-23) in promoting neutrophil recruitment, inflammatory cytokine expression and intestinal histopathology in response to Clostridium difficile infection. Wild-type (WT) and p19(-/-) (IL-23KO) mice were pre-treated with cefoperazone in their drinking water for 5 days, and after a 2-day recovery period were challenged with spores from C. difficile strain VPI 10463. Interleukin-23 deficiency was associated with significant defects in both the recruitment of CD11b(High) Ly6G(H) (igh) neutrophils to the colon and the expression of neutrophil chemoattractants and stabilization factors including Cxcl1, Cxcl2, Ccl3 and Csf3 within the colonic mucosa as compared with WT animals. Furthermore, the expression of inflammatory cytokines including Il33, Tnf and Il6 was significantly reduced in IL-23-deficient animals. There was also a trend towards less severe colonic histopathology in the absence of IL-23. The induction of Il17a and Il22 was also significantly abrogated in IL-23KO mice. Inflammatory cytokine expression and neutrophilic inflammation were not reduced in IL-17a-deficient mice or in mice treated with anti-IL-22 depleting monoclonal antibody. However, induction of RegIIIg was significantly reduced in animals treated with anti-IL-22 antibody. Taken together, these data indicate that IL-23, but not IL-17a or IL-22, promotes neutrophil recruitment and inflammatory cytokine and chemokine expression in the colon in response to C. difficile infection. © 2015 John Wiley & Sons Ltd.

  16. 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

  17. Curcumin blocks interleukin (IL)-2 signaling in T-lymphocytes by inhibiting IL-2 synthesis, CD25 expression, and IL-2 receptor signaling

    International Nuclear Information System (INIS)

    Forward, Nicholas A.; Conrad, David M.; Power Coombs, Melanie R.; Doucette, Carolyn D.; Furlong, Suzanne J.; Lin, Tong-Jun; Hoskin, David W.

    2011-01-01

    Highlights: → Curcumin inhibits CD4 + T-lymphocyte proliferation. → Curcumin inhibits interleukin-2 (IL-2) synthesis and CD25 expression by CD4 + T-lymphocytes. → Curcumin interferes with IL-2 receptor signaling by inhibiting JAK3 and STAT5 phosphorylation. → IL-2-dependent regulatory T-lymphocyte function and Foxp3 expression is downregulated by curcumin. -- Abstract: Curcumin (diferulomethane) is the principal curcuminoid in the spice tumeric and a potent inhibitor of activation-induced T-lymphocyte proliferation; however, the molecular basis of this immunosuppressive effect has not been well studied. Here we show that micromolar concentrations of curcumin inhibited DNA synthesis by mouse CD4 + T-lymphocytes, as well as interleukin-2 (IL-2) and CD25 (α chain of the high affinity IL-2 receptor) expression in response to antibody-mediated cross-linking of CD3 and CD28. Curcumin acted downstream of protein kinase C activation and intracellular Ca 2+ release to inhibit IκB phosphorylation, which is required for nuclear translocation of the transcription factor NFκB. In addition, IL-2-dependent DNA synthesis by mouse CTLL-2 cells, but not constitutive CD25 expression, was impaired in the presence of curcumin, which demonstrated an inhibitory effect on IL-2 receptor (IL-2R) signaling. IL-2-induced phosphorylation of STAT5A and JAK3, but not JAK1, was diminished in the presence of curcumin, indicating inhibition of critical proximal events in IL-2R signaling. In line with the inhibitory action of curcumin on IL-2R signaling, pretreatment of CD4 + CD25 + regulatory T-cells with curcumin downregulated suppressor function, as well as forkhead box p3 (Foxp3) expression. We conclude that curcumin inhibits IL-2 signaling by reducing available IL-2 and high affinity IL-2R, as well as interfering with IL-2R signaling.

  18. Curcumin blocks interleukin (IL)-2 signaling in T-lymphocytes by inhibiting IL-2 synthesis, CD25 expression, and IL-2 receptor signaling

    Energy Technology Data Exchange (ETDEWEB)

    Forward, Nicholas A.; Conrad, David M. [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Power Coombs, Melanie R.; Doucette, Carolyn D. [Department of Pathology, Dalhousie University, Halifax, Nova Scotia (Canada); Furlong, Suzanne J. [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Lin, Tong-Jun [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia (Canada); Hoskin, David W., E-mail: d.w.hoskin@dal.ca [Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia (Canada); Department of Pathology, Dalhousie University, Halifax, Nova Scotia (Canada); Department of Surgery, Dalhousie University, Halifax, Nova Scotia (Canada)

    2011-04-22

    Highlights: {yields} Curcumin inhibits CD4{sup +} T-lymphocyte proliferation. {yields} Curcumin inhibits interleukin-2 (IL-2) synthesis and CD25 expression by CD4{sup +} T-lymphocytes. {yields} Curcumin interferes with IL-2 receptor signaling by inhibiting JAK3 and STAT5 phosphorylation. {yields} IL-2-dependent regulatory T-lymphocyte function and Foxp3 expression is downregulated by curcumin. -- Abstract: Curcumin (diferulomethane) is the principal curcuminoid in the spice tumeric and a potent inhibitor of activation-induced T-lymphocyte proliferation; however, the molecular basis of this immunosuppressive effect has not been well studied. Here we show that micromolar concentrations of curcumin inhibited DNA synthesis by mouse CD4{sup +} T-lymphocytes, as well as interleukin-2 (IL-2) and CD25 ({alpha} chain of the high affinity IL-2 receptor) expression in response to antibody-mediated cross-linking of CD3 and CD28. Curcumin acted downstream of protein kinase C activation and intracellular Ca{sup 2+} release to inhibit I{kappa}B phosphorylation, which is required for nuclear translocation of the transcription factor NF{kappa}B. In addition, IL-2-dependent DNA synthesis by mouse CTLL-2 cells, but not constitutive CD25 expression, was impaired in the presence of curcumin, which demonstrated an inhibitory effect on IL-2 receptor (IL-2R) signaling. IL-2-induced phosphorylation of STAT5A and JAK3, but not JAK1, was diminished in the presence of curcumin, indicating inhibition of critical proximal events in IL-2R signaling. In line with the inhibitory action of curcumin on IL-2R signaling, pretreatment of CD4{sup +}CD25{sup +} regulatory T-cells with curcumin downregulated suppressor function, as well as forkhead box p3 (Foxp3) expression. We conclude that curcumin inhibits IL-2 signaling by reducing available IL-2 and high affinity IL-2R, as well as interfering with IL-2R signaling.

  19. The interleukin (IL)-23/IL-17 axis in ankylosing spondylitis: new advances and potentials for treatment.

    Science.gov (United States)

    Jethwa, H; Bowness, P

    2016-01-01

    Ankylosing spondylitis (AS), the most common form of spondyloarthropathy, is a chronic, progressive multi-system inflammatory disorder characteristically affecting the sacroiliac joints and axial skeleton. Although the exact mechanisms underlying the pathogenesis of AS remain to be elucidated, the presence of human leucocyte antigen (HLA)-B27 is known to markedly increase its risk of development. Current treatments include non-steroidal anti-inflammatory drugs (NSAIDs) and tumour necrosis factor (TNF) blockers. In recent years, the interleukin (IL)-23/IL-17 pathway has been shown to have significance in the pathogenesis of AS and treatment modalities targeting this pathway have been shown to be beneficial in various other inflammatory conditions. This review provides an overview of the IL-23/IL-17 pathway in the pathogenesis of AS and summarizes new potential treatments for AS and related inflammatory diseases. © 2015 British Society for Immunology.

  20. Serum concentration of IL-6, IL-2, TNF-α, and IFNγ in Vitiligo patients

    Directory of Open Access Journals (Sweden)

    Suman Singh

    2012-01-01

    Full Text Available Background: Vitiligo is an acquired depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. Although the etiology of vitiligo is unknown, over the last few years, substantial data from clinical research has greatly supported the ′Autoimmune theory′ and this is supported by the frequent association of vitiligo with disorders that have an autoimmune origin, including Hashimoto′s thyroiditis, Graves disease, type 1 insulin-dependent diabetes mellitus, and Addison′s disease. As cytokines are important mediators of immunity, there is evidence to suggest that they play a major role in the pathogenesis of autoimmune diseases. Aim: Keeping this in view we have assayed sera for cytokine IL-6, IL-2, Tumor necrosis factor (TNF-α, and IFNγ in 80 cases of vitiligo and compared it with healthy subjects, in order to find out whether they play a role in the pathogenesis of vitiligo or not. Materials and Methods: Serum IL-6, IL-2, TNF-α, and IFNγ were done by the indirect enzyme linked immunosorbent assay (ELISA. Results: The mean serum IL-6 and IL-2 levels in the patient group were significantly higher when compared with those of the normal controls. The mean serum IFNγ level in patients with vitiligo was significantly lower than that in the control group. There was no significant difference in the serum level of TNF-α between vitiligo and healthy controls. Conclusion : An increase in the production of proinflammatory cytokines such as IL-6 and IL-2 in vitiligo patients may play an important role in melanocytic cytotoxicity. Thus, we speculate that the cytokine production of epidermal microenvironment may be involved in vitiligo.

  1. IL-2, IL-7 and IL-15 as immuno-modulators during SIV/HIV vaccination and treatment.

    Science.gov (United States)

    Leone, Amanda; Picker, Louis J; Sodora, Donald L

    2009-01-01

    While highly active antiretroviral therapy (HAART) regimens have proven to be effective in controlling active HIV replication, complete recovery of CD4+ T cells does not always occur, even among patients with high level virologic control. Recent advances in understanding the biology of T cell production and homeostasis have created the potential to augment anti-viral therapies with immunotherapies designed to facilitate recovery of the HIV-damaged immune system, in particular, the recovery of CD4+ T cell populations. The common gamma-chain cytokines IL-2, IL-7 and IL-15 are primary regulators of T cell homeostasis and thus have been considered prime candidate immunotherapeutics, both for increasing T cell levels/function and for augmenting vaccine-elicited viral-specific T cell responses. Recent studies have established that these cytokines have distinct functional roles in immune homeostasis, which focus on specific T cell populations. The ability of these cytokines to provide immunotherapeutic benefit to HIV+ patients will depend on their ability to stably increase or functionally enhance the desired T cell target population without adverse virologic or clinical consequences.

  2. An analysis of IL-36 signature genes and individuals with IL1RL2 knockout mutations validates IL-36 as a psoriasis therapeutic target.

    Science.gov (United States)

    Mahil, Satveer K; Catapano, Marika; Di Meglio, Paola; Dand, Nick; Ahlfors, Helena; Carr, Ian M; Smith, Catherine H; Trembath, Richard C; Peakman, Mark; Wright, John; Ciccarelli, Francesca D; Barker, Jonathan N; Capon, Francesca

    2017-10-11

    Interleukin (IL)-36α, IL-36β, and IL-36γ are innate mediators of acute epithelial inflammation. We sought to demonstrate that these cytokines are also required for the pathogenesis of plaque psoriasis, a common and chronic skin disorder, caused by abnormal T helper 17 (T H 17) cell activation. To investigate this possibility, we first defined the genes that are induced by IL-36 cytokines in primary human keratinocytes. This enabled us to demonstrate a significant IL-36 signature among the transcripts that are up-regulated in plaque psoriasis and the susceptibility loci associated with the disease in genome-wide studies. Next, we investigated the impact of in vivo and ex vivo IL-36 receptor blockade using a neutralizing antibody or a recombinant antagonist. Both inhibitors had marked anti-inflammatory effects on psoriatic skin, demonstrated by statistically significant reductions in IL-17 expression, keratinocyte activation, and leukocyte infiltration. Finally, we explored the potential safety profile associated with IL-36 blockade by phenotyping 12 individuals carrying knockout mutations of the IL-36 receptor gene. We found that normal immune function was broadly preserved in these individuals, suggesting that IL-36 signaling inhibition would not substantially compromise host defenses. These observations, which integrate the results of transcriptomics and model system analysis, pave the way for early-stage clinical trials of IL-36 antagonists. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  3. The effects of IL-10 gene polymorphism on serum, and gingival crevicular fluid levels of IL-6 and IL-10 in chronic periodontitis.

    Science.gov (United States)

    Toker, Hulya; Gorgun, Emine Pirim; Korkmaz, Ertan Mahir; Yüce, Hatice Balci; Poyraz, Omer

    2018-01-01

    Anti-inflammatory cytokines play a crucial role in periodontitis by inhibiting synthesis of pro-inflammatory cytokines. The purpose of this study was to evaluate the effect of interleukin-10 (-597) gene polymorphism and genotype distributions on chronic periodontitis (CP) development and IL-6 and IL-10 levels in gingival crevicular fluid (GCF) and serum before and after non-surgical periodontal treatment. The study population consisted of 55 severe generalized CP patients as CP group and 50 healthy individuals as control group. Plaque index, gingival index, probing depth and clinical attachment level were recorded and GCF and blood samples were taken at both the baseline and the sixth week after non-surgical periodontal treatment. PCR-RFLP procedure was used for gene analyses and cytokine levels were measured via ELISA. IL-10 genotype distribution was significantly different between CP and control groups (p=0.000, OR:7, 95%CI, 2.83-60.25). Clinical measurements significantly improved in the CP group after periodontal treatment (p0.05). Sixth week GCF IL-10 levels were significantly lower in patients carrying IL-10 AC+CC genotype compared to the patients carrying IL-10 AA genotype (p0.05). IL-10 AA genotype carriers had lower IL-6 and IL-6/10 levels in serum; however, GCF IL-6/10 levels were similar in both genotypes. Within the limitations of our study, a possible association between IL-10(-597) gene polymorphism and CP might be considered.

  4. Preparation and validation of radio iodinated recombinant human IL-10 for the measurement of natural human antibodies against IL-10

    DEFF Research Database (Denmark)

    de Lemos Rieper, Carina; Galle, Pia; Svenson, Morten

    2009-01-01

    Radio iodinated recombinant human IL-10 was prepared and validated for the measurement of natural human anti-IL-10 antibodies. Iodination of IL-10 was accomplished by means of the chloramine-T method. The crude tracer was purified by size chromatography as homo-dimeric IL-10 with a specific...... activity of 75 cpm/pg. Validation of the tracer confirmed preserved antibody epitopes and receptor binding ability. A robust Radio Immuno Assay (RIA) was developed and validated to detect natural human anti-IL-10 antibodies based on the formation of (125)I-labeled IL-10-IgG complexes in solution...... and separation of the complexes by chromatography on mini-columns. The RIA was applied to 3360 plasma samples derived from normal Danish blood donors. Generally, IL-10 did not bind to plasma factors other than natural anti-IL-10 IgG antibodies. The prevalence of donors high positive for antibodies against IL-10...

  5. The early IL-6 and IL-10 response in trauma is correlated with injury severity and mortality

    DEFF Research Database (Denmark)

    Stensballe, J; Christiansen, M; Tønnesen, E

    2009-01-01

    BACKGROUND: Trauma has previously been shown to influence interleukin (IL)-6 and IL-10 levels, but the association of injury severity and mortality with IL-6 and IL-10 responses in the early phase of accidental trauma remains to be investigated. We wished to describe serum levels of IL-6 and IL-10...... period. Serum levels of IL-6 and IL-10 were measured upon arrival and at 6, 12, and 24 h after admittance using an enzyme-linked immunosorbent assay. Correlation analysis was used to assess the relationship between Injury Severity Score (ISS) and levels of IL-6 and IL-10. Analysis of variance was used...... to describe the IL-6 and IL-10 concentrations in relation to 30-day mortality in a mixed-effect model repeated measures analysis. RESULTS: Mortality was 10.9% (29/265) at 30 days. A significant increase of both IL-6 and IL-10 concentrations was found over time, and a significant correlation was found between...

  6. IL-4 Modulates CCL11 and CCL20 Productions from IL-1β-Stimulated Human Periodontal Ligament Cells

    Directory of Open Access Journals (Sweden)

    Yoshitaka Hosokawa

    2016-01-01

    Full Text Available Background/Aims: IL-4 is a multifunctional cytokine that is related with the pathological conditions of periodontal disease. However, it is uncertain whether IL-4 could control T cells migration in periodontal lesions. The aim of this study was to examine the effects of IL-4 on CCL11, which is a Th2-type chemokine, and CCL20, which is related with Th17 cells migration, productions from human periodontal ligament cells (HPDLCs. Methods: CCL20 and CCL11 productions from HPDLCs were monitored by ELISA. Western blot analysis was performed to detect phosphorylations of signal transduction molecules in HPDLCs. Results: IL-1β could induce both CCL11 and CCL20 productions in HPDLCs. IL-4 enhanced CCL11 productions from IL-1β-stimulated HPDLCs, though IL-4 inhibited CCL20 production. Western blot analysis showed that protein kinase B (Akt and signal transducer and activator of transcription (STAT6 pathways were highly activated in IL-4/IL-1β-stimulated HPDLCs. Akt and STAT6 inhibitors decreased CCL11 production, but enhanced CCL20 production in HPDLCs stimulated with IL-4 and IL-1β. Conclusions: These results mean that IL-4 enhanced Th2 cells migration in periodontal lesion to induce CCL11 production from HPDLCs. On the other hand, IL-4 inhibits Th17 cells accumulation in periodontally diseased tissues to inhibit CCL20 production. Therefore, IL-4 is positively related with the pathogenesis of periodontal disease to control chemokine productions in periodontal lesions.

  7. Hepatitis B virus induces IL-23 production in antigen presenting cells and causes liver damage via the IL-23/IL-17 axis.

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    Qinghong Wang

    Full Text Available IL-23 regulates myriad processes in the innate and adaptive immune systems, and is a critical mediator of the proinflammatory effects exerted by Th17 cells in many diseases. In this study, we investigated whether and how hepatitis B virus (HBV causes liver damage directly through the IL-23 signaling pathway. In biopsied liver tissues from HBV-infected patients, expression of both IL-23 and IL-23R was remarkably elevated. In vivo observations also indicated that the main sources of IL-23 were myeloid dendritic cells (mDCs and macrophages. Analysis of in vitro differentiated immature DCs and macrophages isolated from healthy donors revealed that the HBV surface antigen (HBsAg efficiently induces IL-23 secretion in a mannose receptor (MR-dependent manner. Culture with an endosomal acidification inhibitor and the dynamin inhibitor showed that, upon binding to the MR, the HBsAg is taken up by mDCs and macrophages through an endocytosis mechanism. In contrast, although the HBV core antigen (HBcAg can also stimulate IL-23 secretion from mDCs, the process was MR- and endocytosis-independent. In addition, IL-23 was shown to be indispensible for HBsAg-stimulated differentiation of naïve CD4(+ T cells into Th17 cells, which were determined to be the primary source of IL-17 in HBV-infected livers. The cognate receptor, IL-17R, was found to exist on the hepatic stellate cells and mDCs, both of which might represent the potential target cells of IL-17 in hepatitis B disease. These data provide novel insights into a yet unrecognized mechanism of HBV-induced hepatitis, by which increases in IL-23 expression, through an MR/endocytosis-dependent or -independent manner, produce liver damage through the IL-23/IL-17 axis.

  8. IL-11 and IL-11Rα immunolocalisation at primate implantation sites supports a role for IL-11 in placentation and fetal development

    Directory of Open Access Journals (Sweden)

    Stoikos C

    2003-04-01

    Full Text Available Abstract Embryo implantation, endometrial stromal cell decidualization and formation of a functional placenta are critical processes in the establishment and maintenance of pregnancy. Interleukin (IL-11 signalling is essential for adequate decidualization in the mouse uterus and IL-11 promotes decidualization in the human. IL-11 action is mediated via binding to the specific IL-11 receptor α (IL-11Rα. The present study examined immunoreactive IL-11 and IL-11Rα in cycling rhesus monkey endometrium, at implantation sites in cynomolgus and rhesus monkeys and in human first trimester decidua and defined distinct spatial and temporal patterns. In cycling rhesus monkey endometrium, IL-11 and IL-11Rα increased in both basalis and functionalis regions during the secretory compared with the proliferative phase, with changing cellular locations in luminal and glandular epithelium and stroma. The patterns were similar overall to those previously described in human endometrium. Differences were seen in immunostaining during implantation in cynomologus and rhesus monkey. In the cynomolgus, very little staining for IL-11 or IL-11Rα was seen in syncytio- and cyto-trophoblast cells in the villi between days 12 and 150 of pregnancy although there was moderate staining in cytotrophoblast in the shell between days 12 and 17 and in subpopulations of cytotrophoblast cells invading the arteries at day 17. By contrast in the rhesus monkey between days 24 and 35 of pregnancy and in human first trimester placenta, cyto- and syncytio-trophoblast in the villi but not cytotrophoblast in the shell were positively stained. The most intense staining for both IL-11 and IL-11Rα was present within the decidua in the maternal component of implantation sites in all three primates but moderate staining was also present in maternal vascular smooth muscle and glands perivascular cells and epithelial plaques. These results are consistent with a role for IL-11 both during

  9. IL-36α Regulates Tubulointerstitial Inflammation in the Mouse Kidney

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    Osamu Ichii

    2017-10-01

    Full Text Available IL-36α, a member of the IL-1 family, is a crucial mediator of inflammatory responses. We previously found that IL-36α was overexpressed in injured distal tubules (DTs; however, its pathological function remains unclear. Herein, unilateral ureter obstruction (UUO or folic acid (FA injection was performed in mouse kidneys to assess the role of IL-36α in kidney injury. IL-36α mRNA and protein expression significantly increased in the kidneys within 24 h after UUO. IL-36α localized to dilated DTs. IL-36α expression significantly correlated with the progression of tubulointerstitial cell infiltration and tubular epithelium cell death in UUO kidneys and with renal dysfunction in FA-induced acute kidney injury mice. At 24 h after UUO, IL-36α+ DT epithelial cells showed loose intercellular digitations. IL-1RL2, an IL-36α receptor protein, localized to podocytes, proximal tubules, and DTs in the healthy kidney. IL-1RL2 was expressed in interstitial cells and platelets or extended primary cilia of DT epithelial cells in UUO kidneys. IL-36α stimulation promoted the production of IL-6 and Prss35, an inflammatory cytokine and collagen remodeling-associated enzyme, respectively, in cultured NIH3T3 fibroblasts. UUO-treated IL-36α-knockout (KO mice showed milder kidney injury features than wild-type (WT mice did. In UUO kidneys from IL-36α-KO mice, the expression of genes associated with inflammatory response and sensory perception was significantly different from that in WT mice. Altogether, our data indicate an association between intrarenal IL-36α overexpression and the progression of tubulointerstitial inflammations and morpho-functional alterations of DT epithelial cells. IL-36α may be a novel kidney injury marker useful for evaluating DT damages.

  10. Active immunization against IL-23p19 improves experimental arthritis.

    Science.gov (United States)

    Ratsimandresy, Rojo Anthony; Duvallet, Emilie; Assier, Eric; Semerano, Luca; Delavallée, Laure; Bessis, Natacha; Zagury, Jean-François; Boissier, Marie-Christophe

    2011-11-21

    IL-23 is a pro-inflammatory cytokine essential for the differentiation of Th17 lymphocytes, a subtype of T lymphocyte implied in auto-immunity. IL-23 shares a subunit with IL-12, IL-12/23p40, and comprises a specific subunit, IL-23p19. We previously demonstrated that active immunization against entire TNF-α and against peptides of IL-1β was protective in animal models of rheumatoid arthritis. The aim of this study was to evaluate the effect of peptide-based vaccines targeting the IL-23p19 subunit in collagen-induced arthritis (CIA). Using bioinformatics, the murine IL-23p19 subunit was modeled and two peptides were defined in the receptor interacting domain. Each peptide was coupled to keyhole limpet hemocyanin (KLH) to obtain two vaccines IL23-K1 and IL23-K2. Both vaccines were used for immunizations in incomplete Freund adjuvant (IFA) in groups of DBA/1 mice. Control groups received KLH or PBS at the same dates. CIA was induced by two subcutaneous injections of bovine type II collagen (CIIb), and the development of disease assessed during the next two months. Anti-CIIb and anti-IL-23 antibody levels were assessed by ELISA. Pro- and anti-inflammatory cytokines mRNA were quantified by qRT-PCR in the spleen and the synovium. T-cell populations in the spleen were evaluated by FACS analysis. The clinical scores showed that mice treated with IL23-K1 developed less arthritis than negative controls (panti-IL-23 antibodies than those immunized with IL23-K2 (peffect on IL-17 level. Histological examination showed that IL23-K1 strongly protected against joint destruction and inflammation (pvaccination strategy is protective in CIA. This specific targeting of IL-23 might constitute a promising therapeutic approach to explore in rheumatoid arthritis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. DMPD: Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15546391 Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4. Watf...ord WT, Hissong BD, Bream JH, Kanno Y, Muul L, O'Shea JJ. Immunol Rev. 2004 Dec;202:139-56. (.png) (.svg) (....html) (.csml) Show Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4. PubmedID 15546391 T...itle Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4. Author...s Watford WT, Hissong BD, Bream JH, Kanno Y, Muul L, O'Shea JJ. Publication Immunol Rev. 2004 Dec;202:139-56

  12. Study on the changes of serum IL-2, IL-6 and TNF-α levels in patients with psoriasis

    International Nuclear Information System (INIS)

    Xie Chuntao

    2007-01-01

    Objective: To investigate the changes of serum IL-2, IL-6 and TNF-α levels in patients with psoriasis. Methods: Serum IL-2, IL-6 and TNF-α levels were measured with KIA in 38 patients with psoriasis and 35 controls. Results: Serum levels of IL-6 and TNF-α were significantly higher in patients with psoriasis than those in controls (P<0.01), but serum IL-2 levels were significantly lower (P<0.01). Conclusion: These cytokines participated in the pathogenesis of psoriasis. Monitoring the changes of their serum levels was helpful for the management of the diseases. (authors)

  13. Il museo della scienza di Villa Farnesina

    Directory of Open Access Journals (Sweden)

    Francesca Salvemini

    2005-02-01

    Full Text Available Rappresentavano l’Astronomia le due logge romane del viridario di villa Farnesina con la Sala adiacente del Trionfo di Ercole: lo spazio, l’astrolabio zodiacale della Sala di Galatea - in testa le stelle dell’Orsa minore fatte di “sasso” da Medusa, Peruzzi nella biografia di Vasari - e il tempo, la meccanica dello gnomone solare del Trionfo di Cupido.

  14. I processorie Itanium "accelerano" il CERN

    CERN Multimedia

    2001-01-01

    "Il CERN è di nuovo in prima fila nell'abbinamento tra informatica e ricerca scientifica. L'organizzazione europea utilizzerà anche computer basati sui nuovi microprocessori Intel Itanium a 64 bit". - CERN is again at the forefront of the coupling of informatics and scientific research. The European organization will use computers with new 64 bit Intel Itanium microprocessors (0.5 page)

  15. IL-6, TNF-α, IL-10, and nutritional status in pediatric patients with biliary atresia,

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    Maria Ines de Albuquerque Wilasco

    Full Text Available Abstract Objectives: The objective of the present study is to evaluate whether IL-6, TNF-α, IL-10 are associated with nutritional status in patients with cirrhosis secondary to biliary atresia and compare to healthy controls. Methods: The parameters used for nutritional assessment were the standard deviation scores of height-for-age and of triceps skinfold thickness-for-age. The severity of cirrhosis was evaluated using the Child–Pugh score and PELD/MELD. Serum cytokines were measured using Cytometric Bead Array flow cytometry. Results: IL-6, TNF-α, and IL-10 were significantly higher in the cirrhosis group when compared with the control group (2.4 vs. 0.24 (p < 0.001, 0.21 vs. 0.14 (p = 0.007, and 0.65 vs. 0.36 (p = 0.004, respectively. IL-6 and IL-10 were positively correlated with disease severity (0.450 [p = 0.001] and 0.410; [p = 0.002], respectively. TNF-α did not show a significant correlation with disease severity (0.100; p = 0.478. Regarding nutritional evaluation, IL-6 was negatively correlated with the standard deviation score of height-for-age (−0.493; p < 0.001 and of triceps skinfold thickness-for-age (−0.503; p < 0.001, respectively. IL-10 exhibited a negative correlation with the standard deviation score of height-for-age (−0.476; p < 0.001 and the standard deviation score of triceps skinfold thickness-for-age (−0.388; p = 0.004. TNF-α did not show any significance in both anthropometric parameters (−0.083 (p = 0.555 and −0.161 (p = 0.253. Conclusion: The authors suggest that, in patients with cirrhosis secondary to biliary atresia, IL-6 could be used as a possible supporting biomarker of deficient nutritional status and elevated IL-10 levels could be used as a possible early-stage supporting biomarker of deteriorating nutritional status.

  16. Increased IL-10 mRNA and IL-23 mRNA expression in multiple sclerosis: interferon-beta treatment increases IL-10 mRNA expression while reducing IL-23 mRNA expression

    DEFF Research Database (Denmark)

    Krakauer, M.; Sorensen, P.; Khademi, M.

    2008-01-01

    volunteers served to confirm initial findings. mRNA was analyzed by real-time reverse transcriptase polymerase chain reaction (PCR). RESULTS: We found elevated expression of interleukin (IL)-23 and IL-10 in untreated MS patients. IFN-beta therapy increased IL-10 and decreased IL-23 expression independently...... of the regulatory cytokine IL-10. The elevated IL-23 mRNA levels in MS patients are noteworthy in view of the newly discovered IL-23-driven Th17 T-cell subset, which is crucial in animal models of MS. Since IFN-beta therapy resulted in decreased IL-23 mRNA levels, the Th17 axis could be another target of IFN...

  17. The effect of IL-13 and IL-13R130Q, a naturally occurring IL-13 polymorphism, on the gene expression of human airway smooth muscle cells

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    Amegadzie Bernard

    2005-01-01

    Full Text Available Abstract Background Growing evidence shows that interleukin 13 (IL-13 may play an essential role in the development of airway inflammation and bronchial hyper-responsiveness (BHR, two defining features of asthma. Although the underlying mechanisms remain unknown, a number of reports have shown that IL-13 may exert its deleterious effects in asthma by directly acting on airway resident cells, including epithelial cells and airway smooth muscle cells. In this report, we hypothesize that IL-13 may participate in the pathogenesis of asthma by activating a set of "pro-asthmatic" genes in airway smooth muscle (ASM cells. Methods Microarray technology was used to study the modulation of gene expression of airway smooth muscle by IL-13 and IL-13R130Q. TaqMan™ Real Time PCR and flow cytometry was used to validate the gene array data. Results IL-13 and the IL-13 polymorphism IL-13R130Q (Arg130Gln, recently associated with allergic asthma, seem to modulate the same set of genes, which encode many potentially interesting proteins including vascular cellular adhesion molecule (VCAM-1, IL-13Rα2, Tenascin C and Histamine Receptor H1, that may be relevant for the pathogenesis of asthma. Conclusions The data supports the hypothesis that gene modulation by IL-13 in ASM may be essential for the events leading to the development of allergic asthma.

  18. IL-4 deficiency is associated with mechanical hypersensitivity in mice.

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    Nurcan Üçeyler

    Full Text Available Interleukin-4 (IL-4 is an anti-inflammatory and analgesic cytokine that induces opioid receptor transcription. We investigated IL-4 knockout (ko mice to characterize their pain behavior before and after chronic constriction injury (CCI of the sciatic nerve as a model for neuropathic pain. We investigated opioid responsivity and measured cytokine and opioid receptor gene expression in the peripheral and central nervous system (PNS, CNS of IL-4 ko mice in comparison with wildtype (wt mice. Naïve IL-4 ko mice displayed tactile allodynia (wt: 0.45 g; ko: 0.18 g; p<0.001, while responses to heat and cold stimuli and to muscle pressure were not different. No compensatory changes in the gene expression of tumor necrosis factor-alpha (TNF, IL-1β, IL-10, and IL-13 were found in the PNS and CNS of naïve IL-4 ko mice. However, IL-1β gene expression was stronger in the sciatic nerve of IL-4 ko mice (p<0.001 28 days after CCI and only IL-4 ko mice had elevated IL-10 gene expression (p = 0.014. Remarkably, CCI induced TNF (p<0.01, IL-1β (p<0.05, IL-10 (p<0.05, and IL-13 (p<0.001 gene expression exclusively in the ipsilateral spinal cord of IL-4 ko mice. The compensatory overexpression of the anti-inflammatory and analgesic cytokines IL-10 and IL-13 in the spinal cord of IL-4 ko mice may explain the lack of genotype differences for pain behavior after CCI. Additionally, CCI induced gene expression of μ, κ, and δ opioid receptors in the contralateral cortex and thalamus of IL-4 ko mice, paralleled by fast onset of morphine analgesia, but not in wt mice. We conclude that a lack of IL-4 leads to mechanical sensitivity; the compensatory hyperexpression of analgesic cytokines and opioid receptors after CCI, in turn, protects IL-4 ko mice from enhanced pain behavior after nerve lesion.

  19. The role of IL 23 in the treatment of psoriasis.

    Science.gov (United States)

    Puig, Lluís

    2017-06-01

    The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis. Human IL-23 is primarily produced by antigen-presenting cells and induces and maintains differentiation of Th17 cells and Th22 cells, a primary cellular source of proinflammatory cytokines such as IL-17 and IL-22, which mediate the epidermal hyperplasia, keratinocyte immune activation and tissue inflammation inherent in psoriasis. Agents that target the p40 subunit common to both IL-12 and IL-23 have shown robust clinical activity, but selectivity for IL-23p19 could offer advantages in efficacy and safety with respect to anti-p40 blockade. Areas covered: Relevant references regarding the role of the IL-23/IL-17 pathway in the pathogenesis of psoriasis/psoriatic arthritis and clinical trials with IL-23p40 and IL-23p19 blocking agents were obtained through a literature search in MEDLINE/Pubmed for articles published until November 2016. Moreover, ongoing registered clinical trials (RCTs) of moderate-to-severe psoriasis and psoriatic arthritis were searched through clinicaltrials.gov website, and a manual search was made for pertinent communications at the 2016 American Academy of Dermatology and European Academy of Dermatology and Venereology meetings. Expert commentary: There are potential advantages in selective blockade of the IL23-specific p19 subunit with respect to distal blockade of IL-17A or its receptor. Acting upstream in the IL-23/IL-17 cytokine pathway is likely to reduce the expression of multiple pro-inflammatory cytokines acting on keratinocytes -including IL-17F, IL-21 and IL-22-, in addition to IL-17A. On the other hand, safety data thus far suggest that these drugs might be devoid of some adverse effects of IL-17A blockade that seem to be class related, such as mucocutaneous Candida infections or triggering or worsening of inflammatory bowel disease. Specific IL-23p19 blockade with high-affinity monoclonal antibodies seems to be able to induce long

  20. Curcumin induces M2 macrophage polarization by secretion IL-4 and/or IL-13.

    Science.gov (United States)

    Gao, Shanshan; Zhou, Juan; Liu, Na; Wang, Lijun; Gao, Qiyue; Wu, Yan; Zhao, Qiang; Liu, Peining; Wang, Shun; Liu, Yan; Guo, Ning; Shen, Yan; Wu, Yue; Yuan, Zuyi

    2015-08-01

    To address the underlying mechanisms by which curcumin facilitates M2 phenotype polarization of macrophages and its roles in the protective effects during experimental autoimmune myocarditis (EAM). The expression of classic M2 markers, including macrophage mannose receptor (MMR), arginase-1 (Arg-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ) was upregulated in curcumin-treated Raw264.7 macrophages. Curcumin increased interleukin-4 (IL-4) and interleukin-13 (IL-13) mRNA expression and protein secretion. Curcumin notably increased STAT6 phosphorylation. Leflunomide, a STAT6 inhibitor, and IL-4 and/or IL-13 neutralizing antibodies antagonized the induction of MMR, Arg-1 and PPAR-γ by curcumin in Raw264.7 cells. In vivo, 6-week old male Lewis rats were used to induce EAM and orally administrated with curcumin or corn oil for 3weeks after myosin injection. Cardiac functional parameters, including left ventricular fractional shortening (LVFS), ejection fraction (EF), left ventricular end-systolic diameter (LVEDs) and heart rate (HR) were significantly improved by curcumin treatment. Curcumin also reduced the inflammatory cell infiltration and myocardial mRNA levels of interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS). Meanwhile, the myocardial mRNA levels of MMR and Arg-1 were markedly up-regulated by curcumin. Immunofluorescence assay showed that the number of CD68(+) MMR(+) and CD68(+) Arg-1(+) double positive macrophages in curcumin-treated myocardial tissue was significantly higher than untreated control. The number of CD68(+) iNOS(+) double positive macrophages was increased obviously in EAM group, but decreased markedly by curcumin treatment. Taken together, these results show that curcumin induces macrophage M2 polarization by secretion of IL-4 and/or IL-13. Curcumin ameliorates EAM by reducing infiltration inflammatory macrophages and by polarizing M0 and M1 macrophages to M2 phenotype. Copyright © 2015 Elsevier Ltd. All rights

  1. Association of IL8 and IL10 gene allelic variants with ischemic stroke risk and prognosis

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    Kucherenko A. M.

    2014-05-01

    Full Text Available Aim. Evaluating a role of IL8 gene –781 C/T, and IL10 gene –592C/A polymorphisms as genetic markers of ischemic stroke risk. Methods. A case group consisted of 183 patients with ischemic stroke, which were treated in the Brain Vascular Pathology unit of SI «Institute of Gerontology of NAMS of Ukraine». A control group included 88 healthy individuals older than 65 years without any history of ischemic stroke. Genotyping was performed using PCR followed by restriction fragment length polymorphism analysis. Results. Significantly (P < 0,05 higher frequency of IL8 –781T allele carriers in the case group (81,6 % comparing to the control (70,1% was revealed. –781T allele carriers have nearly 2-fold increased ischemic stroke development risk (OR = 1.886; 95 % CI: 1.041–3.417. Significantly (P < 0,05 higher frequency of IL10 gene –592C allele carriers was observed in the patients with ischemic stroke (98,2% comparing to the control (90,7 %. The ischemic stroke development risk in such individuals is 5-fold increased (OR = 5.71; 95 % CI: 1.48–22.11. It was revealed that –592C allele homozygotes with ischemic stroke have more than 2-fold higher improvement (according to the Rankin scale chances during the first fortnight of treatment (OR = 2,76; 95 % CI: 1,26–6,07. Conclusions. On the basis of the obtained significant differences, IL8 gene –781T and IL10 gene –592C variants may be considered the factors of ischemic stroke hereditary susceptibility. Besides, IL10 gene –592CC genotype is a genetic marker of the patients state positive dynamics during first two weeks of treatment.

  2. Expression of IL-1α and IL-6 is Associated with Progression and Prognosis of Human Cervical Cancer.

    Science.gov (United States)

    Song, Zhiwang; Lin, Yun; Ye, Xiaojuan; Feng, Chan; Lu, Yonglin; Yang, Guang; Dong, Chunyan

    2016-11-20

    BACKGROUND IL-1α and IL-6 are associated with the prognosis of a wide range of cancers, but their value in cervical cancer remains controversial. The aim of this study was to investigate the expression of IL-1α and IL-6 in cervical cancer and their significance in clinical prognosis. MATERIAL AND METHODS The expression of IL-1α and IL-6 in 105 formalin-fixed, paraffin-embedded cervical cancer tissues and adjacent non-tumor tissues was examined by immunohistochemistry. The results were semi-quantitatively scored and analyzed by chi-square test. Patient overall survival (OS) data was collected by follow-up and analyzed by Kaplan-Meier analysis. RESULTS The expression level of both IL-1α and IL-6 in cervical cancer tissue was higher than in adjacent non-tumor tissues (p<0.05). IL-1α expression was shown to be correlated with tumor size, FIGO histology grade, lymph node metastasis, stromal invasion, and tumor differentiation (p<0.05). IL-6 expression was shown to be correlated with tumor size, FIGO histology grade, and tumor differentiation (p<0.05). Patients with positive expression of IL-1α or IL-6 tended to have much shorter survival times than patients with negative expression. In addition, a multivariate Cox regression analysis demonstrated that IL-1α expression and lymph node metastasis were independent predictors of OS in cervical cancer patients. CONCLUSIONS The expression of IL-1α was significantly associated with tumor size, FIGO histology grade, lymph node metastasis, stromal invasion, and tumor differentiation. The expression of IL-6 was significantly associated with tumor size, FIGO histology grade, and tumor differentiation. Positive IL-1α and IL-6 expression was significantly correlated with poor prognosis. They may be considered valuable biomarkers for prognosis and potential therapeutic targets for cervical cancer.

  3. IL-27 Activates Human Trophoblasts to Express IP-10 and IL-6: Implications in the Immunopathophysiology of Preeclampsia

    Directory of Open Access Journals (Sweden)

    Nanlin Yin

    2014-01-01

    Full Text Available Purpose. To investigate the effects of IL-27 on human trophoblasts and the underlying regulatory signaling mechanisms in preeclampsia. Methods. The expression of IL-27 and IL-27 receptor (WSX-1 was studied in the placenta or sera from patients with preeclampsia. In vitro, we investigated the effects of IL-27 alone or in combination with inflammatory cytokine tumor necrosis factor (TNF-α on the proinflammatory activation of human trophoblast cells (HTR-8/SVneo and the underlying intracellular signaling molecules. Results. The expression of IL-27 and IL-27 receptor α (WSX-1 was significantly elevated in the trophoblastic cells from the placenta of patients with preeclampsia compared with control specimens. In vitro, IL-27 could induce the expression of inflammatory factors IFN-γ-inducible protein 10 (CXCL10/IP-10 and IL-6 in trophoblasts, and a synergistic effect was observed in the combined treatment of IL-27 and TNF-α on the release of IP-10 and IL-6. Furthermore, the production of IP-10 and IL-6 stimulated by IL-27 was differentially regulated by intracellular activation of phosphatidylinositol 3-OH kinase-AKT, p38MAPK, and JAK/STAT pathways. Conclusions. These results provide a new insight into the IL-27-activated immunopathological effects mediated by distinct intracellular signal transduction molecules in preeclampsia.

  4. Genetic regulation ofIL1RL1methylation and IL1RL1-a protein levels in asthma.

    Science.gov (United States)

    Dijk, F Nicole; Xu, Chengjian; Melén, Erik; Carsin, Anne-Elie; Kumar, Asish; Nolte, Ilja M; Gruzieva, Olena; Pershagen, Goran; Grotenboer, Neomi S; Savenije, Olga E M; Antó, Josep Maria; Lavi, Iris; Dobaño, Carlota; Bousquet, Jean; van der Vlies, Pieter; van der Valk, Ralf J P; de Jongste, Johan C; Nawijn, Martijn C; Guerra, Stefano; Postma, Dirkje S; Koppelman, Gerard H

    2018-03-01

    Interleukin-1 receptor-like 1 ( IL1RL1 ) is an important asthma gene. (Epi)genetic regulation of IL1RL1 protein expression has not been established. We assessed the association between IL1RL1 single nucleotide polymorphisms (SNPs), IL1RL1 methylation and serum IL1RL1-a protein levels, and aimed to identify causal pathways in asthma.Associations of IL1RL1 SNPs with asthma were determined in the Dutch Asthma Genome-wide Association Study cohort and three European birth cohorts, BAMSE (Children/Barn, Allergy, Milieu, Stockholm, an Epidemiological survey), INMA (Infancia y Medio Ambiente) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy), participating in the Mechanisms of the Development of Allergy study. We performed blood DNA IL1RL1 methylation quantitative trait locus (QTL) analysis (n=496) and (epi)genome-wide protein QTL analysis on serum IL1RL1-a levels (n=1462). We investigated the association of IL1RL1 CpG methylation with asthma (n=632) and IL1RL1-a levels (n=548), with subsequent causal inference testing. Finally, we determined the association of IL1RL1-a levels with asthma and its clinical characteristics (n=1101). IL1RL1 asthma-risk SNPs strongly associated with IL1RL1 methylation (rs1420101; p=3.7×10 -16 ) and serum IL1RL1-a levels (p=2.8×10 -56 ). IL1RL1 methylation was not associated with asthma or IL1RL1-a levels. IL1RL1-a levels negatively correlated with blood eosinophil counts, whereas there was no association between IL1RL1-a levels and asthma.In conclusion, asthma-associated IL1RL1 SNPs strongly regulate IL1RL1 methylation and serum IL1RL1-a levels, yet neither these IL1RL1- methylation CpG sites nor IL1RL1-a levels are associated with asthma. Copyright ©ERS 2018.

  5. Il valore dell'eBook

    Directory of Open Access Journals (Sweden)

    Nicola Cavalli

    2013-03-01

    Full Text Available ItQuanto vale un e-book? Quale valore percepisce chi compra e usa gli e-book? Comprare un libro o un e-book è una scelta che i lettori oggi si trovano a fare quotidianamente: la diffusione degli e-book reader a prezzi accessibili e la proposta sempre più varia dei piccoli e grandi editori sta cambiando la percezione del valore commerciale dell'oggetto libro e del valore attribuito dal consumatore finale al lavoro di intermediazione delle case editrici e della distribuzione. Sorgono sistemi "alternativi" di condivisione dei testi digitali, che sfruttano la rete Internet, celebrati come democratici o demonizzati come pirateria illegale, ma sicuramente rispondenti a quello che è il cambio di prospettiva, di percezione, di abitudini di consumo del lettore. Quanto si può parlare, dunque, di pirateria nel mercato degli e-book? E quanto, invece, è importante che l'industria editoriale tenga in considerazione la risposta del consumatore? La presente ricerca si è posta l’obiettivo di svolgere una indagine esplorativa su questi temi, che stanno assumendo un rilievo sempre maggiore all’interno dell’opinione pubblica, e che sono destinati in futuro ad incidere in modo sempre più diretto sull’evoluzione economica e professionale dell’intero settore editoriale. L’indagine ha visto, in questa prima fase, l’utilizzo di un questionario diffuso online sui social network, in siti e forum dedicati alla lettura, attraverso mailing list di gruppi di interesse, con il primo obiettivo di precisare il profilo di quell’avanguardia di lettori forti e che si muovono agilmente tra il cartaceo e il digitale, raccogliere informazioni rispetto alle loro abitudini di ricerca di nuove letture e descriverne le dinamiche di matchmaking preliminari all’acquisto. In aggiunta, si è indagata la consistenza di pratiche di prestito e condivisione dei libri, l’appoggio a sistemi tradizionali, come quello bibliotecario, o la decisa svolta verso sistemi di

  6. LINGUA ITALIANA E IDENTITÀ: IL CASO DEL FUMETTO PANINARO

    African Journals Online (AJOL)

    User

    Nel 1986 uscì nelle sale cinematografiche italiane il film Italian fast food per la regia di. Lodovico Gasperini. .... “Parola-chiave dei gerghi giovanili; nata con il fast-food (del bar Panino a Milano, i cui frequentatori abituali si ... paninarese è un linguaggio studentesco milanese nato nei cosiddetti licei “bene” come il Volta e nei ...

  7. IL-6 Alters Osteocyte Signaling toward Osteoblasts but Not Osteoclasts

    NARCIS (Netherlands)

    Bakker, A; Kulkarni, R.; Klein-Nulend, J.; Lems, W.F.

    2014-01-01

    Mechanosensitive osteocytes regulate bone mass in adults. Interleukin 6 (IL-6), such as present during orthodontic tooth movement, also strongly affects bone mass, but little is known about the effect of IL-6 on osteocyte function. Therefore we aimed to determine in vitro whether IL-6 affects

  8. IL-6 alters osteocyte signaling toward osteoblasts but not osteoclasts

    NARCIS (Netherlands)

    Bakker, A.D.; Kulkarni, R.N.; Klein-Nulend, J.; Lems, W.F.

    2014-01-01

    Mechanosensitive osteocytes regulate bone mass in adults. Interleukin 6 (IL-6), such as present during orthodontic tooth movement, also strongly affects bone mass, but little is known about the effect of IL-6 on osteocyte function. Therefore we aimed to determine in vitro whether IL-6 affects

  9. IL-6 alters osteocyte signaling toward osteoblasts but not osteoclasts.

    Science.gov (United States)

    Bakker, A D; Kulkarni, R N; Klein-Nulend, J; Lems, W F

    2014-04-01

    Mechanosensitive osteocytes regulate bone mass in adults. Interleukin 6 (IL-6), such as present during orthodontic tooth movement, also strongly affects bone mass, but little is known about the effect of IL-6 on osteocyte function. Therefore we aimed to determine in vitro whether IL-6 affects osteocyte mechanosensitivity, and osteocyte regulation of osteoclastogenesis and osteoblast differentiation. MLO-Y4 osteocytes were incubated with/without IL-6 (1 or 10 pg/mL) for 24 hr. Subsequently, osteocytes were subjected to mechanical loading by pulsating fluid flow (PFF) for 1 hr. Mouse osteoclast precursors were cultured for 7 days on top of IL-6-treated osteocytes. Conditioned medium from osteocytes treated with/without IL-6 was added to MC3T3-E1 pre-osteoblasts for 14 days. Exogenous IL-6 (10 pg/mL) did not alter the osteocyte response to PFF. PFF significantly enhanced IL-6 production by osteocytes. IL-6 enhanced Rankl expression but reduced caspase 3/7 activity by osteocytes, and therefore did not affect osteocyte-stimulated osteoclastogenesis. Conditioned medium from IL-6-treated osteocytes reduced alkaline phosphatase (ALP) activity and Runx2 expression in osteoblasts, but increased expression of the proliferation marker Ki67 and osteocalcin. Our results suggest that IL-6 is produced by shear-loaded osteocytes and that IL-6 may affect bone mass by modulating osteocyte communication toward osteoblasts.

  10. Potential Involvement of IL-17F in Asthma

    Directory of Open Access Journals (Sweden)

    Kyoko Ota

    2014-01-01

    Full Text Available The expression of IL-17F is seen in the airway of asthmatics and its level is correlated with disease severity. Several studies have demonstrated that IL-17F plays a pivotal role in allergic airway inflammation and induces several asthma-related molecules such as CCL20. IL-17F-induced CCL20 may attract Th17 cells into the airway resulting in the recruitment of additional Th17 cells to enhance allergic airway inflammation. We have recently identified, for the first time, that bronchial epithelial cells are its novel cell source in response to IL-33 via ST2-ERK1/2-MSK1 signaling pathway. The receptor for IL-17F is the heterodimeric complex of IL-17RA and IL-17RC, and IL-17F activates many signaling pathways. In a case-control study of 867 unrelated Japanese subjects, a His161 to Arg161 (H161R substitution in the third exon of the IL-17F gene was associated with asthma. In atopic patients with asthma, prebronchodilator baseline FEV1/FVC values showed a significant association with the H161R variant. Moreover, this variant is a natural antagonist for the wild-type IL-17F. Moreover, IL-17F is involved in airway remodeling and steroid resistance. Hence, IL-17F may play an orchestrating role in the pathogenesis of asthma and may provide a valuable therapeutic target for development of novel strategies.

  11. “Economic heritage impact assessment” come strumento per valutare gli impatti dei grandi progetti di riqualificazione delle città costiere siti Unesco. Il caso studio di Torre Annunziata nel golfo di Napoli

    Directory of Open Access Journals (Sweden)

    Mariarosaria Angrisano

    2015-12-01

    Full Text Available Quest’articolo parte dallo studio delle città portuali storiche, siti UNESCO, che oggi affrontano la sfida della riqualificazione dei waterfront urbani attraverso la conservazione del patrimonio culturale e paesaggistico. Le raccomandazioni sull’ “Historic Urban Landscape”, e gli strumenti operativi promossi dall’ICOMOS “Guidance on Heritage Impact Assessments for Cultural World Heritage Properties” del 2011, si configurano come le più recenti disposizioni concernenti la conservazione, protezione e valorizzazione del patrimonio culturale (Fusco Girard, 2010. La Guida ICOMOS è stata considerata lo strumento più adatto per valutare gli impatti dei grandi progetti di riqualificazione dei waterfront urbani sul patrimonio culturale. Per comprendere al meglio tale strumento è stata fatta un’applicazione per valutare gli impatti del Grande Progetto Pompei sul waterfront di Torre Annunziata, città costiera nel Golfo di Napoli sito UNESCO. A questa fase di analisi segue una riflessione su come migliorare l’Heritage Impact Assessment, come strumento capace di valutare non soltanto gli impatti culturali ma anche quelli economici, per parlare di “economia del patrimonio culturale”. La proposta ultima è quella di affiancare al processo di “Heritage Impact Assessment” una valutazione degli impatti economici, attraverso un’analisi costi-benefici, per quantificare in termini monetari la convenienza degli investimenti nella conservazione del patrimonio storico urbano delle città costiere, proponendo una “Economic Heritage Impact Assessment” (EHIA. Tale metodo, elaborato dall’autrice all’interno della tesi di dottorato “Il paesaggio storico urbano delle città costiere: sfide e opportunità. Il caso Torre Annunziata”, offre la possibilità di superare la sola valutazione degli impatti culturali proposta dall’ICOMOS.

  12. IL-23/IL-17/G-CSF pathway is associated with granulocyte recruitment to the lung during African swine fever.

    Science.gov (United States)

    Karalyan, Z; Voskanyan, H; Ter-Pogossyan, Z; Saroyan, D; Karalova, E

    2016-10-15

    The interleukin (IL)-23/IL-17 pathway plays a crucial role in various forms of inflammation but its function in acute African swine fever (ASF) is not well understood. Thus, in this study, we aimed to find out whether IL-23/IL-17/G-CSF is released in acute ASF and what function it may have. The present study revealed that the production of IL-17 and IL-23 were significantly increased in the sera of ASFV infected pigs. Using ELISA, we found that the serum levels of IL-23 and IL-17 have overexpressed in ASF virus infected pigs compared with healthy controls. The levels of IL-17 and IL-23 increase in the early stages and the levels of G-CSF and C - reactive protein in the later stages of ASF. Simultaneously, with the increase of the levels of IL-23/IL-17 extravasation of granular leukocytes in the tissue (diapedesis) is observed. Diapedesis can explain the neutropenia that we identified previously in the terminal stages of ASF. The increase in serum levels of IL-23/IL-17 is preceded by enhanced migration of neutrophils in tissues, and the last one is preceded by neutropenia. The increase in serum levels of G-CSF has compensatory nature, directed on stimulation of proliferation of granulocytes. Taken together, our results revealed an overexpression of the IL-23/IL-17 axis in the ASF virus infected pigs, suggesting that it may be a crucial pathway in the diapedesis at ASF. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. IL-17F induces IL-6 via TAK1-NFκB pathway in airway smooth muscle cells.

    Science.gov (United States)

    Nakajima, Masayuki; Kawaguchi, Mio; Ota, Kyoko; Fujita, Junichi; Matsukura, Satoshi; Huang, Shau-Ku; Morishima, Yuko; Ishii, Yukio; Satoh, Hiroaki; Sakamoto, Tohru; Hizawa, Nobuyuki

    2017-06-01

    Interleukin (IL)-17F plays a critical role in the pathophysiology of asthma. However, the precise role of IL-17F in airway smooth muscle cells (ASMCs) and its regulatory mechanisms remain to be defined. Therefore, we sought to investigate the expression of IL-6 by IL-17F and the involvement of transforming growth factor β-activated kinase 1 (TAK1) and nuclear factor (NF)-κB by in ASMCs. ASMCs were cultured in the presence or absence of IL-17F. The expression of IL-6 gene and protein was analyzed using real-time PCR and ELISA, and the activation of TAK1 and NF-κB was detected by Western blotting. The effect of TAK1 inhibitor 5Z-7-oxozeaenol and NF-κB inhibitor BAY 11-7082 on the expression of IL-6 was investigated. Finally, the short interfering RNAs (siRNAs) targeting TAK1 and a subunit of NF-κB, p65 were transfected into ASMCs. The expression of IL-6 gene and protein was significantly induced by IL-17F. IL-17F activated TAK1 and NF-κB in ASMCs. Transfection of siRNAs targeting TAK1 abolished IL-17F-induced phosphorylation of p65. Both 5Z-7-oxozeaenol and BAY 11-7082 significantly inhibited IL-17F-induced IL-6 production in a dose-dependent manner. Similarly, transfection of the cells with siRNAs targeting TAK1 and p65 inhibited the expression of IL-6. Collectively, these results provided evidence supporting the potential importance of the Th17-ASMCs crosstalk via the IL-17F-IL-6 axis in airway inflammation and as a candidate pharmacological target for airway inflammatory diseases such as asthma. © 2017 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

  14. Kinetic analysis of interleukin 2 (IL-2) production and expression of IL-2 receptors by uraemic and normal lymphocytes

    DEFF Research Database (Denmark)

    Langhoff, E; Hofmann, B; Ødum, Niels

    1987-01-01

    The in vitro immune response of lymphocytes from uraemic patients was studied by comparing the in vitro kinetics of interleukin 2 (IL-2) production, the mitogen-induced proliferative response, and the expression of IL-2 receptors by T lymphocytes. The IL-2 production in 26 uraemic cell cultures...

  15. IL-7R expression and IL-7 signaling confer a distinct phenotype on developing human B-lineage cells

    NARCIS (Netherlands)

    Nodland, Sonja E.; Berkowska, Magdalena A.; Bajer, Anna A.; Shah, Nisha; de Ridder, Dick; van Dongen, Jacques J. M.; LeBien, Tucker W.; van Zelm, Menno C.

    2011-01-01

    IL-7 is an important cytokine for lymphocyte differentiation. Similar to what occurs in vivo, human CD19(+) cells developing in human/murine xenogeneic cultures show differential expression of the IL-7 receptor alpha (IL-7R alpha) chain (CD127). We now describe the relationship between CD127

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

    Directory of Open Access Journals (Sweden)

    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.

  17. TNF, IL-1 and IL-6 in circulating blood after total-body and localized irradiation in rats

    NARCIS (Netherlands)

    Haveman, J.; Geerdink, A. G.; Rodermond, H. M.

    1998-01-01

    The levels of TNF, IL-1 and IL-6 in circulating blood of female WAG/Rij rats were assessed both after total-body irradiation (TBI) and localized irradiation of the right hind leg. The results show that enhanced levels of IL-1 in the circulation reflect a stress situation presumably resulting from

  18. Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17

    DEFF Research Database (Denmark)

    Muñoz, Melba; Heimesaat, Markus M; Danker, Kerstin

    2009-01-01

    Peroral infection with Toxoplasma gondii leads to the development of small intestinal inflammation dependent on Th1 cytokines. The role of Th17 cells in ileitis is unknown. We report interleukin (IL)-23-mediated gelatinase A (matrixmetalloproteinase [MMP]-2) up-regulation in the ileum of infected...... mice. MMP-2 deficiency as well as therapeutic or prophylactic selective gelatinase blockage protected mice from the development of T. gondii-induced immunopathology. Moreover, IL-23-dependent up-regulation of IL-22 was essential for the development of ileitis, whereas IL-17 was down...

  19. Observation on CEA and IL-6 contents in gastric juice

    International Nuclear Information System (INIS)

    Jiang Zhonglin

    2003-01-01

    Objective: To study the changes of CEA and IL-6 contents in blood and gastric juice in patients with gastric cancer and gastritis. Methods: CEA and IL-6 contents in blood and gastric juice were measured with RIA in 60 patients and 30 controls. Results: Gastric juice CEA and IL-6 contents in patients with gastric carcinoma were significantly higher than those in the controls (p < 0.001), however, CEA and IL-6 contents in patients with gastritis and controls were not much different. Conclusion: Gastric juice CEA and IL-6 assay is of diagnostic significance in patients with gastric malignant tumor

  20. Effect of interleukin (IL-35 on IL-17 expression and production by human CD4+ T cells

    Directory of Open Access Journals (Sweden)

    Kosuke Okada

    2017-02-01

    Full Text Available Background Interleukin (IL-17 produced by mainly T helper 17 (Th17 cells may play an important destructive role in chronic periodontitis (CP. Thus, anti-inflammatory cytokines, such as IL-35, might have a beneficial effect in periodontitis by inhibiting differentiation of Th17 cells. Th17 differentiation is regulated by the retinoic acid receptor-related orphan receptor (ROR α (encoded by RORA and RORγt (encoded by RORC. However, the role of IL-35 in periodontitis is not clear and the effect of IL-35 on the function of Th17 cells is still incompletely understood. Therefore, we investigated the effects of IL-35 on Th17 cells. Methods Peripheral blood mononuclear cells (PBMCs were sampled from three healthy volunteers and three CP patients and were analyzed by flow cytometry for T cell population. Th17 cells differentiated by a cytokine cocktail (recombinant transforming growth factor-β, rIL-6, rIL-1β, anti-interferon (IFN-γ, anti-IL-2 and anti-IL-4 from PBMCs were cultured with or without rIL-35. IL17A (which usually refers to IL-17, RORA and RORCmRNA expression was analyzed by quantitative polymerase chain reaction, and IL-17A production was determined by enzyme-linked immunosorbent assay. Results The proportion of IL-17A+CD4+ slightly increased in CP patients compared with healthy controls, however, there were no significant differences in the percentage of IL-17A+CD4+ as well as IFN-γ+CD4+ and Foxp3+CD4+ T cells between healthy controls and CP patients. IL17A, RORA and RORC mRNA expression was significantly increased in Th17 cells induced by the cytokine cocktail, and the induction was significantly inhibited by addition of rIL-35 (1 ng/mL. IL-17A production in Th17 cells was significantly inhibited by rIL-35 addition (1 ng/mL. Discussion The present study suggests that IL-35 could directly suppress IL-17 expression via RORα and RORγt inhibition and might play an important role in inflammatory diseases such as periodontitis.

  1. Il cavo orale nel paziente obeso

    OpenAIRE

    Faggella, Antonella

    2008-01-01

    Le condizioni di sovrappeso ed obesità anche in età evolutiva sono aumentate negli ultimi decenni al punto che, secondo l'Organizzazione Mondiale della Sanità, sono diventate un problema di salute pubblica in tutti i Paesi occidentali. Questa tesi è nata nell’obiettivo di individuare caratteristiche odontostomatologiche in pazienti affetti da obesità; il gruppo campione(80 pazienti, età media 10,5 anni) è stato suddiviso in due sottogruppi: sottogruppo A comprendente 54 pazienti affetti da...

  2. Il nuovo volto dell'universo

    CERN Document Server

    Radicati di Brozolo, L A

    1994-01-01

    Quale realtà indaga la più avanzata scienza odierna? Con quali strumenti concettuali opera? Dai contributi di alcuni fisici italiani emerge un'immagine del mondo radicalmente rinnovata. Petrillo, R. Rozzi, G. Sapelli, A. Savignano, L. Sicca, F. Silari, P. Toninelli, M. Vasta, G. Zanetti. mal di mare. Il velista che dispone di una imbarcazione progettata e equipaggiata secondo gli standard degli anni '90, con un'accurata preparazione, sarà in grado di unirsi alla schiera di navigatori famosi che sono sopravvissuti a condizioni ambientali proibitive.

  3. Mercenario della ricerca evoluzione dello studioso di fisica tra il 1900 e il 2000

    CERN Document Server

    Sironi, Giorgio

    2015-01-01

    In meno di un secolo la percezione della ricerca da parte del grande pubblico e il modo di praticarla sono profondamente cambiati. Il ricercatore, non più isolato e parte di una élite ristretta, oggi è quasi sempre inserito in gruppi strutturati, spesso numerosi. Questa impostazione, particolamente evidente in Fisica e Astrofisica, ha prodotto grandi progressi scientifici. In Italia però questi progressi rischiano di essere vanificati dalla perdurante mancanza di politiche organiche dedicate alla ricerca, sia pubblica che privata. Per un giovane dotato vale ancora la pena di puntare a fare ricerca?

  4. Hip Osteonecrosis Is Associated with Increased Plasma IL-33 Level

    Directory of Open Access Journals (Sweden)

    Jinhui Ma

    2017-01-01

    Full Text Available The recently discovered IL-33 as an IL-1 cytokine family member has been proved to be specifically released from osteonecrotic bones. We aimed to investigate the potential role of IL-33 in the development of osteonecrosis of femoral head (ONFH. Forty patients diagnosed with ONFH and forty age-, sex-, and body mass index- (BMI- matched healthy subjects were included in this prospective study between March 2016 and September 2016. A commercially available ELISA kit was used to test the level of plasma IL-33. The IL-33 levels were compared among different ARCO stages, CJFH types, and etiology groups. Plasma IL-33 levels were significantly higher in the ONFH patients than that in the control subjects. The levels of IL-33 did not differ significantly among the ONFH patients with different ARCO stages. The IL-33 levels of patients with CJFH type L3 were significantly higher than that of patients with types L1 and L2. No significant differences were observed in IL-33 levels between steroid-induced, alcohol-induced, and idiopathic patients. Our findings seem to indicate that IL-33 effects may be detrimental during ONFH, which appeared to be associated with the prognosis of ONFH. The IL-33 deserves particular attention in the pathogenesis of ONFH.

  5. Nutritional interventions and the IL-6 response to exercise.

    Science.gov (United States)

    Hennigar, Stephen R; McClung, James P; Pasiakos, Stefan M

    2017-09-01

    IL-6 is a pleiotropic cytokine with a wide range of biologic effects. In response to prolonged exercise, IL-6 is synthesized by contracting skeletal muscle and released into circulation. Circulating IL-6 is thought to maintain energy status during exercise by acting as an energy sensor for contracting muscle and stimulating glucose production. If tissue damage occurs, immune cells infiltrate and secrete cytokines, including IL-6, to repair skeletal muscle damage. With adequate rest and nutrition, the IL-6 response to exercise is attenuated as skeletal muscle adapts to training. However, sustained elevations in IL-6 due to repeated bouts of unaccustomed activities or prolonged exercise with limited rest may result in untoward physiologic effects, such as accelerated muscle proteolysis and diminished nutrient absorption, and may impair normal adaptive responses to training. Recent intervention studies have explored the role of mixed meals or carbohydrate, protein, ω-3 fatty acid, or antioxidant supplementation in mitigating exercise-induced increases in IL-6. Emerging evidence suggests that sufficient energy intake before exercise is an important factor in attenuating exercise-induced IL-6 by maintaining muscle glycogen. We detail various nutritional interventions that may affect the IL-6 response to exercise in healthy human adults and provide recommendations for future research exploring the role of IL-6 in the adaptive response to exercise.-Hennigar, S. R., McClung, J. P., Pasiakos, S. M. Nutritional interventions and the IL-6 response to exercise. © FASEB.

  6. IL-18: a key player in neuroinflammation and neurodegeneration?

    Science.gov (United States)

    Felderhoff-Mueser, Ursula; Schmidt, Oliver I; Oberholzer, Andreas; Bührer, Christoph; Stahel, Philip F

    2005-09-01

    Interleukin (IL)-18 is a potent inflammatory cytokine of the IL-1 family. It is synthesized as an inactive precursor (pro-IL-18), which is cleaved into its functionally active form by caspase-1. Resident cells of the CNS express IL-18 and caspase-1 constitutively, thus providing a local IL-18-dependent immune response. Recent studies have highlighted a crucial role for IL-18 in mediating neuroinflammation and neurodegeneration in the CNS under pathological conditions, such as bacterial and viral infection, autoimmune demyelinating disease, and hypoxic-ischemic, hyperoxic and traumatic brain injuries. This review provides a synopsis of the current knowledge of IL-18-dependent mechanisms of action during acute neurodegeneration in immature and adult brains.

  7. 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.

    Directory of Open Access Journals (Sweden)

    Margit Hørup Larsen

    Full Text Available 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.We performed an initial genome-wide association study using Affymetrix Human Mapping 500 K GeneChip® to screen 130 healthy individuals of Danish descent. The levels of IL-6, IL-8, IL-10, IL-1ra and TNF-α in 24-hour LPS-stimulated whole blood samples were compared within different genotypes. The 152 most significant SNPs were replicated using Illumina Golden Gate® GeneChip in an independent cohort of 186 Danish individuals. Next, 9 of the most statistical significant SNPs were replicated using PCR-based genotyping in an independent cohort of 400 Danish individuals. All results were analyzed in a combined study among the 716 Danish individuals.Only one marker of the 500 K Gene Chip in the discovery study showed a significant association with LPS-induced IL-1ra cytokine levels after Bonferroni correction (P<10(-7. However, this SNP was not associated with the IL-1ra cytokine levels in the replication dataset. No SNPs reached genome-wide significance for the five cytokine levels in the combined analysis of all three stages.The associations between the genetic variants and the LPS-induced IL-6, IL-8, IL-10, IL-1ra and TNF-α cytokine levels were not significant in the meta-analysis. This present study does not support a strong genetic effect of LPS-stimulated cytokine production; however, the potential for type II errors should be considered.

  8. Association analysis of IL10, TNF-α and IL23R-IL12RB2 SNPs with Behçet's disease risk in Western Algeria

    Directory of Open Access Journals (Sweden)

    Ouahiba eKhaib Dit Naib

    2013-10-01

    Full Text Available Objective: We have conducted the first study of the association of interleukin (IL-10, tumor necrosis factor alpha (TNF-α and IL23R-IL12RB2 regionSNPswith Behçet's disease (BD in Western Algeria. Methods: A total of 51 BD patients and 96 unrelated controls from West region of Algeria were genotyped by direct sequencing for 11 SNPs including 2 SNPsfrom the IL10 promoter [c.-819T>C (rs1800871, c.-592A>C (rs1800872], 6 SNPs from the TNF-α promoter [c.-1211T>C (rs1799964, c.-1043C>A (rs1800630, c.-1037C>T (rs1799724, c.-556G>A (rs1800750, c.-488G>A (rs1800629 and c.-418G>A (rs361525], and 3 SNPs from the IL23R-IL12RB2 region [g.67747415A>C (rs12119179, g.67740092G>A (rs11209032 and g.67760140T>C (rs924080]. Results: The minor alleles c.-819T and c.-592A were significantly associated with BD (OR= 2.18; 95% CI 1.28-3.73, p = 0.003; whereas, there was weaker association between TNF-αpromoter SNPs or IL23R-IL12RB2 region and disease risk.Conclusion: Unlike the TNF-αand the IL23R-IL12RB2 region SNPs, the two IL10 SNPs were strongly associated with BD. The -819T, and -592A alleles and the -819TT, -819CT, and -592AA and -592CA genotypes seem to be highly involved in the risk of developing of BD in the population of Western Algeria.

  9. Introducing an ILS methodology into research reactors

    International Nuclear Information System (INIS)

    Lorenzo, N. de; Borsani, R.C.

    2003-01-01

    Integrated Logistics Support (ILS) is the managerial organisation that co-ordinates the activities of many disciplines to develop the supporting resources (training, staffing, designing aids, equipment removal routes, etc) required by technologically complex systems. The application of an ILS methodology in defence projects is described in several places, but it is infrequently illustrated for other areas; therefore the present paper deals with applying this approach to research reactors under design or already in operation. Although better results are obtained when applied since the very beginning of a project, it can be applied successfully in facilities already in operation to improve their capability in a cost-effective way. In applying this methodology, the key objectives shall be previously identified in order to tailor the whole approach. Generally in high power multipurpose reactors, obtaining maximum profit at the lowest possible cost without reducing the safety levels are key issues, while in others the goal is to minimise drawbacks like spurious shutdowns, low quality experimental results or even to reduce staff dose to ALARA values. These items need to be quantified for establishing a system status base line in order to trace the process evolution. Thereafter, specific logistics analyses should be performed in the different areas composing the system. RAMS (Reliability, Availability, Maintainability and Supportability), Manning, Training Needs, Supplying Needs are some examples of these special logistic assessments. The following paragraphs summarise the different areas, encompassed by this ILS methodology. Plant design is influenced focussing the designers? attention on the objectives already identified. Careful design reviews are performed only in an early design stage, being useless a later application. In this paper is presented a methodology including appropriate tools for ensuring the designers abide to ILS issues and key objectives through the

  10. The lysine deacetylase inhibitor givinostat inhibits ß-cell IL-1ß induced IL-1ß transcription and processing

    DEFF Research Database (Denmark)

    Dahllöf, Mattias Salling; Christensen, Dan P; Lundh, Morten

    2012-01-01

    breaks an autoinflammatory circuit by differentially preventing ß-cell expression of the ß-cell toxic inflammatory molecules IL-1ß and CXCL10 induced by single cytokines. Results: CXCL10 did not induce transcription of IL-1ß mRNA. IL-1ß induced ß-cell IL-1ß mRNA and both IL-1ß and IFN¿ individually...... induced Cxcl10 mRNA transcription. Givinostat inhibited IL-1ß-induced IL-1ß mRNA expression in INS-1 and rat islets and IL-1ß processing in INS-1 cells. Givinostat also reduced IFN¿ induced Cxcl10 transcription in INS-1 cells but not in rat islets, while IL-1ß induced Cxcl10 transcription was unaffected....../Interpretation: Inhibition of ß-cell IL-1ß expression and processing and Cxcl10 transcription contributes to the ß-cell protective actions of KDACi. In vitro ß-cell destructive effects of CXCL10 are not mediated via IL-1ß transcription. The differential proinflammatory actions of KDACs may be attractive novel drug targets...

  11. B cell activating factor (BAFF) selects IL-10-B cells over IL-10+B cells during inflammatory responses.

    Science.gov (United States)

    Ma, Ning; Zhang, Yu; Liu, Qilin; Wang, Zhiding; Liu, Xiaoling; Zhu, Gaizhi; Yu, Dandan; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Wang, Tianxiao; Ma, Yuanfang; Shen, Beifen; Li, Yan; Xiao, He; Wang, Renxi

    2017-05-01

    B cell activating factor (BAFF) regulates B cell maturation, survival, function, and plays a critical pathogenic role in autoimmune diseases. It remains unclear how BAFF affects IL-10 - B cells versus regulatory B cells (Bregs) in inflammatory responses. In this study, we found that IL-10-expressing Bregs decreased in lupus-prone MRL/lpr mice and experimental allergic encephalomyelitis (EAE) mice. On blockade of the effects of BAFF with TACI-IgG, IL-10 + Bregs were upregulated in MRL/lpr and EAE mice. In addition, BAFF expanded IL-10 + B cells over IL-10 - B cells under noninflammatory conditions in vitro, whereas it expanded IL-10 - B cells over IL-10 + B cells during inflammatory responses, such as stimulation with autoantigen and LPS. Finally, the selection of IL-10 - B cells over IL-10 + B cells by BAFF was dependent on BAFF receptors (BAFFR, TACI, and BCMA) that were upregulated by inflammatory responses. This study suggests that BAFF selects IL-10 - B cells over IL-10 + regulatory B cells via BAFF receptors in inflammatory responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Anti-IL-39 (IL-23p19/Ebi3) polyclonal antibodies ameliorate autoimmune symptoms in lupus-like mice

    Science.gov (United States)

    Wang, Xiaoqian; Zhang, Yu; Wang, Zhiding; Liu, Xiaoling; Zhu, Gaizhi; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Wang, Tianxiao; Shen, Beifen; Li, Yan; Xiao, He; Ma, Ning; Wang, Renxi

    2018-01-01

    The interleukin (IL)-12 family cytokines have been examined as therapeutic targets in the treatment of several autoimmune diseases. Our previous study showed that a novel IL-12 family cytokine, IL-39 (IL-23p19/Ebi3) mediates inflammation in lupus-like mice. In the present study, the effect of anti-mouse IL-39 polyclonal antibodies on autoimmune symptoms in lupus-like mice was investigated. Rabbit anti-mouse IL-39 polyclonal antibodies were produced by immunization with recombinant mouse IL-39, and purified using protein A chromatography. These antibodies were subsequently used to treat lupus-like mice. Flow cytometry, captured images, ELISA and H&E staining were used to determine the effect of anti-IL-39 polyclonal antibodies on inflammatory cells, autoantibody titers, proteinuria, infiltrating inflammatory cells and the structure of the glomerular region. The anti-IL-39 polyclonal antibodies effectively reduced the numbers of inflammatory cells, splenomegaly, autoantibody titers, proteinuria, infiltrating inflammatory cells, and restored the structure of the glomerular region in MRL/lpr mice. Taken together, these results suggested that anti-IL-39 polyclonal antibodies ameliorated autoimmune symptoms in lupus-like mice. Therefore, IL-39 may be used as a possible target for the treatment of systemic lupus erythematosus. PMID:29138852

  13. Detectable IL-8 and IL-10 in bronchoalveolar lavage fluid from preterm infants ventilated for respiratory distress syndrome.

    Science.gov (United States)

    Beresford, Michael W; Shaw, Nigel J

    2002-12-01

    Pro-inflammatory cytokines such as IL-8 play an important role in the inflammatory response to neonatal airway injury. Difficulty in detecting counter-regulatory cytokines such as IL-10 in lavage fluid from preterm infants led to the suggestion that its deficit may be a factor in the etiology of chronic lung disease of prematurity (CLD). The aim of the study was to determine IL-8 and IL-10 concentrations in lavage fluid from preterm infants ventilated for respiratory distress syndrome. Fifty infants Infants dying or developing CLD had a significant early rise in both cytokine concentrations. Compared with infants developing CLD, lavage IL-10 concentrations were significantly higher on d 1 among those not developing CLD but significantly lower on d 4 (p infants and its concentrations rise significantly over the first five postnatal days. In the same samples, IL-8 concentration also rises and this increase precedes the rise in IL-10.

  14. Il-legitimacy in the eyes of the il-legitimated

    DEFF Research Database (Denmark)

    Gerstroem, Anna

    2013-01-01

    these organizations. The purpose of this paper is to address this gap of knowledge by exploring how members of a bankrupted bank experience and handle attributions of organizational il-legitimacy: to investigate the phenomenon from an inside perspective - in the eyes of the people who undergo it. The paper has...

  15. Interleukin (IL)-17A and IL-17F and asthma in Saudi Arabia: mRNA ...

    African Journals Online (AJOL)

    Win-07

    (Th1 and Th2) lymphocytes play an important role in its pathophysiology. A third subset of helper T cells, named. Th17 cells, which exhibits functions distinct from Th1 and. Th2 cells and preferentially produces interleukin IL17, have been shown to plays a critical role in the pathophysiology of asthma (Benchetrit et al., 2002;.

  16. Effect of Bacillus thuringiensis parasporal toxin on stimulating of IL-2 and IL-5 cytokines production

    Directory of Open Access Journals (Sweden)

    Marzieh Soleimany

    2018-03-01

    Full Text Available Introduction:Bacillus thuringiensis, is a Gram-positive spore-forming bacterium that produces crystalline parasporal protein (Cry during sporulation. Some of these Cry toxins do not show cytotoxicity against insects but they are capable to kill some human and animal cancer cells. The aim of this study was to verify whether cytocidal parasporal of B thuringiensis strains have immunostimulatory activity on human peripheral blood mononuclear cells (PBMNC and to evaluate the ability of IL-2 and IL-5 production. Materials and methods: B. thuringiensis toxin with cytocidal activity was isolated and treated with proteinase K. PBMNC was cultured and treated with activated crystal proteins. We evaluated the ability of different cytokines production with Flow Cytometry. Results: In this study, immune stimulatory toxins Cry1 were distinguished. This toxin can stimulate production of cytokines IL-2 and stop production of IL-5. Discussion and conclusion: According to anti-cancer effect of B. thuringiensis toxins and also immune stimulatory effect, with more research these toxins can be introduced as immunotherapy drug in cancer treatment.

  17. Blood concentrations of the cytokines IL-1beta, IL-6, IL-10, TNF-alpha and IFN-gamma during experimentally induced swine dysentery

    Directory of Open Access Journals (Sweden)

    Jensen-Waern Marianne

    2008-08-01

    Full Text Available Abstract Background Knowledge of the cytokine response at infection with Brachyspira hyodysenteriae can help understanding disease mechanisme involved during swine dysentery. Since this knowledge is still limited the aim of the present study was to induce dysentery experimentally in pigs and to monitor the development of important immunoregulatory cytokines in blood collected at various stages of the disease. Methods Ten conventional pigs (~23 kg were orally inoculated with Brachyspira hyodysenteriae B204T. Eight animals developed muco-haemorrhagic diarrhoea with impaired general body condition. Blood was sampled before inoculation and repeatedly during acute dysentery and recovery periods and cytokine levels of IL-1β, IL-6, Il-10, TNF-α and IFN-γ were measured by ELISA. Results IL-1β was increased at the beginning of the dysentery period and coincided with the appearance of Serum amyloid A and clinical signs of disease. TNF-α increased in all animals after inoculation, with a peak during dysentery, and IL-6 was found in 3 animals during dysentery and in the 2 animals that did not develop clinical signs of disease. IL-10 was found in all sick animals during the recovery period. IFN-γ was not detected on any occasion. Conclusion B. hyodysenteriae inoculation induced production of systemic levels of IL-1β during the dysentery period and increased levels of IL-10 coincided with recovery from dysentery.

  18. Analysis of IL-6, IL-10 and NF-κB Gene Polymorphisms in Aggressive and Chronic Periodontitis.

    Science.gov (United States)

    Toker, Hülya; Görgün, Emine Pirim; Korkmaz, Ertan Mahir

    2017-06-01

    Pro-inflammatory cytokines, interleukin-6 (IL-6), demonstrated to be suppressed by interleukin-10 (IL-10) are known to be regulated by the transcription factor nuclear factor-κB(NF-κB). The aim of this study was to ascertain the association between genetic polymorphism of these genes (IL-6(-174), IL-10(-597) and NF-κB1-94ins/del)) and chronic/aggressive periodontitis. Forty-five patients with chronic periodontitis (CP), 58 patients with aggressive periodontitis (AP) and 38 periodontally healthy subjects were included in this study. Genomic DNA was isolated from whole blood samples. The NF-κB, IL-6, and IL-10 polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Among subjects for the ins/ins genotypes of NF-κB1 gene, the AA genotypes of IL-10 presented a higher frequency in chronic periodontitis group than in healthy controls (p=0.023). A statistically significant difference in genotyping frequencies between AP group and healthy controls was observed for the IL-6 gene. The AA genotype of IL-10 was overrepresented in CP and AP groups compared to healthy controls (OR=9.93, 95% CI: 2.11-46.7, OR=5.7, 95% CI: 1.22-26.89, respectively). Within the limits of this study, it can be concluded that the IL-10 (-597) AA genotype is associated with susceptibility to chronic/aggressive periodontitis and IL-6 (-174) GG genotypes and G allele seems to be associated with aggressive periodontitis. Clinical relevance: The results of the current study indicate that IL-6 and IL-10 genotypes seem to be associated with aggressive periodontitis. Also, the AA genotypes of IL-10 presented a higher frequency in chronic periodontitis subjects with carrying NF-κB1 ins/ins genotypes. Copyright© by the National Institute of Public Health, Prague 2017

  19. The lysine deacetylase inhibitor Givinostat inhibits β-cell IL-1β induced IL-1β transcription and processing.

    Science.gov (United States)

    Dahllöf, Mattias S; Christensen, Dan P; Lundh, Morten; Dinarello, Charles A; Mascagni, Paolo; Grunnet, Lars G; Mandrup-Poulsen, Thomas

    2012-01-01

    Pro-inflammatory cytokines and chemokines, in particular IL-1β, IFNγ, and CXCL10, contribute to β-cell failure and loss in DM via IL-1R, IFNγR, and TLR4 signaling. IL-1 signaling deficiency reduces diabetes incidence, islet IL-1β secretion, and hyperglycemia in animal models of diabetes. Further, IL-1R antagonism improves normoglycemia and β-cell function in type 2 diabetic patients. Inhibition of lysine deacetylases (KDACi) counteracts β-cell toxicity induced by the combination of IL-1 and IFNγ and reduces diabetes incidence in non-obese diabetic (NOD) mice. We hypothesized that KDACi breaks an autoinflammatory circuit by differentially preventing β-cell expression of the β-cell toxic inflammatory molecules IL-1β and CXCL10 induced by single cytokines. CXCL10 did not induce transcription of IL-1β mRNA. IL-1β induced β-cell IL-1β mRNA and both IL-1β and IFNγ individually induced Cxcl10 mRNA transcription. Givinostat inhibited IL-1β-induced IL-1β mRNA expression in INS-1 and rat islets and IL-1β processing in INS-1 cells. Givinostat also reduced IFNγ induced Cxcl10 transcription in INS-1 cells but not in rat islets, while IL-1β induced Cxcl10 transcription was unaffected in both. INS-1 cells and rat islets of Langerhans were exposed to IL-1β, IFNγ or CXCL10 in the presence or absence of KDACi (givinostat). Cytokine and chemokine mRNA expressions were quantified by real-time qPCR, and IL-1β processing by western blotting of cell lysates. Inhibition of β-cell IL-1β expression and processing and Cxcl10 transcription contributes to the β-cell protective actions of KDACi. In vitro β-cell destructive effects of CXCL10 are not mediated via IL-1β transcription. The differential proinflammatory actions of KDACs may be attractive novel drug targets in DM.

  20. Autocrine role of vascular IL-15 in intimal thickening

    International Nuclear Information System (INIS)

    Cercek, Miha; Matsumoto, Michiaki; Li, Hongyan; Chyu, K.-Y.; Peter, Ashok; Shah, Prediman K.; Dimayuga, Paul C.

    2006-01-01

    Interleukin 15 (IL-15) is a pro-inflammatory cytokine that modulates T cell recruitment and activation, independent of antigen. It has been detected in human atherosclerotic plaques and atherosclerotic plaques of apoE-/- mice. IL-15 regulates fractalkine (FKN)-CX3CR1 chemokine signaling which is involved in atherogenesis and promotes SMC proliferation. We investigated the role of IL-15 in intimal thickening after arterial injury. Treatment of serum-stimulated SMC with IL-15 in vitro attenuated proliferation and suppressed CX3CR1 and FKN mRNA expression. The role of endogenous IL-15 in vivo was investigated in injured carotid arteries of mice. Periadventitial arterial injury resulted in increased IL-15 expression in the media and neointima, paralleled by increased IL-15 receptor α expression. Blockade of endogenous IL-15 increased intimal thickening. FKN and CX3CR1 expression increased after injury and were further augmented after IL-15 blockade. These data suggest that endogenous IL-15 attenuated intimal thickening after arterial injury. The potential mechanism of action is suppression of CX3CR1 signaling

  1. Role of IL-33 in inflammation and disease

    Directory of Open Access Journals (Sweden)

    Miller Ashley M

    2011-08-01

    Full Text Available Abstract Interleukin (IL-33 is a new member of the IL-1 superfamily of cytokines that is expressed by mainly stromal cells, such as epithelial and endothelial cells, and its expression is upregulated following pro-inflammatory stimulation. IL-33 can function both as a traditional cytokine and as a nuclear factor regulating gene transcription. It is thought to function as an 'alarmin' released following cell necrosis to alerting the immune system to tissue damage or stress. It mediates its biological effects via interaction with the receptors ST2 (IL-1RL1 and IL-1 receptor accessory protein (IL-1RAcP, both of which are widely expressed, particularly by innate immune cells and T helper 2 (Th2 cells. IL-33 strongly induces Th2 cytokine production from these cells and can promote the pathogenesis of Th2-related disease such as asthma, atopic dermatitis and anaphylaxis. However, IL-33 has shown various protective effects in cardiovascular diseases such as atherosclerosis, obesity, type 2 diabetes and cardiac remodeling. Thus, the effects of IL-33 are either pro- or anti-inflammatory depending on the disease and the model. In this review the role of IL-33 in the inflammation of several disease pathologies will be discussed, with particular emphasis on recent advances.

  2. Immunity to infection in IL-17-deficient mice and humans.

    Science.gov (United States)

    Cypowyj, Sophie; Picard, Capucine; Maródi, László; Casanova, Jean-Laurent; Puel, Anne

    2012-09-01

    Mice with defective IL-17 immunity display a broad vulnerability to various infectious agents at diverse mucocutaneous surfaces. In humans, the study of patients with various primary immunodeficiencies, including autosomal dominant hyper-IgE syndrome caused by dominant-negative STAT3 mutations and autosomal recessive autoimmune polyendocrinopathy syndrome type 1 caused by null mutations in AIRE, has suggested that IL-17A, IL-17F and/or IL-22 are essential for mucocutaneous immunity to Candida albicans. This hypothesis was confirmed by the identification of rare patients with chronic mucocutaneous candidiasis (CMC) due to autosomal recessive IL-17RA deficiency and autosomal dominant IL-17F deficiency. Heterozygosity for gain-of-function mutations in STAT1 in additional patients with CMC was recently shown to inhibit the development of IL-17 T cells. Although the infectious phenotype of patients with CMC and inborn errors of IL-17 immunity remains to be finely delineated, it appears that human IL-17A and IL-17F display redundancy for protective immunity in natural conditions that is not seen in their mouse orthologs in experimental conditions. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. A modular interface of IL-4 allows for scalable affinity without affecting specificity for the IL-4 receptor

    Directory of Open Access Journals (Sweden)

    Sebald Walter

    2006-04-01

    Full Text Available Abstract Background Interleukin 4 (IL-4 is a key regulator of the immune system and an important factor in the development of allergic hypersensitivity. Together with interleukin 13 (IL-13, IL-4 plays an important role in exacerbating allergic and asthmatic symptoms. For signal transduction, both cytokines can utilise the same receptor, consisting of the IL-4Rα and the IL-13Rα1 chain, offering an explanation for their overlapping biological functions. Since both cytokine ligands share only moderate similarity on the amino acid sequence level, molecular recognition of the ligands by both receptor subunits is of great interest. IL-4 and IL-13 are interesting targets for allergy and asthma therapies. Knowledge of the binding mechanism will be important for the generation of either IL-4 or IL-13 specific drugs. Results We present a structure/function analysis of the IL-4 ligand-receptor interaction. Structural determination of a number of IL-4 variants together with in vitro binding studies show that IL-4 and its high-affinity receptor subunit IL-4Rα interact via a modular protein-protein interface consisting of three independently-acting interaction clusters. For high-affinity binding of wild-type IL-4 to its receptor IL-4Rα, only two of these clusters (i.e. cluster 1 centered around Glu9 and cluster 2 around Arg88 contribute significantly to the free binding energy. Mutating residues Thr13 or Phe82 located in cluster 3 to aspartate results in super-agonistic IL-4 variants. All three clusters are fully engaged in these variants, generating a three-fold higher binding affinity for IL-4Rα. Mutagenesis studies reveal that IL-13 utilizes the same main binding determinants, i.e. Glu11 (cluster 1 and Arg64 (cluster 2, suggesting that IL-13 also uses this modular protein interface architecture. Conclusion The modular architecture of the IL-4-IL-4Rα interface suggests a possible mechanism by which proteins might be able to generate binding affinity

  4. The effects of IL-17 upon human natural killer cells.

    Science.gov (United States)

    Al Omar, Suliman; Flanagan, Brian F; Almehmadi, Mazen; Christmas, Stephen E

    2013-04-01

    These experiments were designed to investigate the effects of IL-17 upon the phenotype and function of human Natural Killer (NK) cells. Peripheral blood mononuclear cells from healthy subjects were cultured in the presence or absence of different combinations of IL-17s and changes in relative numbers and cell surface phenotype of NK cells and CD56+CD3+ cells measured by flow cytometry. Real time PCR was used to measure changes in expression of the cytotoxicity-related genes perforin A and granzymes A and B and IL-17 receptors. A chromium release assay was used to measure cytotoxic function against K562 tumour cells. IL-17D, IL-17A, IL-17F or the combination of both of the latter had little effect upon NK cell surface expression of Killer Immunoglobulin-like Receptors, although IL-17A modestly increased NK cell numbers. Slight but not significant increases in expression of perforin and granzymes were induced by IL-17A and/or IL-17F. Both IL-17A and D significantly increased cytotoxic function of NK cells at some E:T ratios. Similarly, numbers of NK cells induced to express CD107a after interaction with K562 cells were increased, but not significantly, by all combinations of IL-17s tested. IL-17RC was not found at the NK cell surface but was expressed at the message level and the protein detected intracellularly. NK cells are known to produce IL-17 but here we report that there is little response to this cytokine although some isoforms may moderately enhance cytotoxic function. There may therefore be some enhancement of NK cell function resulting from Th17 cell activation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Genetic variation in IL-1β, IL-2, IL-6, TSPO and BDNF and response to duloxetine or placebo treatment in major depressive disorder.

    Science.gov (United States)

    Maciukiewicz, Malgorzata; Marshe, Victoria S; Tiwari, Arun K; Fonseka, Trehani M; Freeman, Natalie; Rotzinger, Susan; Foster, Jane A; Kennedy, James L; Kennedy, Sidney H; Müller, Daniel J

    2015-11-01

    This study investigated polymorphisms of five inflammatory-related genes for association with duloxetine and placebo response in patients with major depression. Twenty SNPs in IL-1β, IL-2, IL-6, TSPO and BDNF were genotyped in major depressive disorder patients treated with either duloxetine (n = 215) or placebo (n = 235) for up to 8 weeks. Treatment response was measured with the Montgomery-Åsberg Depression Rating Scale. IL-6 variants rs2066992 and rs10242595 were nominally associated with response to duloxetine (p = 0.047 and p = 0.028, respectively). Notably, the variant rs2066992 was also associated with placebo response (p = 0.026). However, none of our results remained significant after correction for multiple testing. Our findings tentatively suggest that IL-6 variants play a role in duloxetine and placebo response, which warrants further investigation.

  6. Il disegno gotico di San Giovanni Valdarno

    Directory of Open Access Journals (Sweden)

    Maria Teresa Bartoli

    2017-12-01

    Full Text Available San Giovanni Valdarno è una città del Valdarno di Sopra, il cui attuale centro storico fu la prima delle terre nuove della Repubblica Fiorentina, fondata alla fine del XIII secolo. Le vicende storiche della trasformazione del nucleo murato originario sono state oggetto di molti studi, ma la logica del suo particolare disegno non è stata molto investigata. L’approccio archeologico è quindi giustificato dal fatto che, per ciò che riguarda la forma del progetto urbano originario, gli studi finora pubblicati non vanno molto oltre la definizione di «progettazione ortogonale», data da David Friedman, suo maggiore studioso. I giudizi su di essa si sono quindi attestati sulla generica attribuzione di virtù e difetti che la tradizione storiografica annette alla città medievale, applicando formule basate su paradigmi convenzionali.Volendo condurre la ricerca di una descrizione significativa del tessuto materiale della città attingendo a paradigmi appartenenti al momento della sua realizzazione, è stato condotto uno studio metrico sulla forma della città storica, con riferimento al sistema del braccio fiorentino, considerato come parametro di riferimento fondamentale per la comprensione di un manufatto di dimensione urbana. L’aspetto archeologico della ricerca consiste quindi nella ricostruzione complessa di un paradigma dimenticato dall’attuale tradizione storiografica, alla luce del quale emergono negli oggetti storici significati e valori caduti dalla memoria trasmessa.L’analisi, condotta sulla planimetria digitale con il supporto di documenti storici del ‘200 e del ‘500, ha fatto emergere l’ordine logico e continuo del disegno geometrico della città fondata, replicabile a mente (e perciò memorabile, messo in opera nella pianta urbana, rendendo esplicita la sua logica e le sue connessioni sia con la cultura scientifica del tempo, sia con la tradizione storica precedente, risalendo a Vitruvio. Ai fini di interpretare

  7. International space Launch Services Today, ILS

    Science.gov (United States)

    Rymarcsuk, James A.; Haase, Ethan E.

    2002-01-01

    In the last five years the international space launch industry has undergone substantial change. New entrants and existing players in this market have introduced new and upgraded vehicles with greater lift capability than was available five years ago. In addition, some of these vehicles offer reduced risk from their predecessors thanks to design improvements and reductions in the number of failure points. The entry of these vehicles have generated greater supply, increased choice, and improved capabilities to the benefit of satellite operators and manufacturers. Some launch service providers have also enhanced the products and services they offer due to the increased competitiveness in the market. Although the number of commercial satellites launched per year has remained within a fairly narrow range in the last five years, expectations for the future that were once very optimistic have fallen dramatically. The significant number of commercial NGSO satellites launched in the late 1990s helped raise these expectations, but today, the predicted continued growth in launches due to NGSO and broadband systems has not materialized. Despite the decline in expectations from the late 1990s, however, the satellite market that the launch industry supports remains robust. Satellite operators maintain generally favorable financial positions, but the number of satellites required to provide services worldwide is growing slowly, with the number of new and replacement satellites launched per year remaining essentially flat. Satellite operators are undergoing consolidation that is rendering them stronger than ever, and putting them in a position to demand better service from their launch service providers. The increase in supply in the marketplace and the corresponding lack of growth in demand has led to a highly competitive marketplace for launch services internationally. ILS is well positioned with products and services to meet customer needs. Key customer buying factors include

  8. Prolonged restraint stress increases IL-6, reduces IL-10, and causes persistent depressive-like behavior that is reversed by recombinant IL-10.

    Directory of Open Access Journals (Sweden)

    Jeffrey L Voorhees

    Full Text Available Altered inflammatory cytokine profiles are often observed in individuals suffering from major depression. Recent clinical work reports on elevated IL-6 and decreased IL-10 in depression. Elevated IL-6 has served as a consistent biomarker of depression and IL-10 is proposed to influence depressive behavior through its ability to counterbalance pro-inflammatory cytokine expression. Clinical and animal studies suggest a role for IL-10 in modifying depressive behavior. Murine restraint stress (RST is regularly employed in the study of behavioral and biological symptoms associated with depressive disorders. While responses to acute RST exposure have been widely characterized, few studies have examined the ongoing and longitudinal effects of extended RST and fewer still have examined the lasting impact during the post-stress period. Consistent with clinical data, we report that a protocol of prolonged murine RST produced altered cytokine profiles similar to those observed in major depressive disorder. Parallel to these changes in circulating cytokines, IL-10 mRNA expression was diminished in the cortex and hippocampus throughout the stress period and following cessation of RST. Moreover, chronic RST promoted depressive-like behavior throughout the 28-day stress period and these depressive-like complications were maintained weeks after cessation of RST. Because of the correlation between IL-10 suppression and depressive behavior and because many successful antidepressant therapies yield increases in IL-10, we examined the effects of IL-10 treatment on RST-induced behavioral changes. Behavioral deficits induced by RST were reversed by exogenous administration of recombinant IL-10. This work provides one of the first reports describing the biological and behavioral impact following prolonged RST and, taken together, this study provides details on the correlation between responses to chronic RST and those seen in depressive disorders.

  9. Blocking IL-17A Alleviates Diabetic Retinopathy in Rodents

    Directory of Open Access Journals (Sweden)

    Ao-Wang Qiu

    2017-02-01

    Full Text Available Background/Aims: Interleukin (IL-17A, a proinflammatory cytokine, has been implicated in several autoimmune diseases. However, it is unclear whether IL-17A is involved in diabetic retinopathy (DR, one of the most serious complications of autoimmune diabetes. This study aimed to demonstrate that IL-17A exacerbates DR by affecting retinal Müller cell function. Methods: High glucose (HG-treated rat Müller cell line (rMC-1 was exposed to IL-17A, anti-IL-17A-neutralizing monoclonal antibody (mAb or/and anti-IL-17 receptor (RA-neutralizing mAb for 24 h. For in vivo study, DR was induced by intraperitoneal injections of streptozotocin (STZ. DR model mice were treated with anti-IL-17A mAb or anti-IL-17RA mAb in the vitreous cavity. Mice that were prepared for retinal angiography were sacrificed two weeks after intravitreal injection, while the rest were sacrificed two days after intravitreal injection. Results: IL-17A production and IL-17RA expression were increased in both HG-treated rMC-1 and DR retina. HG induced rMC-1 activation and dysfunction, as determined by the increased GFAP, VEGF and glutamate levels as well as the downregulated GS and EAAT1 expression. IL-17A exacerbated the HG-induced rMC-1 functional disorders, whereas either anti-IL-17A mAb or anti-IL-17RA mAb alleviated the HG-induced rMC-1 disorders. Intravitreal injections with anti-IL-17A mAb or anti-IL-17RA mAb in DR model mice reduced Müller cell dysfunction, vascular leukostasis, vascular leakage, tight junction protein downregulation and ganglion cell apoptosis in the retina. Conclusions: IL-17A aggravates DR-like pathology at least partly by impairing retinal Müller cell function. Blocking IL-17A is a potential therapeutic strategy for DR.

  10. Blocking IL-17A Alleviates Diabetic Retinopathy in Rodents.

    Science.gov (United States)

    Qiu, Ao-Wang; Liu, Qing-Huai; Wang, Jun-Ling

    2017-01-01

    Interleukin (IL)-17A, a proinflammatory cytokine, has been implicated in several autoimmune diseases. However, it is unclear whether IL-17A is involved in diabetic retinopathy (DR), one of the most serious complications of autoimmune diabetes. This study aimed to demonstrate that IL-17A exacerbates DR by affecting retinal Müller cell function. High glucose (HG)-treated rat Müller cell line (rMC-1) was exposed to IL-17A, anti-IL-17A-neutralizing monoclonal antibody (mAb) or/and anti-IL-17 receptor (R)A-neutralizing mAb for 24 h. For in vivo study, DR was induced by intraperitoneal injections of streptozotocin (STZ). DR model mice were treated with anti-IL-17A mAb or anti-IL-17RA mAb in the vitreous cavity. Mice that were prepared for retinal angiography were sacrificed two weeks after intravitreal injection, while the rest were sacrificed two days after intravitreal injection. IL-17A production and IL-17RA expression were increased in both HG-treated rMC-1 and DR retina. HG induced rMC-1 activation and dysfunction, as determined by the increased GFAP, VEGF and glutamate levels as well as the downregulated GS and EAAT1 expression. IL-17A exacerbated the HG-induced rMC-1 functional disorders, whereas either anti-IL-17A mAb or anti-IL-17RA mAb alleviated the HG-induced rMC-1 disorders. Intravitreal injections with anti-IL-17A mAb or anti-IL-17RA mAb in DR model mice reduced Müller cell dysfunction, vascular leukostasis, vascular leakage, tight junction protein downregulation and ganglion cell apoptosis in the retina. IL-17A aggravates DR-like pathology at least partly by impairing retinal Müller cell function. Blocking IL-17A is a potential therapeutic strategy for DR. © 2017 The Author(s)Published by S. Karger AG, Basel.

  11. Myxoma virus expressing a fusion protein of interleukin-15 (IL15 and IL15 receptor alpha has enhanced antitumor activity.

    Directory of Open Access Journals (Sweden)

    Vesna Tosic

    Full Text Available Myxoma virus, a rabbit poxvirus, can efficiently infect various types of mouse and human cancer cells. It is a strict rabbit-specific pathogen, and is thought to be safe as a therapeutic agent in all non-rabbit hosts tested including mice and humans. Interleukin-15 (IL15 is an immuno-modulatory cytokine with significant potential for stimulating anti-tumor T lymphocytes and NK cells. Co-expression of IL15 with the α subunit of IL15 receptor (IL15Rα greatly enhances IL15 stability and bioavailability. Therefore, we engineered a new recombinant myxoma virus (vMyx-IL15Rα-tdTr, which expresses an IL15Rα-IL15 fusion protein plus tdTomato red fluorescent reporter protein. Permissive rabbit kidney epithelial (RK-13 cells infected with vMyx-IL15Rα-tdTr expressed and secreted the IL15Rα-IL15 fusion protein. Functional activity was confirmed by demonstrating that the secreted fusion protein stimulated proliferation of cytokine-dependent CTLL-2 cells. Multi-step growth curves showed that murine melanoma (B16-F10 and B16.SIY cell lines were permissive to vMyx-IL15Rα-tdTr infection. In vivo experiments in RAG1-/- mice showed that subcutaneous B16-F10 tumors treated with vMyx-IL15Rα-tdTr exhibited attenuated tumor growth and a significant survival benefit for the treated group compared to the PBS control and the control viruses (vMyx-IL15-tdTr and vMyx-tdTr. Immunohistological analysis of the subcutaneous tumors showed dramatically increased infiltration of NK cells in vMyx-IL15Rα-tdTr treated tumors compared to the controls. In vivo experiments with immunocompetent C57BL/6 mice revealed a strong infiltrate of both NK cells and CD8+ T cells in response to vMyx-IL15Rα-tdTr, and prolonged survival. We conclude that delivery of IL15Rα-IL15 in a myxoma virus vector stimulates both innate and adaptive components of the immune system.

  12. E1A expression dysregulates IL-8 production and suppresses IL-6 production by lung epithelial cells

    Directory of Open Access Journals (Sweden)

    Snoek Mieke

    2005-09-01

    Full Text Available Abstract Background The adenoviral protein E1A has been proposed to play a role in the pathophysiology of COPD, in particular by increasing IL-8 gene transcription of lung epithelial cells in response to cigarette smoke-constituents such as LPS. As IL-8 production is also under tight post-transcriptional control, we planned to study whether E1A affected IL-8 production post-transcriptionally. The production of IL-6 by E1A-positive cells had not been addressed and was studied in parallel. Based on our previous work into the regulation of IL-8 and IL-6 production in airway epithelial cells, we used the lung epithelial-like cell line NCI-H292 to generate stable transfectants expressing either E1A and/or E1B, which is known to frequently co-integrate with E1A. We analyzed IL-8 and IL-6 production and the underlying regulatory processes in response to LPS and TNF-α. Methods Stable transfectants were generated and characterized with immunohistochemistry, western blot and flow cytometry. IL-8 and IL-6 protein production was measured by ELISA. Levels of IL-8 and IL-6 mRNA were measured using specific radiolabeled probes. EMSA was used to assess transcriptional activation of relevant transcription factors. Post-transcriptional regulation of mRNA half-life was measured by Actinomycin D chase experiments. Results Most of the sixteen E1A-expressing transfectants showed suppression of IL-6 production, indicative of biologically active E1A. Significant but no uniform effects on IL-8 production, nor on transcriptional and post-transcriptional regulation of IL-8 production, were observed in the panel of E1A-expressing transfectants. E1B expression exerted similar effects as E1A on IL-8 production. Conclusion Our results indicate that integration of adenoviral DNA and expression of E1A and E1B can either increase or decrease IL-8 production. Furthermore, we conclude that expression of E1A suppresses IL-6 production. These findings question the unique role of E1

  13. Il "rex sacrorum" in Africa: testimonianze

    Directory of Open Access Journals (Sweden)

    Chantal GABRIELLI

    2010-02-01

    Full Text Available RESUMEN: Questo articolo analizza alcune epigrafi provenienti da due province romane dell'Africa (Mauretania Caesariensis e Numidia, che presentano la carica di rex sacrorum. Tale sacerdozio, creato a Roma nei primi secoli délia repubblica è presente nel contesto africano in época imperiale con una valenza precisa: il termine rex sacrorum sembra essere la traduzione in latino di una carica religiosa púnica e indicherebbe forse un'autorità religiosa locale.ABSTRACT: This paper analyses some inscriptions from two Roman provinces of Africa (Mauretania Caesariensis and Numidia, which have the title rex sacrorum. This priesthood, created at the start of the Republic, appears in the African context in the imperial age with a further value; the rex sacrorum seems to be the translation in Latin of a Neo-Punic word, that is a native priesthood, perhaps a chief religious authority.

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

    International Nuclear Information System (INIS)

    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)

  15. Study on the aqueous humor contents of IL-1β and IL-6 in rabbits after extracapsular extraction of lens

    International Nuclear Information System (INIS)

    Zhao Jun

    2007-01-01

    Objective: To explore the relationship between the development of posterior capsular opacification and the aqueous humor contents of IL-1β and IL-6 after extracapsular extraction of lens in rabbits. Methods: Extracapsular extraction of lens was performed in 30 New Zealand rabbits. Aqueous humor contents of IL-1β and IL-6 were repeatedly determined with RIA and ophthal-moscopic as well as slit-lamp examination were repeatedly performed to detect any posterior capsular opacification developed on dl, d3, 1w, 2w, 1 month, 3 month posteperatively. Results: The aqueous humor contents of IL-1β and IL-6 increased gradually after operation, reached the peak on d7-d14, then gradually returned to within normal range by 2nd or 3rd month. Beginning from one month post-operatively, posterior capsular opacification was observed in some rabbits. By the end of 3rd month, Grade I opacification was developed in 5 rabbits, Grade H in 9 rabbits with Grade III (fundus view obliterated) in 14 rabbits. Peak IL-1β and IL- 6 content values were positively correlated with grading of future opacification. Conclusion: IL-1β and IL-6 might play important roles in the development of posterior capsular opacification after lens extraction in rabbits. (authors)

  16. Combination of IL-6, IL-10, and MCP-1 with traditional serum tumor markers in lung cancer diagnosis and prognosis.

    Science.gov (United States)

    Pan, Y W; Zhou, Z G; Wang, M; Dong, J Q; Du, K P; Li, S; Liu, Y L; Lv, P J; Gao, J B

    2016-11-03

    Early detection and treatment is critically important for lung cancer patients. Inflammatory mediators such as IL-6, IL-10, and MCP-1 participate in lung cancer regulation. CEA, CA125, and ProGRP are commonly used serum tumor markers for lung cancer. In this study, we assessed the sensitivity and specificity of CEA, CA125, and ProGRP when used in combination with IL-6, IL-10, and MCP in lung cancer diagnosis. Serum from three different groups (healthy controls, individuals with high risk for lung cancer, and lung cancer patients) was collected. Electrochemiluminescence was used to detect expressions of CEA, CA125, and ProGRP; ELISA was used to examine serum levels of IL-6, IL-10, and MCP-1. Specificity and sensitivity of single as well as combination markers in lung cancer diagnosis were determined. Results indicated that CEA, CA125, ProGRP, and MCP-1 were significantly up-regulated in lung cancer patients as compared to those in controls and high risk individuals. Higher IL-6 and IL-10 levels were observed in both lung cancer patients and high-risk individuals as compared to those in controls. Highest sensitivity (95.2%) in cancer diagnosis was achieved when all six markers were used. This was followed by a combination of IL-6, IL-10, CEA, CA125, and ProGRP (92.6%). The most sensitive (88.6%). Four-marker combination was composed of IL-6, CEA, CA125, and ProGRP. As the combined usage of CEA, CA125, ProGRP, IL-6, IL-10, and MCP-1 significantly improved sensitivity of lung cancer detection; this biomarker arrangement may be beneficial for early diagnosis, treatment, and prognosis of lung cancer.

  17. Genetic variants in IL-6 and IL-10 genes and susceptibility to hepatocellular carcinoma in HCV infected patients.

    Science.gov (United States)

    Sghaier, Ikram; Mouelhi, Leila; Rabia, Noor A; Alsaleh, Bano R; Ghazoueni, Ezzedine; Almawi, Wassim Y; Loueslati, Besma Yacoubi

    2017-01-01

    Hepatitis C virus (HCV) infection is the major cause of hepatocellular carcinoma (HCC), a common primary liver malignancy, and the third leading cause of cancer-related death. The HCC risk increases with the severity of liver inflammation, and the clinical course of HCV infection depends on a balance between pro- and anti-inflammatory cytokines. The former includes interleukin (IL)-6, while the latter includes IL-10. However, the exact pathogenic mechanisms underlying IL-6 and IL-10 effects remain unclear. The present study evaluated 174 chronic HCV Tunisian patients. Polymorphisms of IL-6 (rs1880242, rs1474847, rs2069840, rs1800797, rs1800796, rs2069845, rs2069827, rs1474348, rs1800795), and IL-10 (rs1800896, rs1800871, rs1800872, rs1554286, rs1878672, rs1518111) were determined by real-time PCR. Notable differences between chronic HCV-infected patients and HCC patients were observed for the three IL-10 SNPs; rs1800871 (-819T/C), rs1800872 (-592A/C), and rs1878672. Carriage of IL-6 rs1800796 G/G genotype, IL-6 rs1474358 C-allele, and IL-6 rs1800797 A-allele was more frequent in chronic HCV-infected patients than in HCC patients. On the other hand, IL-6 rs1474358 GG genotype had a favourable factor for HCC establishment. IL-10 and IL-6 SNPs markedly influence the clinical outcomes of HCV infection. These SNPs could be used as biomarkers for early detection and molecular therapy for preventing HCC, and prognostic factors for predicting the clinical outcomes of HCC. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Determinants of IL-6 levels during HIV infection

    DEFF Research Database (Denmark)

    Borges, Alvaro H; O'Connor, Jemma L; Phillips, Andrew N

    2014-01-01

    INTRODUCTION: Elevated IL-6 levels have been linked to increased risk of cardiovascular disease (CVD), cancer and death. Compared to the general population, treated HIV+ persons have 50-100% higher IL-6 levels, but few data on the determinants of IL-6 levels during HIV infection currently exist....... MATERIAL AND METHODS: Participants in three international HIV trials (SMART, ESPRIT and SILCAAT) with IL-6 plasma levels measured at baseline were included (N=9864). Factors independently associated with log2-transformed IL-6 level were identified by multivariate linear regression; exponentiated estimates...... corresponding to fold differences (FDs) in IL-6 were calculated. Demographics (age, gender, race, BMI) and HIV-specific variables (nadir and entry CD4 counts, HIV-RNA, use of different ART regimens) were investigated in all three trials. In SMART (N=4498), smoking, comorbidities (CVD, diabetes, hepatitis B...

  19. Il dito di Galileo le dieci grandi idee della scienza

    CERN Document Server

    Atkins, Peter

    2004-01-01

    Domande e risposte per dieci idee che hanno plasmato il mondo di oggi. Possiamo rintracciare l'origine e il divenire del cosmo? Perché spazio e tempo formano una cosa sola? Che cosa significa l'evoluzione del vivente? Perché il DNA è così importante? Perché il mondo ha bisogno di energia? E com'è che l'aumento dell'entropia scandisce il cambiamento dell'intero universo? Cosa sono gli atomi e cosa c'è di più piccolo di essi? Perché la simmetria della natura e dell'arte cattura il nostro senso della bellezza? Cosa sono quegli elusivi quanti alla base della fisica contemporanea? Siamo sicuri che l'aritmetica non ci inganni? Peter Atkins offre una guida chiara e completa all'impresa scientifica, seguendo la via indicata dal dito di Galileo.

  20. Noi siamo quello che ricordiamo - Le frazze di Crucoli: il teatro, il rito, il riscatto sociale

    Directory of Open Access Journals (Sweden)

    Tonia Mingrone

    2012-01-01

    Full Text Available Abstract - IT Questo lavoro nasce da una ricerca di campo sulle frazze, termine dialettale che indica le farse di Carnevale che si rappresentavano fino a cinquant’anni fa in molti paesi calabresi, tra cui il mio, Crucoli, in provincia di Crotone. Lo scopo di questo lavoro non è fare un resoconto esaustivo di tutto ciò che accadeva a Crucoli durante la celebrazione del Carnevale, impresa assai difficile dal momento che non ci sono documenti scritti e quindi bisogna affidarsi ai racconti orali delle persone intervistate, spesso non fedeli alla realtà, perché modificati dal tempo e dalla memoria. L’approccio con cui ho intrapreso questa ricerca è sicuramente legato all’aspetto teatrale e performativo dell’evento, senza trascurarne la rilevanza antropologica. Il materiale raccolto è frutto di interviste e colloqui con la gente del posto unito ad un grande lavoro di ricerca bibliografica di autori che avevano trattato di questo argomento in relazione ai loro paesi di origine.Lo scopo è quello di delineare l’organizzazione e lo svolgimento delle frazze, cercando di ricostruire la sua durata e le ripercussioni sulla comunità, nonché dimostrare ancora una volta come il teatro, messo a disposizione di alcuni eventi, diventi un mezzo forte di liberazione e di contestazione. Abstract - FR Cet article prend sa naissance par une recherche sur champ concernant les frazze, terme dialectal qui dénote les farces du Carnaval mises en scène jusqu'à il y a cinquante ans dans plusieurs villages en Calabria, entre eux le mien, Crucoli, dans la province de Crotone. La raison de ce travail n'est pas d'accomplir un compte rendu exhaustif de tout ce qui avait lieu à Crucoli pendant la célébration du Carnaval, l'exploit étant très difficile, du moment qu'aucun document écrit a été parvenu et par conséquence il est nécessaire de se remettre aux contes des témoins interviewés, souvent pas fidèles au réel, parce-que détournés par les

  1. The role of IL-6 in neurodevelopment after prenatal stress.

    Science.gov (United States)

    Gumusoglu, Serena B; Fine, Rebecca S; Murray, Samuel J; Bittle, Jada L; Stevens, Hanna E

    2017-10-01

    Prenatal stress exposure is associated with adverse psychiatric outcomes, including autism and ADHD, as well as locomotor and social inhibition and anxiety-like behaviors in animal offspring. Similarly, maternal immune activation also contributes to psychiatric risk and aberrant offspring behavior. The mechanisms underlying these outcomes are not clear. Offspring microglia and the pro-inflammatory cytokine interleukin-6 (IL-6), known to influence microglia, may serve as common mechanisms between prenatal stress and prenatal immune activation. To evaluate the role of prenatal IL-6 in prenatal stress, microglia morphological analyses were conducted at embryonic days 14 (E14), E15, and in adult mice. Offspring microglia and behavior were evaluated after repetitive maternal restraint stress, repetitive maternal IL-6, or maternal IL-6 blockade during stress from E12 onwards. At E14, novel changes in cortical plate embryonic microglia were documented-a greater density of the mutivacuolated morphology. This resulted from either prenatal stress or IL-6 exposure and was prevented by IL-6 blockade during prenatal stress. Prenatal stress also resulted in increased microglia ramification in adult brain, as has been previously shown. As with embryonic microglia, prenatal IL-6 recapitulated prenatal stress-induced changes in adult microglia. Furthermore, prenatal IL-6 was able to recapitulate the delay in GABAergic progenitor migration caused by prenatal stress. However, IL-6 mechanisms were not necessary for this delay, which persisted after prenatal stress despite IL-6 blockade. As we have previously demonstrated, behavioral effects of prenatal stress in offspring, including increased anxiety-like behavior, decreased sociability, and locomotor inhibition, may be related to these GABAergic delays. While adult microglia changes were ameliorated by IL-6 blockade, these behavioral changes were independent of IL-6 mechanisms, similar to GABAergic delays. This and previous work from

  2. Il rischio tecnologico vantaggi e svantaggi del progresso scientifico

    CERN Document Server

    Lewis, H W

    1995-01-01

    I rischi della vita ; misurare il rischio ; la percezione del rischio ; la politica del rischio ; la valutazione del rischio ; la gestione del rischio ; il valore della vita ; qual è il livello "sufficiente" di sicurezza? ; incertezza, causalità, rilevabilità ; le delusioni della cautela ; sostanze chimiche tossiche ; sostanze chimiche cancerogene ; sicurezza sulle autostrade ; trasporto aereo ; radiazioni ionizzanti ; conbustibili fossili ; l'inverno nucleare ; radiazioni non ionizzanti ; quanto basta di statistica e di teoria delle probabilità ; epilogo : cosa significa tutto questo?.

  3. IL-26 Confers Proinflammatory Properties to Extracellular DNA.

    Science.gov (United States)

    Poli, Caroline; Augusto, Jean François; Dauvé, Jonathan; Adam, Clément; Preisser, Laurence; Larochette, Vincent; Pignon, Pascale; Savina, Ariel; Blanchard, Simon; Subra, Jean François; Chevailler, Alain; Procaccio, Vincent; Croué, Anne; Créminon, Christophe; Morel, Alain; Delneste, Yves; Fickenscher, Helmut; Jeannin, Pascale

    2017-05-01

    In physiological conditions, self-DNA released by dying cells is not detected by intracellular DNA sensors. In chronic inflammatory disorders, unabated inflammation has been associated with a break in innate immune tolerance to self-DNA. However, extracellular DNA has to complex with DNA-binding molecules to gain access to intracellular DNA sensors. IL-26 is a member of the IL-10 cytokine family, overexpressed in numerous chronic inflammatory diseases, in which biological activity remains unclear. We demonstrate in this study that IL-26 binds to genomic DNA, mitochondrial DNA, and neutrophil extracellular traps, and shuttles them in the cytosol of human myeloid cells. As a consequence, IL-26 allows extracellular DNA to trigger proinflammatory cytokine secretion by monocytes, in a STING- and inflammasome-dependent manner. Supporting these biological properties, IL-10-based modeling predicts two DNA-binding domains, two amphipathic helices, and an in-plane membrane anchor in IL-26, which are structural features of cationic amphipathic cell-penetrating peptides. In line with these properties, patients with active autoantibody-associated vasculitis, a chronic relapsing autoimmune inflammatory disease associated with extensive cell death, exhibit high levels of both circulating IL-26 and IL-26-DNA complexes. Moreover, in patients with crescentic glomerulonephritis, IL-26 is expressed by renal arterial smooth muscle cells and deposits in necrotizing lesions. Accordingly, human primary smooth cells secrete IL-26 in response to proinflammatory cytokines. In conclusion, IL-26 is a unique cationic protein more similar to a soluble pattern recognition receptor than to conventional cytokines. IL-26 expressed in inflammatory lesions confers proinflammatory properties to DNA released by dying cells, setting up a positive amplification loop between extensive cell death and unabated inflammation. Copyright © 2017 by The American Association of Immunologists, Inc.

  4. The role of IL-12 in experimental Trypanosoma cruzi infection

    Directory of Open Access Journals (Sweden)

    J.S. Silva

    1998-01-01

    Full Text Available Host resistance to Trypanosoma cruzi infection is dependent on both natural and acquired immune responses. During the early acute phase of infection in mice, natural killer (NK cell-derived IFN-g is involved in controlling intracellular parasite replication, mainly through the induction of nitric oxide biosynthesis by activated macrophages. We have shown that IL-12, a powerful inducer of IFN-g production by NK cells, is synthesized soon after trypomastigote-macrophage interaction. The role of IL-12 in the control of T. cruzi infection in vivo was determined by treating infected mice with anti-IL-12 monoclonal antibody (mAb and analyzing both parasitemia and mortality during the acute phase of infection. The anti-IL-12 mAb-treated mice had higher levels of parasitemia and mortality compared to control mice. Also, treatment of infected mice with mAb specific for IFN-g or TNF-a inhibited the protective effect of exogenous IL-12. On the other hand, TGF-ß and IL-10 produced by infected macrophages inhibited the induction and effects of IL-12. Therefore, while IL-12, TNF-a and IFN-g correlate with resistance to T. cruzi infection, TGF-ß and IL-10 promote susceptibility. These results provide support for a role of innate immunity in the control of T. cruzi infection. In addition to its protective role, IL-12 may also be involved in the modulation of T. cruzi-induced myocarditis, since treatment of infected mice with IL-12 or anti-IL-12 mAb leads to an enhanced or decreased inflammatory infiltrate in the heart, respectively. Understanding the role of the cytokines produced during the acute phase of T. cruzi infection and their involvement in protection and pathogenesis would be essential to devise new vaccines or therapies.

  5. Cellular sources of IL-17 in psoriasis: a paradigm shift?

    Science.gov (United States)

    Keijsers, Romy R M C; Joosten, Irma; van Erp, Piet E J; Koenen, Hans J P M; van de Kerkhof, Peter C M

    2014-11-01

    Psoriasis is a common chronic inflammatory skin disease that results from interplay between the immune system and the epithelium. In the light of very successful anticytokine therapies for psoriasis, the focus has been directed towards the adaptive immune system. Expression studies, genetic studies and treatments specifically targeting players of the IL-23/IL-17 pathway, point at an important role for IL-17 in the pathogenesis of psoriasis. IL-17 stimulates the keratinocytes to produce psoriasis-associated molecules, eventually leading to chronic skin inflammation. The current opinion is that IL-17 is mainly produced by T cells, so-called T-helper 17 (Th17) cells, in psoriasis. However, evidence is accumulating that cells of the innate immune system, like neutrophils, mast cells, γδ T cells and innate lymphoid cells are the main source of IL-17 in psoriasis, rather than T cells. The paradigm in this field of research is shifting. With this viewpoint article, we will address this novel concept by critically summarizing the current literature on this subject. In psoriatic arthritis and atherosclerosis, important conditions related to psoriasis, it was also found that the majority of IL-17 is associated with cells of the innate immune system. This new concept changes our view of IL-17. Blocking IL-17 with targeted treatments might be more far-reaching than previously thought; not only IL-17 production by T cells but also by innate immune cells is blocked. Furthermore, therapies specifically targeting IL-17 may not only improve psoriasis, but also comorbidity that is associated with the IL-17 pathway, hereby preventing serious complications on the long term. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Factors application of MW-mile method and participation in the allocation of charges by the drills use in electricity markets; Aplicacion de los factores de participacion y del metodo de MW-milla en la asignacion de cargos por uso de redes de transmision en mercados de electricidad

    Energy Technology Data Exchange (ETDEWEB)

    Alba-Gomez, L; Tovar-Hernandez, J. H; Gutierrez-Alcaraz, G [Instituto Tecnologico de Morelia, Michoacan (Mexico)]. E-mail: horaciotovar@mexico.com; ggutier@itmorelia.edu.mx

    2007-04-15

    Use of network allocation costs by shift factors and MW-Mile method is reported in this paper. Conventional shift factors are computed based on DC power flow. DC power flow requires to selecting a slack bus in order to avoid matrix singularity. Therefore, shift factors are slack bus dependent. In order to evade slack bus dependency, two approaches are considered. [Spanish] Este trabajo presenta la asignacion de costos por uso de red mediante la aplicacion de Factores de Participacion (FP) y el metodo de MW-Milla. Los FP clasicos son calculados a partir del modelo lineal de flujos de potencia para lo que se requiere de establecer un nodo de referencia a fin de eliminar la singularidad de la matriz de coeficientes. Por lo tanto, los FP son dependientes de la asignacion del nodo de referencia. Dos metodos alternativos para evitar la dependencia del nodo compensador en la obtencion de los factores de participacion son presentados.

  7. Structure and Mechanism of Receptoe Sharing by the IL-10R2 Common Chain

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Sung-il; Jones, Brandi C.; Logsdon, Naomi J.; Harris, Bethany D.; Deshpande, Ashlesha; Radaeva, Svetlana; Halloran, Brian A.; Gao, Bin; Walter, Mark R. (NIH); (UAB)

    2010-06-14

    IL-10R2 is a shared cell surface receptor required for the activation of five class 2 cytokines (IL-10, IL-22, IL-26, IL-28, and IL-29) that play critical roles in host defense. To define the molecular mechanisms that regulate its promiscuous binding, we have determined the crystal structure of the IL-10R2 ectodomain at 2.14 {angstrom} resolution. IL-10R2 residues required for binding were identified by alanine scanning and used to derive computational models of IL-10/IL-10R1/IL-10R2 and IL-22/IL-22R1/IL-10R2 ternary complexes. The models reveal a conserved binding epitope that is surrounded by two clefts that accommodate the structural and chemical diversity of the cytokines. These results provide a structural framework for interpreting IL-10R2 single nucleotide polymorphisms associated with human disease.

  8. Structure and Mechanism of Receptor Sharing by the IL-10R2 Common Chain

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Sung-il; Jones, Brandi C.; Logsdon, Naomi J.; Harris, Bethany D.; Deshpande, Ashlesha; Radaeva, Svetlana; Halloran, Brian A.; Gao, Bin; Walter, Mark R. (NIH); (UAB)

    2010-07-19

    IL-10R2 is a shared cell surface receptor required for the activation of five class 2 cytokines (IL-10, IL-22, IL-26, IL-28, and IL-29) that play critical roles in host defense. To define the molecular mechanisms that regulate its promiscuous binding, we have determined the crystal structure of the IL-10R2 ectodomain at 2.14 {angstrom} resolution. IL-10R2 residues required for binding were identified by alanine scanning and used to derive computational models of IL-10/IL-10R1/IL-10R2 and IL-22/IL-22R1/IL-10R2 ternary complexes. The models reveal a conserved binding epitope that is surrounded by two clefts that accommodate the structural and chemical diversity of the cytokines. These results provide a structural framework for interpreting IL-10R2 single nucleotide polymorphisms associated with human disease.

  9. Le développement durable : est-il possible? est-il mesurable?

    Directory of Open Access Journals (Sweden)

    Belmokaddem MOSTEFA

    2011-04-01

    Full Text Available A la première question, nous répondrons bien sûr, par l’affirmative puisque tous les pays sont engagés dans une nouvelle approche du développement qui ne consiste pas seulement à produire le plus de biens et au moindre coût, afin de vendre beaucoup et réaliser de grands profits. C’était la vision en vigueur dans toutes les techniques de gestion mais on s’est rendu compte que cette production, supposée au moindre coût, était en fait, souvent d’un coût exorbitant, relativement aux dégâts occasionnés dans l’environnement et dans les nuisances occasionnées à la santé de l’homme et à sa tranquillité. Il est temps d’inclure d’autres variables dans le calcul du prix de revient tout en revoyant certaines techniques de production trop salissantes, dangereuses ou grosses consommatrices d’énergie. Nous répondrons aussi par la négative quand on pense qu’au niveau micro économique, les comportements sont édictés par les satisfactions immédiates et les maximisations des profits. Ces comportements qui ne s’intéressent qu’aux résultats à court terme, ne s’intègrent pas facilement dans les plans de développement visant les équilibres macro économiques à long terme.A la deuxième question, nous dirons qu’il y a effectivement des indicateurs pour tester les niveaux de qualité dans l’éducation, la santé, les ressources naturelles... et les gains tirés au niveau social mais les calculs économiques qui déterminent la rentabilité des projets, les profits espérés, les risques financiers encourus ne sont pas toujours en rapport avec les efforts pour réaliser le développement durable qui, eux dépassent la simple notion d’efficacité et de satisfaction. Quand on pense aux générations futures, ce n’est pas seulement en termes de durée dans le temps mais aussi dans la manière d’apprécier les gains espérés.Notre recherche repose sur ces questions qui minent bien des efforts alors qu’il

  10. Autophagy is required for IL-2-mediated fibroblast growth

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Rui [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219 (United States); Tang, Daolin, E-mail: tangd2@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219 (United States); Lotze, Michael T., E-mail: lotzemt@upcm.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219 (United States); Zeh III, Herbert J., E-mail: zehh@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219 (United States)

    2013-02-15

    Autophagy is an evolutionarily conserved pathway responsible for delivery of cytoplasmic material into the lysosomal degradation pathway to enable vesicular exocytosis. Interleukin (IL)-2 is produced by T-cells and its activity is important for immunoregulation. Fibroblasts are an immune competent cell type, playing a critical role in wound healing, chronic inflammation, and tumor development. Although autophagy plays an important role in each of these processes, whether it regulates IL-2 activity in fibroblasts is unknown. Here, we show that autophagy is required for IL-2-induced cell growth in fibroblasts. IL-2 significantly induced autophagy in mouse embryonic fibroblasts (MEFs) and primary lung fibroblasts. Autophagy inhibitors (e.g., 3-methylamphetamine and bafilomycin A1) or knockdown of ATG5 and beclin 1 blocked clinical grade IL-2-induced autophagy. Moreover, IL-2 induced HMGB1 cytoplasmic translocation in MEFs and promoted interaction between HMGB1 and beclin1, which is required for autophagy induction. Pharmacological and genetic inhibition of autophagy inhibited IL-2-induced cell proliferation and enhanced IL-2-induced apoptosis. These findings suggest that autophagy is an important pro-survival regulator for IL-2-induced cell growth in fibroblasts.

  11. The role of IL-17 in vitiligo: A review.

    Science.gov (United States)

    Singh, Rasnik K; Lee, Kristina M; Vujkovic-Cvijin, Ivan; Ucmak, Derya; Farahnik, Benjamin; Abrouk, Michael; Nakamura, Mio; Zhu, Tian Hao; Bhutani, Tina; Wei, Maria; Liao, Wilson

    2016-04-01

    IL-17 is involved in the pathogenesis of several autoimmune diseases; however its role in vitiligo has not been well defined. Emerging human and mouse studies have demonstrated that systemic, tissue, and cellular levels of IL-17 are elevated in vitiligo. Many studies have also shown significant positive correlations between these levels and disease activity, extent, and severity. Treatments that improve vitiligo, such as ultraviolet B phototherapy, also modulate IL-17 levels. This review synthesizes our current understanding of how IL-17 may influence the pathogenesis of autoimmune vitiligo at the molecular level. This has implications for defining new vitiligo biomarkers and treatments. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Essential role of Stat6 in IL-4 signalling.

    Science.gov (United States)

    Takeda, K; Tanaka, T; Shi, W; Matsumoto, M; Minami, M; Kashiwamura, S; Nakanishi, K; Yoshida, N; Kishimoto, T; Akira, S

    1996-04-18

    Interleukin-4 (IL-4) is a pleiotropic lymphokine which plays an important role in the immune system. IL-4 activates two distinct signalling pathways through tyrosine phosphorylation of Stat6, a signal transducer and activator of transcription, and of a 170K protein called 4PS. To investigate the functional role of Stat6 in IL-4 signalling, we generated mice deficient in Stat6 by gene targeting. We report here that in the mutant mice, expression of CD23 and major histocompatibility complex (MHC) class II in resting B cells was not enhanced in response to IL-4. IL-4 induced B-cell proliferation costimulated by anti-IgM antibody was abolished. The T-cell proliferative response was also notably reduced. Furthermore, production of Th2 cytokines from T cells as well as IgE and IgG1 responses after nematode infection were profoundly reduced. These findings agreed with those obtained in IL-4 deficient mice or using antibodies to IL-4 and the IL-4 receptor. We conclude that Stat6 plays a central role in exerting IL-4 mediated biological responses.

  13. IL1B induced Smad 7 negatively regulates gastrin expression.

    Directory of Open Access Journals (Sweden)

    Dipanjana Datta De

    Full Text Available BACKGROUND: Helicobacter pylori elicited IL1B is one of the various modulators responsible for perturbation of acid secretion in gut. We have earlier reported that IL1B activated NFkB downregulates gastrin, a major modulator of acid secretion. However, we hypothesized that regulation of gastrin by IL1B would depend on the cell's ability to integrate inputs from multiple signaling pathways to generate appropriate biological response. PRINCIPAL FINDING: In this study, we report that IL1B induces Smad 7 expression by about 4.5 fold in gastric carcinoma cell line, AGS. Smad 7 resulted in transcriptional repression of gastrin promoter by about 6.5 fold when co-transfected with Smad 7 expression vector and gastrin-promoter luciferase in AGS cells. IL1B inhibited phosphorylation of Smad 3 and subsequently interfered with nuclear translocation of the positive Smad complex, thus occluding it off the gastrin promoter. IL1B promoter polymorphisms (-511T/-31C IL1B are known to be associated with H. pylori associated gastro-duodenal ulcer. We observed that IL1B expressed from -31T promoter driven IL1B cDNA elicited 3.5 fold more Smad 7 than that expressed from the IL1B-31C variant in AGS cells. This differential activation of Smad 7 by IL1B promoter variants translated into differential downregulation of gastrin expression. We further analyzed Smad 7, NFkB, IL1B and gastrin expression in antral gut biopsy samples of patients with H. pylori associated duodenal ulcer and normal individuals. We observed that individuals with duodenal ulcer had significantly lower levels of IL1B, Smad 7, NFkB and corresponding higher level of gastrin expression. CONCLUSION: Pro-inflammatory cytokine IL1B repress gastrin expression by activating Smad 7 and subsequent inhibition of nuclear localization of Smad 3/4 complex. Polymorphic promoter variants of IL1B gene can modulate the IL1B expression which resulted in differential activation Smad 7 and consequent repression of

  14. Targeting IL-2: an unexpected effect in treating immunological diseases.

    Science.gov (United States)

    Ye, Congxiu; Brand, David; Zheng, Song G

    2018-01-01

    Regulatory T cells (Treg) play a crucial role in maintaining immune homeostasis since Treg dysfunction in both animals and humans is associated with multi-organ autoimmune and inflammatory disease. While IL-2 is generally considered to promote T-cell proliferation and enhance effector T-cell function, recent studies have demonstrated that treatments that utilize low-dose IL-2 unexpectedly induce immune tolerance and promote Treg development resulting in the suppression of unwanted immune responses and eventually leading to treatment of some autoimmune disorders. In the present review, we discuss the biology of IL-2 and its signaling to help define the key role played by IL-2 in the development and function of Treg cells. We also summarize proof-of-concept clinical trials which have shown that low-dose IL-2 can control autoimmune diseases safely and effectively by specifically expanding and activating Treg. However, future studies will be needed to validate a better and safer dosing strategy for low-dose IL-2 treatments utilizing well-controlled clinical trials. More studies will also be needed to validate the appropriate dose of IL-2/anti-cytokine or IL-2/anti-IL-2 complex in the experimental animal models before moving to the clinic.

  15. IL-1 Receptor Antagonist Inhibits Early Granulation Formation.

    Science.gov (United States)

    Nicolli, Elizabeth A; Ghosh, Ankona; Haft, Sunny; Frank, Renee; Saunders, Cecil James; Cohen, Noam; Mirza, Natasha

    2016-04-01

    Using a functional model of airway granulation tissue in laryngotracheal stenosis, we investigated changes in histopathology and inflammatory markers within granulation tissue in response to an interleukin-1 receptor antagonist (IL-1Ra). This study allows us to further delineate the immune response to wound healing and potentially identify treatment markers. Laryngotracheal complexes (LTCs) of donor mice underwent direct airway injury. The LTCs were transplanted into subcutaneous tissue of recipient mice in 2 groups: IL-1Ra treated and untreated. The IL-1Ra-treated arm received daily intraperitoneal injections of IL-1Ra for 3 weeks. The LTCs were then harvested. Granulation formation was measured. The mRNA expression of transforming growth factor (TGF) beta and IL-1 was quantified using real-time reverse transcript polymerase chain reaction. There were statistically significant differences in lamina propria thickness. There were no statistically significant changes in mRNA expression of TGF-β and IL-1β between the treated and untreated specimens. Using a previously described murine model, we delineate inflammatory markers that can be targeted for potential therapy. While the levels of inflammatory markers do not change significantly, the lamina propria thickness shows that the effects of IL-1 have been inhibited. The early use of the IL-1Ra will inhibit the efficacy of IL-1 in the inflammatory cascade and can prevent early granulation formation. © The Author(s) 2015.

  16. M-Learning & e-inclusion. Il progetto ENSEMBLE

    Directory of Open Access Journals (Sweden)

    Maria Ranieri

    2013-03-01

    Full Text Available Nel corso degli ultimi dieci anni, l’Unione europea ha più volte sottolineato, nelle sue raccomandazioni e documenti, il ruolo che le ICT possono svolgere per favorire le opportunità di partecipazione ed integrazione dei cittadini più svantaggiati. In questo contesto, il progetto ENSEMBLE, qui presentato, si è proposto di mettere a punto una strategia d’impiego delle tecnologie della comunicazione per promuovere l’integrazione socio-culturale dei cittadini immigrati, facendo leva sull’uso di tecnologie come il lettore MP3 e il telefono cellulare, e sperimentando metodologie didattiche e formati comunicativi adatti agli strumenti impiegati.

  17. IL-12 Inhibits Lipopolysaccharide Stimulated Osteoclastogenesis in Mice

    Directory of Open Access Journals (Sweden)

    Masako Yoshimatsu

    2015-01-01

    Full Text Available Lipopolysaccharide (LPS is related to osteoclastogenesis in osteolytic diseases. Interleukin- (IL- 12 is an inflammatory cytokine that plays a critical role in host defense. In this study, we investigated the effects of IL-12 on LPS-induced osteoclastogenesis. LPS was administered with or without IL-12 into the supracalvariae of mice, and alterations in the calvarial suture were evaluated histochemically. The number of osteoclasts in the calvarial suture and the mRNA level of tartrate-resistant acid phosphatase (TRAP, an osteoclast marker, were lower in mice administered LPS with IL-12 than in mice administered LPS alone. The serum level of tartrate-resistant acid phosphatase 5b (TRACP 5b, a bone resorption marker, was also lower in mice administered LPS with IL-12 than in mice administered LPS alone. These results revealed that IL-12 might inhibit LPS-induced osteoclastogenesis and bone resorption. In TdT-mediated dUTP-biotin nick end-labeling (TUNEL assays, apoptotic changes in cells were recognized in the calvarial suture in mice administered LPS with IL-12. Furthermore, the mRNA levels of both Fas and FasL were increased in mice administered LPS with IL-12. Taken together, the findings demonstrate that LPS-induced osteoclastogenesis is inhibited by IL-12 and that this might arise through apoptotic changes in osteoclastogenesis-related cells induced by Fas/FasL interactions.

  18. Il desiderio Kitsch: i troppi paradisi di Walter Siti

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    Ornella Tajani

    2013-06-01

    Full Text Available Cosa ne è del desiderio all’interno del Kitsch, sistema in cui la vita è vissuta come uno spot pubblicitario e l’identità come una eterna performance? In una dimensione utopistica in cui l’uomo non cerca altro che una continua soddisfazione come possono trovare spazio le tensioni e le mancanze che muovono il desiderio? Dopo una premessa teorica su cosa è il Kitsch, l’intervento si propone di rispondere al quesito attraverso tre opere di Walter Siti: i romanzi Troppi paradisi e Autopsia dell’ossessione e il reportage narrativo Il canto del diavolo. In queste opere vengono individuati tre paradigmi dell’esperienza Kitsch: il turismo, la televisione e un certo tipo di prostituzione. Indagandone le modalità e analizzando le riflessioni dell’autore in merito si vedrà come si deforma il desiderio quando si trova a dover fare i conti con il perpetuo sforzo del Kitschmensch di camuffarsi, per dirla con Kundera, «dans le miroir du mensonge embellissant et de s’y reconnaître avec une satisfaction émue». La meravigliosa e sostenibilissima leggerezza dell’essere che assurge a cifra interpretativa dell’utopia Kitsch non prevede la presenza del desiderio se non nella sua veste di “realizzabilità”: il desiderio Kitsch, il surrogato del desiderio, è offerto in omaggio col prodotto che lo appaga.

  19. New insight to IL-23/IL-17 axis in Iranian infected adult patients with gastritis: effects of genes polymorphisms on expression of cytokines.

    Science.gov (United States)

    Shirzad, H; Bagheri, N; Azadegan-Dehkordi, F; Zamanzad, B; Izadpanah, E; Abdi, M; Ramazani, G; Sanei, M H; Ayoubian, H; Ahmadi, A; Jamalzehi, S; Aslani, P; Zandi, F

    2015-06-01

    Chronic inflammation is the hallmark of the pathogenesis of H. pylori-induced gastric cancer. IL-17A and IL-17F are inflammatory cytokines expressed by a novel subset of CD4+Th cells and play critical function in inflammation. We evaluated the relationship between IL-17A G197A, IL-17F A7488G and IL23R+2199 A/C polymorphisms with IL-6, IL-17, IL-21, IL-23 and TGF-β1 mRNAs expression in regard to H. pylori infection with chronic gastritis. Total RNA and genomic DNA were extracted from gastric biopsies of 58 H. pylori-infected patient with gastritis. Afterward, mucosal IL-6, IL-17, IL-21, IL-23 and TGF-β1 mRNAs expression and polymorphisms in IL-17A G197A, IL-17F A7488G and IL-23R +2199A/Cin gastric biopsies were determined by real-time PCR and PCR-RFLP. Our results show that IL-17A G197A, IL-17F A7488G andIL23R +2199A/C polymorphisms have no effect on mucosal expression of IL-6, IL-17, IL-21 and TGF-β1 mRNAs expression in H. pylori-infected patients with chronic gastritis. These results suggest that IL-17A G197A, IL-17F A7488G and IL23R +2199A/C polymorphisms no alter mucosal cytokine pattern in Iranian patients with H. pylori-associated gastritis diseases. © Acta Gastro-Enterologica Belgica.

  20. 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.

    Science.gov (United States)

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

    2014-09-05

    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 interactively via these cytokines to create a microenvironment that leads to the extension of ameloblastomas. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Structural basis for IL-1α recognition by a modified DNA aptamer that specifically inhibits IL-1α signaling

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Xiaoming; Gelinas, Amy D.; von Carlowitz, Ira; Janjic, Nebojsa; Pyle, Anna Marie (Yale); (SomaLogic)

    2017-10-09

    IL-1α is an essential cytokine that contributes to inflammatory responses and is implicated in various forms of pathogenesis and cancer. Here we report a naphthyl modified DNA aptamer that specifically binds IL-1α and inhibits its signaling pathway. By solving the crystal structure of the IL-1α/aptamer, we provide a high-resolution structure of this critical cytokine and we reveal its functional interaction interface with high-affinity ligands. The non-helical aptamer, which represents a highly compact nucleic acid structure, contains a wealth of new conformational features, including an unknown form of G-quadruplex. The IL-1α/aptamer interface is composed of unusual polar and hydrophobic elements, along with an elaborate hydrogen bonding network that is mediated by sodium ion. IL-1α uses the same interface to interact with both the aptamer and its cognate receptor IL-1RI, thereby suggesting a novel route to immunomodulatory therapeutics.

  2. Rappresentare e gestire patrimoni immobiliari: il BIM per il Facility Management

    Directory of Open Access Journals (Sweden)

    Massimiliano Lo Turco

    2015-12-01

    Full Text Available Il presente contributo intende esplorare le potenzialità delle metodologie di Building Information Modeling (BIM applicabili alle diverse fasi del processo edilizio, con specifico riferimento a linee guida e best practice di respiro internazionale che avvalorano flussi operativi virtuosi: la componente informativa, prevalentemente grafica in fase di progetto, si integra e si rinnova in formato prevalentemente alfanumerico, divenendo parte integrante dell’apparato gestionale e manutentivo dei manufatti. I casi studio sviluppati in collaborazione con il Servizio Edilizia e Logistica del Politecnico di Torino sostanziano tali procedure che, seppur ancora poco diffuse, traguardano obiettivi di interoperabilità: si illustrano approcci integrati di condivisione delle informazioni atti a definire una corretta programmazione degli interventi, applicabili dalla grande alla piccola scala, definendo strategie progettate per limitare l’attuazione di errate soluzioni.

  3. IL-2 and IL-15 dependent thymic development of Foxp3-expressing regulatory T lymphocytes.

    Science.gov (United States)

    Apert, Cécile; Romagnoli, Paola; van Meerwijk, Joost P M

    2018-04-01

    Immunosuppressive regulatory T lymphocytes (Treg) expressing the transcription factor Foxp3 play a vital role in the maintenance of tolerance of the immune-system to self and innocuous non-self. Most Treg that are critical for the maintenance of tolerance to self, develop as an independent T-cell lineage from common T cell precursors in the thymus. In this organ, their differentiation requires signals from the T cell receptor for antigen, from co-stimulatory molecules, as well as from cytokine-receptors. Here we focus on the cytokines implicated in thymic development of Treg, with a particular emphasis on the roles of interleukin-2 (IL-2) and IL-15. The more recently appreciated involvement of TGF-β in thymic Treg development is also briefly discussed. Finally, we discuss how cytokine-dependence of Treg development allows for temporal, quantitative, and potentially qualitative modulation of this process.

  4. Association of SNPs from IL1A, IL1B, and IL6 Genes with Human Cytomegalovirus Infection Among Pregnant Women.

    Science.gov (United States)

    Wujcicka, Wioletta Izabela; Wilczyński, Jan Szczęsny; Nowakowska, Dorota Ewa

    2017-05-01

    The study was aimed to estimate the role and prevalence rates of genotypes, haplotypes, and alleles, located within the single-nucleotide polymorphisms (SNPs) of interleukin (IL) 1A, IL1B, and IL6 genes, in the occurrence and development of human cytomegalovirus (HCMV) infection among pregnant women. A research was conducted in 129 pregnant women, out of whom, 65 were HCMV infected and 64 were age-matched control uninfected individuals. HCMV DNA was quantitated for UL55 gene by the real-time Q PCR in the body fluids. The genotypic statuses within the SNPs were determined by nested PCR-RFLP assays and confirmed, by sequencing for randomly selected representative PCR products. A relationship between the genotypes and alleles, as well as haplotypes and multiple variants in the studied polymorphisms, and the occurrence of HCMV infection in pregnant women, was determined using a logistic regression model. TT genotype within IL1A polymorphism significantly decreased the risk of HCMV infection (OR 0.32, 95% CI 0.09-1.05; p ≤ 0.050). Considering IL6 SNP, the prevalence rate of GC genotype was significantly decreased among the HCMV infected, compared to the uninfected control individuals (OR 0.45, 95% CI 0.21-0.99; p ≤ 0.050). Moreover, CC homozygotic status in IL6 SNP, found in pregnant women, significantly decreased the risk of congenital infection with HCMV in their offsprings (OR 0.12; p ≤ 0.050). In multiple SNP analysis, TC haplotype within the IL1 polymorphisms significantly decreased the risk of the infection in pregnant women (OR 0.38 95% CI 0.15-0.96; p ≤ 0.050). In addition, TTG complex variants for all the studied polymorphisms and TG variants for IL1B and IL6 SNPs were significantly more prevalent among the infected offsprings with symptomatic congenital cytomegaly than among the asymptomatic cases (p ≤ 0.050). In conclusion, the analyzed IL1A -889 C>T, IL1B +3954 C>T, and IL6 -174 G>C polymorphisms may be associated with the

  5. Novel Small Molecules Disabling the IL-6/IL-6R/GP130 Heterohexamer Complex

    Science.gov (United States)

    2013-10-01

    using the natural product madindoline A as a starting point for our studies. Madindoline A (MDL-A) is known to interact with the IL-6 receptor on the...the Leu57 site or the extra subpockets. Piperidine and cyclohexane , very common six member rings in drugs, were used to replace the aliphatic tail...center. In this case, however, Sharpless epoxidation failed to provide the desired product in sufficient yield, presumably due to the decrease in

  6. Evaluation of IL-4, IL-17, and IFN-γ Levels in PatientsWith Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mina Rohani Borj

    2017-03-01

    Full Text Available Introduction: Tumor growth depends on intrinsic properties of malignant tumor and tumor microenvironment. Cytokines are secreted substances of the tumor microenvironment which are widely produced by tumor and immune cells. The aim of this research was to evaluate concentrations of interleukin 4 (IL-4, interleukin 7 (IL-17 and interferon gamma (IFN-γ in the breast cancer microenvironment. Methods: One hundred sixteen women between 18-73 years of age (61.15 ± 24.39 were enrolled in this study. Based on pathologic diagnostic assessment, patients were divided into 2 categories: those affected with benign breast tumor, and the subjects suffering from malignant breast tumors. Biopsy specimens were collected. Following homogenization, IFN-γ, IL-17, and IL-4 concentrations were determined in tumor tissues, adjacent tissues of the tumor, and blood serum samples of these 2 groups of patients by enzyme-linked immunosorbent assay (ELISA method. Results: Concentrations of IFN-γ, IL-17, and IL-4 were measured in tumor tissue samples, adjacent tissues of the tumor, and blood serum samples in both groups. Malignant breast tumor samples had significantly higher concentrations of IL-4 and IL-17 compared with benign breast tumor samples. And also the concentration of IFN-γ in adjacent tissues of the tumor and in blood serums in patients with malignant breast tumors was significantly higher than that in the benign breast tumor samples. However, there was no significant difference between the concentration of IFN-γ in neoplastic breast tumor tissues and that in the benign breast tumor tissues (P > 0. 05. Conclusion: Our data indicated that IL-17 and IL-4 cytokines but not IFN-γ had higher concentrations in the subjects with malignant tumor compared with those with benign tumor. The present findings indicated that the concentrations of IL-4 and IL-17 in tumor tissues may be associated with the severity of breast malignancy.

  7. IL-34 Upregulated Th17 Production through Increased IL-6 Expression by Rheumatoid Fibroblast-Like Synoviocytes

    OpenAIRE

    Wang, Bing; Ma, Zijian; Wang, Miaomiao; Sun, Xiaotong; Tang, Yawei; Li, Ming; Zhang, Yan; Li, Fang; Li, Xia

    2017-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease which is characterized by synovial inflammation and cartilage damage for which causes articular dysfunction. Activation of fibroblast-like synoviocytes (FLS) is a critical step that promotes disease progression. In this study, we aimed to explore the effect of interleukin-34 (IL-34) on RA FLS as a proinflammatory factor and IL-34-stimulated FLS on the production of Th17. We found that serum IL-34 levels were increased compared to those...

  8. MEK1 Dependent and Independent ERK Activation Regulates IL-10 and IL-12 Production in Bone Marrow Derived Macrophages

    Science.gov (United States)

    Bouhamdan, Mohamad; Bauerfeld, Christian; Talreja, Jaya; Beuret, Laurent; Charron, Jean; Samavati, Lobelia

    2015-01-01

    The mitogen activated protein kinases ERK1/2 play an important role in response to toll like receptor (TLR) activation and cytokine production, including IL-10 and IL-12. Here, we examined the role of MEK1 in ERK1/2 activation in response to TLR4 agonist by using bone marrow-derived macrophages (BMDMs) from wild type (WT) and Mek1d/dSox2Cre mice. Our data demonstrates that MEK1 is essential for ERK1/2 activation in response to LPS. Furthermore, stimulation of the TLR4 receptor of BMDMs derived from Mek1d/d Sox2Cre mice showed enhanced STAT4 phosphorylation and increased IL-12 secretion, but exhibited a significantly lower IL-10 production as compared to WT macrophages. Most interestingly, TLR ligation in the presence of recombinant IL-10 (rIL-10) or retinoic acid (RA) led to ERK1/2 activation independent of MEK1 in BMDMs derived from Mek1d/dSox2Cre mice and led to inhibition of STAT4 and decreased IL-12 levels. Collectively, these data suggest that MEK1 is required for TLR4 mediated ERK activation and in turn regulates production of IL-10 and IL-12. It also indicates that ERK1/2 can be activated independent of MEK1 in the presence of IL-10 and RA and this activation negatively regulates IL-12, but positively regulates IL-10 production. These findings may have significant implications for the development of drugs that modulate MEK1 activity in the treatment of inflammatory, autoimmune and proliferative diseases such as cancer. PMID:26208884

  9. Impact of aerobic exercise on levels of IL-4 and IL-10: results from two randomized intervention trials.

    Science.gov (United States)

    Conroy, Shannon M; Courneya, Kerry S; Brenner, Darren R; Shaw, Eileen; O'Reilly, Rachel; Yasui, Yutaka; Woolcott, Christy G; Friedenreich, Christine M

    2016-09-01

    The mechanisms whereby regular exercise reduces chronic inflammation remain unclear. We investigated whether regular aerobic exercise alters basal levels of interleukin (IL)-10 and IL-4 in two randomized trials of physical activity. The Alberta Physical Activity and Breast Cancer Prevention Trial (ALPHA, n = 320) and the Breast Cancer and Exercise Trial in Alberta (BETA, n = 400) were two-center, two-armed randomized trials in inactive, healthy, postmenopausal women. Both trials included an exercise intervention prescribed five times/week and no dietary changes. In ALPHA, the exercise group was prescribed 225 min/week versus no activity in the controls. BETA examined dose-response effects comparing 300 (HIGH) versus 150 (MODERATE) min/week. Plasma concentrations of IL-10 and IL-4 were measured at baseline, 6, and 12 months. Intention-to-treat (ITT) analysis was performed using linear mixed models adjusted for baseline biomarker concentrations. Circulating anti-inflammatory cytokine levels decreased among all groups, with percent change ranging from -3.4% (controls) to -8.2% (HIGH) for IL-4 and -1.6% (controls) to -7.5% (HIGH) for IL-10. No significant group differences were found for IL-4 (ALPHA P = 0.54; BETA P = 0.32) or IL-10 (ALPHA P = 0.84; BETA P = 0.68). Some evidence for moderation of the effect of exercise by baseline characteristics was found for IL-10 but not for IL-4. Results from these two large randomized aerobic exercise intervention trials suggest that aerobic exercise does not alter IL-10 or IL-4 in a manner consistent with chronic disease and cancer prevention. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  10. Assemblare il genere nello sport: il caso controverso di Caster Semenya

    Directory of Open Access Journals (Sweden)

    Serena Naim

    2013-04-01

    Full Text Available Questa ricerca mira a indagare le strategie di gestione delle “anomalie” di genere in contesti di forte segregazione tra i sessi. In particolare, il tema che ci interessa trattare in queste pagine riguarda il modo in cui il mondo sportivo affronta, sia in termini tecnico-scientifici sia in termini narrativi, i casi di atlete che, per caratteristiche fisiche di vario tipo, non rientrano negli standard pensati per chi compete nelle categorie femminili. Cercheremo di capire in che modo l'approccio narrativo si intreccia a quello tecnico-scientifico, e quali saranno le possibili soluzioni al problema. Lo sport si rivela in questo senso un terreno estremamente favorevole allo svolgimento di questa ricerca, per tre caratteristiche particolari: in primo luogo, come dicevamo, vige una stretta separazione tra uomini e donne; in secondo luogo, è oggetto di grande interesse mediatico e dunque di una florida produzione narrativa; infine, è un ambito fortemente medicalizzato, sia per questioni di salute psico-fisica degli atleti, sia per questioni di controllo del doping.

  11. GeoCallCenter: quando il GIS entra in simbiosi con il telefono

    Directory of Open Access Journals (Sweden)

    Ivan Tani

    2007-03-01

    Full Text Available Hera, con 2,5 milioni di utenti e 2,1 miliardi di euro di ricavi (2005, rappresenta la più grande azienda multiutility italiana e una delle maggiori aziende del settore a livello europeo. Tra i servizi erogati da Hera c’è la distribuzione di energia elettrica, gas, acqua, la depurazione delle acque reflue, lo smaltimento dei rifiuti e la gestione della pubblicailluminazione e delle reti semaforiche. L’idea di un SIT di holding prende corpo nel 2003 con l’obiettivo di costituire un punto di coordinamento nel gestire in maniera omogenea l’informazione geografica e gli applicativi per il trattamento delle medesime, per tutto il gruppo. Il progetto eredita i livelli funzionali e la struttura trasparente del precedente SIT di Seabo S.p.A., in cui aspetti territoriali, ambientali, di gestione, di pianificazione e di servizio al cliente sono stati considerati contestualmente allo sviluppo complessivo del sistema informativo aziendale.

  12. Information Literacy (IL Intervention Workshop has Positive, but Limited, Effects on Undergraduate Students’ IL Skills

    Directory of Open Access Journals (Sweden)

    Lisa Shen

    2014-07-01

    Full Text Available Objective – To evaluate the impact of an educational intervention workshop on students’ information literacy (IL skills and self-perception of their own IL knowledge. Design – Quasi-experimental design with control groups and semi-structured interviews. Setting – Two community colleges in the United States of America, one in a rural setting and one in an urban setting. Subjects – Ninety-two students enrolled in an entry-level English course, who scored below proficiency (65% on the Information Literacy Test (ILT. Methods – One hundred students from each college took the pre-session ILT and an IL self assessment survey at the beginning of the Spring 2011 semester. The ILT used was developed and validated by James Madison University (Wise, Cameron, Yang, & Davis, n.d. and measures understanding of all the Association of College and Research Libraries (ACRL Information Literacy Competency Standards (ACRL, 2000, pp. 2-3 except Standard 4. For motivation, students each received $20 for their efforts and were told those who scored in the top 15% would enter a draw to win one of two additional prizes of $50. Those who scored below the ILT proficiency level of 65% were invited to participate in the quasi-experiment.

  13. EFFECTS OF γс-CYTOKINES (IL-2, IL-7 AND IL-15 UPON IN VITRO MATURATION AND DIFFERENTIATION OF CD4+CD45RО+/CD8+CD45RО+ T CELLS

    Directory of Open Access Journals (Sweden)

    K. A. Yurova

    2018-01-01

    Full Text Available Effect of γс-cytokines (IL-2, IL-7 и IL-15 upon maturation and differentiation of cytotoxic and helper CD45RО+ Tcell population was studied in the homeostatic in vitro culture conditions. We have found that IL-2, IL-7 and IL-15 mediate maturation and differentiation of CD8 T cells central memory, replenishing the population of cells that exhibit effector functions. Action of IL-2 on CD4+ central memory T cells is accociated with generation of effector memory cells by reducing the number of immature effectors (CD62L–CD27+, whereas IL-7 promotes the formation of immature (CD62L–CD27+ effectors. IL-2, IL-7 and IL-15 initiate formation of terminally-differentiated cells in a subpopulation of CD8+CD45RO+ lymphocytes, providing a stable immunological memory to a pathogen reinfestation. 

  14. Structure analysis of the IL-5 ligand-receptor complex reveals a wrench-like architecture for IL-5Rα.

    Science.gov (United States)

    Patino, Edwin; Kotzsch, Alexander; Saremba, Stefan; Nickel, Joachim; Schmitz, Werner; Sebald, Walter; Mueller, Thomas D

    2011-12-07

    Interleukin-5 (IL-5) is the key mediator for the function of eosinophil granulocytes, whose deregulation is characteristic of hypereosinophilic diseases and presumably contributes to allergic asthma. IL-5 signaling involves two transmembrane receptors, IL-5Rα and the common β chain, which upon formation of the ternary complex activate the JAK/STAT signaling cascade. To investigate the mechanism underlying ligand-receptor recognition, we determined the structure of IL-5 bound to the extracellular domain of IL-5Rα. IL-5 makes contact with all three fibronectin III-like domains of IL-5Rα, with the receptor architecture resembling a wrench. Mutagenesis data provide evidence that this wrench-like architecture is likely preformed. The structure demonstrates that for steric reasons, homodimeric IL-5 can bind only one receptor molecule, even though two equivalent receptor-binding sites exist. In regard to strong efforts being made to develop IL-5 antagonists for treating asthma and hypereosinophilic diseases, the advances in molecular understanding provided by this structure are of greatest value. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Peripheral blood MDSCs, IL-10 and IL-12 in children with asthma and their importance in asthma development.

    Science.gov (United States)

    Zhang, Yan-Li; Luan, Bin; Wang, Xiu-Fang; Qiao, Jun-Ying; Song, Li; Lei, Rui-Rui; Gao, Wei-Xia; Liu, Ying

    2013-01-01

    To investigate myeloid-derived suppressor cell (MDSC) accumulation and interleukin 10 (IL-10) and interleukin 12 (IL-12) levels during the onset of asthma in both pediatric patients and mouse models, as well as their possible roles in the development of asthma. Peripheral blood samples were gathered from children with asthma attacks (attack group) and alleviated asthma (alleviated group), as well as two control groups, children with pneumonia and healthy children. The pathological characteristics of asthma in asthmatic mice, budesonide-treated asthmatic mice, and normal control mice were also evaluated by immunohistochemistry (IHC) and hematoxylin and eosin (H&E) staining. MDSC accumulation and serum IL-10 levels were significantly elevated in the children with asthma compared with the budesonide-treated alleviated group, normal healthy controls, and pneumonia controls (p0.05). The level of serum IL-12 in the asthmatic children was drastically reduced compared to the budesonide-treated alleviated group, healthy controls, and pneumonia controls (pasthma was positively correlated with the level of serum IL-10 and negatively correlated with the level of serum IL-12. The levels of MDSCs and IL-10 in asthmatic mice were significantly higher than those in the normal control mice (both pasthma, the accumulation of MDSCs and the level of serum IL-10 increase, while the level of IL-12 decreases. These fluctuations may play an important role in the development of asthma.

  16. Distinct licensing of IL-18 and IL-1β secretion in response to NLRP3 inflammasome activation.

    Directory of Open Access Journals (Sweden)

    Rebecca L Schmidt

    Full Text Available Inflammasome activation permits processing of interleukins (IL-1β and 18 and elicits cell death (pyroptosis. Whether these responses are independently licensed or are "hard-wired" consequences of caspase-1 (casp1 activity has not been clear. Here, we show that that each of these responses is independently regulated following activation of NLRP3 inflammasomes by a "non-canonical" stimulus, the secreted Listeria monocytogenes (Lm p60 protein. Primed murine dendritic cells (DCs responded to p60 stimulation with reactive oxygen species (ROS production and secretion of IL-1β and IL-18 but not pyroptosis. Inhibitors of ROS production inhibited secretion of IL-1β, but did not impair IL-18 secretion. Furthermore, DCs from caspase-11 (casp11-deficient 129S6 mice failed to secrete IL-1β in response to p60 but were fully responsive for IL-18 secretion. These findings reveal that there are distinct licensing requirements for processing of IL-18 versus IL-1β by NLRP3 inflammasomes.

  17. Distinct Licensing of IL-18 and IL-1β Secretion in Response to NLRP3 Inflammasome Activation

    Science.gov (United States)

    Schmidt, Rebecca L.; Lenz, Laurel L.

    2012-01-01

    Inflammasome activation permits processing of interleukins (IL)-1β and 18 and elicits cell death (pyroptosis). Whether these responses are independently licensed or are “hard-wired” consequences of caspase-1 (casp1) activity has not been clear. Here, we show that that each of these responses is independently regulated following activation of NLRP3 inflammasomes by a “non-canonical” stimulus, the secreted Listeria monocytogenes (Lm) p60 protein. Primed murine dendritic cells (DCs) responded to p60 stimulation with reactive oxygen species (ROS) production and secretion of IL-1β and IL-18 but not pyroptosis. Inhibitors of ROS production inhibited secretion of IL-1β, but did not impair IL-18 secretion. Furthermore, DCs from caspase-11 (casp11)-deficient 129S6 mice failed to secrete IL-1β in response to p60 but were fully responsive for IL-18 secretion. These findings reveal that there are distinct licensing requirements for processing of IL-18 versus IL-1β by NLRP3 inflammasomes. PMID:23028835

  18. Effects of plaque, psychological stress and gender on crevicular Il-1beta and Il-1ra secretion.

    Science.gov (United States)

    Waschul, Bernd; Herforth, Armin; Stiller-Winkler, Renate; Idel, Helga; Granrath, Nicole; Deinzer, Renate

    2003-03-01

    The study aimed to analyse (a) whether the effects of psychological stress and of experimental gingivitis on interleukin-1beta (Il-1beta) described before are compensated by concomitant increases in Il-1 receptor antagonist (Il-1ra), and (b) whether there do exist any gender differences in the Il-1 responses to experimental gingivitis and to psychological stress. Thirteen medical students participating in a major academic exam (seven males, six females) and 14 medical students without academic stress (eight males, six females) refrained from oral hygiene in two antagonistic quadrants for 28 days (plaque) while they maintained oral hygiene in the remaining quadrants (hygiene). Weekly crevicular fluid samples of plaque and hygiene sites were assayed for Il-1beta and Il-1ra. Neither stress nor experimental gingivitis exerted significant effects on Il-1ra. In controls, we observed significant gender and gender x time effects on Il-1beta; comparing stress groups, gender x time and stress x gender x time interactions became significant. Women show a reduced Il-1beta response to plaque at rest and an increased response under stress. Similar results were found with respect to bleeding on probing. Gender must be controlled in studies on periodontal responses to pathogens. Stress plays a role in these responses.

  19. GM-CSF and IL-4 produced by NKT cells inversely regulate IL-1β production by macrophages.

    Science.gov (United States)

    Ahn, Sehee; Jeong, Dongjin; Oh, Sae Jin; Ahn, Jiye; Lee, Seung Hyo; Chung, Doo Hyun

    2017-02-01

    Natural Killer T (NKT) cells are distinct T cell subset that link innate and adaptive immune responses. IL-1β, produced by various immune cells, plays a key role in the regulation of innate immunity in vivo. However, it is unclear whether NKT cells regulate IL-1β production by macrophages. To address this, we co-cultured NKT cells and peritoneal macrophages in the presence of TCR stimulation and inflammasome activators. Among cytokines secreted from NKT cells, GM-CSF enhanced IL-1β production by macrophages via regulating LPS-mediated pro-IL-1β expression and NLRP3-dependent inflammasome activation, whereas IL-4 enhanced M2-differentiation of macrophages and decreased IL-1β production. Together, our findings suggest the NKT cells have double-sided effects on IL-1β-mediated innate immune responses by producing IL-4 and GM-CSF. These findings may be helpful for a comprehensive understanding of NKT cell-mediated regulatory mechanisms of the pro-inflammatory effects of IL-1β in inflammatory diseases in vivo. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  20. Serum IL-6 level and associated factors: hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Seifi S, Mokhtari A

    2008-07-01

    Full Text Available "nBackground: The annual amount of mortality in ESRD exceeds the expectation and represents the recent evidences of the inflammation as its etiology. The etiology of inflammation is not clearly known. Chronic inflammation is a dominant occurrence of ESRD which increases the risk of atherosclerosis, malnutrition and peripheral vascular disease. Inflammatory responses are orchestrated by cytokines. Some of the proinflammatory cytokines like IL-6 have a crucial role in this phenomenon. The IL-6 and its receptor activity is up regulated in ESRD patients and the increased level of IL-6 predicts cardiovascular mortality and morbidity in normal and CRF patients. This study devotes itself to determining the serum level of IL-6 and factors affecting it in patients undergoing chronic hemodialysis in Imam Khomeini Hospital which can represent the Iranian Society. By identifying factors affecting the serum level of IL-6 and high-risk patients we can provide treatment possibilities, a decrease in mortality and an improvement in its prognosis. "n"nMethods: In this study 42 patients in Imam Dialysis Center were chosen and their serum IL-6 levels were measured at 2 times at three month interval and at the same time blood sample analysis were done for the following: Alb CPR, Ca, P, PTH, TIBC, Ferritin, TG, Chol, LDL, HDL, Uric Acid, Hb, WBC and urea."n"nResults: The mean serum level of IL-6 in hemodialysis patients was 6.35±4.47pg/ml (minimum: 0.55, maximum: 18.25 with the normal range of 1.3±3.2pg/ml."n"nConclusions: The IL-6 level was higher than normal range in the 52% of the patients. The serum IL-6 level had a significant correlations with CPR, Ferritin, TIBC, WBC and their serum IL-6 level was significantly higher in patients with hypertension, but no significant correlation was observed between other parameters and IL-6

  1. IL-6 Potentiates Tumor Resistance to Photodynamic Therapy (PDT)

    Science.gov (United States)

    Brackett, Craig M.; Owczarczak, Barbara; Ramsey, Kimberley; Maier, Patricia G.; Gollnick, Sandra O.

    2013-01-01

    Background and Objective Photodynamic therapy (PDT) is an anticancer modality approved for the treatment of early disease and palliation of late stage disease. PDT of tumors results in the generation of an acute inflammatory response. The extent and duration of the inflammatory response is dependent upon the PDT regimen employed and is characterized by rapid induction of proinflammatory cytokines, such as IL-6, and activation and mobilization of innate immune cells. The importance of innate immune cells in long-term PDT control of tumor growth has been well defined. In contrast the role of IL-6 in long-term tumor control by PDT is unclear. Previous studies have shown that IL-6 can diminish or have no effect on PDT antitumor efficacy. Study Design/Materials and Methods In the current study we used mice deficient for IL-6, Il6−/−, to examine the role of IL-6 in activation of antitumor immunity and PDT efficacy by PDT regimens known to enhance antitumor immunity. Results Our studies have shown that elimination of IL-6 had no effect on innate cell mobilization into the treated tumor bed or tumor draining lymph node (TDLN) and did not affect primary antitumor T-cell activation by PDT. However, IL-6 does appear to negatively regulate the generation of antitumor immune memory and PDT efficacy against murine colon and mammary carcinoma models. The inhibition of PDT efficacy by IL-6 appears also to be related to regulation of Bax protein expression. Increased apoptosis was observed following treatment of tumors in Il6−/− mice 24 hours following PDT. Conclusions The development of PDT regimens that enhance antitumor immunity has led to proposals for the use of PDT as an adjuvant treatment. However, our results show that the potential for PDT induced expression of IL-6 to enhance tumor survival following PDT must be considered. PMID:22057495

  2. DIFFERENTIAL BINDING OF HUMAN INTERLEUKIN-1 (IL-1) RECEPTOR ANTAGONIST TO NATURAL AND RECOMBINANT SOLUBLE AND CELLULAR IL-1 TYPE-I RECEPTORS

    DEFF Research Database (Denmark)

    Svenson, Morten; Nedergaard, Susanne; Heegaard, Peter M. H.

    1995-01-01

    antagonist (IL-1ra). Recombinant soluble human IL-1RI expressed in COS cells (sIL-1RI) consists of the extracellular part of the receptor and binds all three known IL-1 species but preferentially to IL-1ra. We further characterized the sizes and binding of IL-1raBF and sIL-1RI to IL-1ra by polyacrylamide gel...... electrophoresis in the presence of sodium dodecylsulfate, ligand binding interference analyses, N-glycosidase treatment, concanavalin A affinity chromatography, and with the use of monoclonal antibodies (mAb) to human recombinant IL-1ra. We also evaluated the binding of IL-1ra to cellular IL-1RI on MRC5...... binding of both molecules to IL-1ra. Both factors blocked binding of IL-1ra to cellular IL-1RI, as did mAb to IL-1ra, but the sites on IL-1ra which bound to the mAb, and to IL-1raBF and sIL-1RI, differed. We conclude that there are important differences between the natural and recombinant forms of soluble...

  3. Regulation and functions of the IL-10 family of cytokines in inflammation and disease.

    Science.gov (United States)

    Ouyang, Wenjun; Rutz, Sascha; Crellin, Natasha K; Valdez, Patricia A; Hymowitz, Sarah G

    2011-01-01

    The IL-10 family of cytokines consists of nine members: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, and the more distantly related IL-28A, IL-28B, and IL-29. Evolutionarily, IL-10 family cytokines emerged before the adaptive immune response. These cytokines elicit diverse host defense mechanisms, especially from epithelial cells, during various infections. IL-10 family cytokines are essential for maintaining the integrity and homeostasis of tissue epithelial layers. Members of this family can promote innate immune responses from tissue epithelia to limit the damage caused by viral and bacterial infections. These cytokines can also facilitate the tissue-healing process in injuries caused by infection or inflammation. Finally, IL-10 itself can repress proinflammatory responses and limit unnecessary tissue disruptions caused by inflammation. Thus, IL-10 family cytokines have indispensable functions in many infectious and inflammatory diseases.

  4. Association of IL-10, IL-4, and IL-28B gene polymorphisms with spontaneous clearance of hepatitis C virus in a population from Rio de Janeiro.

    Science.gov (United States)

    Ramos, Juliene Antonio; Silva, Rosane; Hoffmann, Luísa; Ramos, Ana Lucia Araújo; Cabello, Pedro Hernan; Urményi, Turán Péter; Villella-Nogueira, Cristiane Alves; Lewis-Ximenez, Lia; Rondinelli, Edson

    2012-09-17

    Cytokines play an important role in the regulation of the immune response. In hepatitis C virus (HCV) infection, cytokine levels may influence the outcome of acute HCV infection. Polymorphisms in cytokine genes have been associated to different expression levels in response to infection. This study was carried out to investigate the association of several cytokine gene polymorphisms with disease outcome in HCV-infected patients. Patients with chronic or spontaneously resolved HCV infection were included in a cross-sectional study. A comparative analysis was performed between the groups regarding frequency distribution of the following cytokines' gene polymorphisms: IL-10 (-1082 A/G; -819 T/C; -592 A/C), IL-4 (+33C/T), IFN-γ (+874 T/A), TNF-α (-238 G/A and -308 G/A) and IL-28B (rs12979860 C/T and rs8099917 T/G). Eighteen patients with spontaneous viral clearance and 161 with chronic HCV infection were included. In the comparative analysis, the GG genotype of the IL-10 polymorphism -1082A/G was more frequent in patients with spontaneous viral clearance when compared to patients with chronic HCV (41.2% vs 6.2%; p = 0.001). This association was also found for the CC genotype of the IL-4 polymorphism +33C/T (72.2% vs 36.7%; p = 0.017) and the CC and TT genotypes of the IL-28B polymorphisms rs 12979860 and rs 8099917 (88.9% vs 30.3%; p < 0.001 and 88.9% vs 49.6%; p = 0.002). The IL10 (A-1082 G) and IL-28B (Crs12979860T) gene polymorphisms showed odds ratios of 12.848 and 11.077, respectively, and thus may have a greater influence on HCV spontaneous viral clearance. The IFN-γ (+874 T/A), TNF-α (-238 G/A and -308 G/A) polymorphisms did not show significant association with spontaneous viral clearance or chronicity. The G allele for IL-10 (-1082 A/G), the C allele for IL-4 (+3 C/T) and the C and T alleles for IL-28B (rs12979860 and rs8099917, respectively) are associated with spontaneous viral clearance in hepatitis C infection.

  5. menzogna e sortilegio, il primo romanzo di elsa morante

    African Journals Online (AJOL)

    User

    Il tono dei commentatori fu generalmente alquanto riservato, con un paio di eccezioni degne di nota ─ per la ferocia, non per l'entusiasmo, di certo. Di recensioni entusiastiche il lunghissimo romanzo non ne ebbe neppure una. In linea di massima i recensori sono piuttosto rispettosi del raffinato livello linguistico e stilistico ...

  6. IL-10 gene therapy prevents TNBS-induced colitis

    NARCIS (Netherlands)

    Lindsay, J.; van Montfrans, C.; Brennan, F.; van Deventer, S.; Drillenburg, P.; Hodgson, H.; te Velde, Anje; Sol Rodriguez Pena, M.

    2002-01-01

    The transfer of genes encoding immunomodulatory proteins to the intestinal mucosa is a promising new approach to the treatment of Crohn's disease (CD). This study investigates the therapeutic efficacy of an adenoviral vector encoding IL-10 (AdvmuIL-10) in experimental colitis. BALB/c mice were

  7. L’hackathon è la porta per il successo

    Directory of Open Access Journals (Sweden)

    Mauro Salvemini

    2015-06-01

    Full Text Available L’hackathon è la porta per il successo: questa affermazione al momento attuale sembra essere dimostrata da paesi che stanno usando la tecnologia informatica per il progresso in genere e per lo sviluppo economico in particolare.

  8. I>Lo specchio frammentato ed il pagliaccio piangente : alienation ...

    African Journals Online (AJOL)

    Quest'articolo esamina il modo in cui il cinema di Nanni Moretti usa uno sguardo autoriflessivamente critico per parlare della condizione frammentata ed alienata di un soggetto maschile, italiano e di sinistra, nella tarda età capitalista. L'articolo mette a fuoco come l'uso morettiano dell' umorismo, con palesi tratti ...

  9. Il comico come strategia in Gianni Celati & Co

    DEFF Research Database (Denmark)

    2012-01-01

    Il presente volume raccoglie i contributi di un convegno internazionale svoltosi a Copenaghen nel maggio del 2009 per iniziativa di Lene Waage Petersen, che ha il merito di aver introdotto le opere di Gianni Celati e Ermanno Cavazzoni in Danimarca, e di aver tradotto Narratori delle pianure in da...

  10. Kaempferol impedes IL-32-induced monocyte-macrophage differentiation.

    Science.gov (United States)

    Nam, Sun-Young; Jeong, Hyun-Ja; Kim, Hyung-Min

    2017-08-25

    Kaempferol possesses a wide range of therapeutic properties, including antioxidant, anti-inflammatory, and anticancer properties. The present study sought to evaluate the effects and possible pharmacological mechanisms of kaempferol on interleukin (IL)-32-induced monocyte-macrophage differentiation. In this study, we performed flow cytometry assay, immunocytochemical staining, quantitative real-time PCR, enzyme-linked immuno sorbent assay, caspase-1 assay, and Western blotting to observe the effects and underlying mechanisms of kaempferol using the human monocyte cell line THP-1. The flow cytometry, immunocytochemical staining, and real-time PCR results show that kaempferol attenuated IL-32-induced monocyte differentiation to product macrophage-like cells. Kaempferol decreased the production and mRNA expression of pro-inflammatory cytokines, in this case thymic stromal lymphopoietin (TSLP), IL-1β, tumor necrosis factor (TNF)-α, and IL-8. Furthermore, kaempferol inhibited the IL-32-induced activation of p38 and nuclear factor-κB in a dose-dependent manner in THP-1 cells. Kaempferol also ameliorated the lipopolysaccharide-induced production of the inflammatory mediators TSLP, IL-1β, TNF-α, IL-8, and nitric oxide of macrophage-like cells differentiated by IL-32. In brief, our findings may provide new mechanistic insights into the anti-inflammatory effects of kaempferol. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Information Literacy (IL) learning experiences: A literature review ...

    African Journals Online (AJOL)

    This paper is a review of extant literature on information literacy. The study reports literature on IL learning experiences in institutions across the globe. It also discusses the spectrum of literacy to give information literacy a context. Furthermore, the paper presents an overview of IL learning initiatives in academic ...

  12. Il processo agrario italiano alle soglie del 2000

    Directory of Open Access Journals (Sweden)

    Alberto Germanò

    2015-01-01

    Full Text Available Il nuovo ordinamento giudiziario italiano: il giudice unido di primo grado. La conservazione delle Sezione specializzate agrarie. La partecipazione degli esperti o giudici laici nei processi agrarie. L'attività istruttoria nel processo civile moderno. Le probabili ragioni della conservazione delle Sezioni specalizzate. Considerazioni finali

  13. Inflammasome-independent regulation of IL-1-family cytokines.

    Science.gov (United States)

    Netea, Mihai G; van de Veerdonk, Frank L; van der Meer, Jos W M; Dinarello, Charles A; Joosten, Leo A B

    2015-01-01

    Induction, production, and release of proinflammatory cytokines are essential steps to establish an effective host defense. Cytokines of the interleukin-1 (IL-1) family induce inflammation and regulate T lymphocyte responses while also displaying homeostatic and metabolic activities. With the exception of the IL-1 receptor antagonist, all IL-1 family cytokines lack a signal peptide and require proteolytic processing into an active molecule. One such unique protease is caspase-1, which is activated by protein platforms called the inflammasomes. However, increasing evidence suggests that inflammasomes and caspase-1 are not the only mechanism for processing IL-1 cytokines. IL-1 cytokines are often released as precursors and require extracellular processing for activity. Here we review the inflammasome-independent enzymatic processes that are able to activate IL-1 cytokines, paying special attention to neutrophil-derived serine proteases, which subsequently induce inflammation and modulate host defense. The inflammasome-independent processing of IL-1 cytokines has important consequences for understanding inflammatory diseases, and it impacts the design of IL-1-based modulatory therapies.

  14. Hydrochlorothiazide increases interleukin-1 beta (IL-1β) secretion ...

    African Journals Online (AJOL)

    Previous studies showed that individuals with essential hypertension had increased interleukin-1beta (IL-1β) secretion by peripheral blood mononuclear cells (PBMCs) and also valsartan and simvastatin reduced this inflammatory marker. In this study, the effect of hydrochlorothiazide on IL-1β secretion by PBMCs in healthy ...

  15. Role of IL-1beta in type 2 diabetes

    DEFF Research Database (Denmark)

    Dinarello, Charles A; Donath, Marc Y; Mandrup-Poulsen, Thomas

    2010-01-01

    To understand the role of inflammation as the fundamental cause of type 2 diabetes and specifically to examine the contribution of IL-1beta.......To understand the role of inflammation as the fundamental cause of type 2 diabetes and specifically to examine the contribution of IL-1beta....

  16. Integrated Library System (ILS): An Option for Library and ...

    African Journals Online (AJOL)

    The purpose of this paper is to review the capability of integrated library system as an option for managing library information resources using Koha ILS used at Babcock University as a case study. The paper is a review of the functions and performance of Koha ILS. It also includes personal experiences of librarians and the ...

  17. 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, ...

  18. Information Literacy (IL) teaching and learning: a literature review ...

    African Journals Online (AJOL)

    The paper is largely based on review of existing literature on teaching and learning Information Literacy (IL), both online and in print. It reports on studies about the teaching and learning of IL in some institutions of higher learning. It also discusses lists of competencies, and descriptions of information literacy programmes ...

  19. Preferential binding to Elk-1 by SLE-associated IL10 risk allele upregulates IL10 expression.

    Directory of Open Access Journals (Sweden)

    Daisuke Sakurai

    Full Text Available Immunoregulatory cytokine interleukin-10 (IL-10 is elevated in sera from patients with systemic lupus erythematosus (SLE correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA (P = 2.7×10⁻⁸, OR = 1.30, but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively, and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1 detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele

  20. Peripheral blood MDSCs, IL-10 and IL-12 in children with asthma and their importance in asthma development.

    Directory of Open Access Journals (Sweden)

    Yan-Li Zhang

    Full Text Available OBJECTIVE: To investigate myeloid-derived suppressor cell (MDSC accumulation and interleukin 10 (IL-10 and interleukin 12 (IL-12 levels during the onset of asthma in both pediatric patients and mouse models, as well as their possible roles in the development of asthma. METHODS: Peripheral blood samples were gathered from children with asthma attacks (attack group and alleviated asthma (alleviated group, as well as two control groups, children with pneumonia and healthy children. The pathological characteristics of asthma in asthmatic mice, budesonide-treated asthmatic mice, and normal control mice were also evaluated by immunohistochemistry (IHC and hematoxylin and eosin (H&E staining. RESULTS: MDSC accumulation and serum IL-10 levels were significantly elevated in the children with asthma compared with the budesonide-treated alleviated group, normal healthy controls, and pneumonia controls (p0.05. The level of serum IL-12 in the asthmatic children was drastically reduced compared to the budesonide-treated alleviated group, healthy controls, and pneumonia controls (p<0.05, whereas the latter three groups showed no significant differences in their serum IL-12 levels. The percentage of MDSCs in children with asthma was positively correlated with the level of serum IL-10 and negatively correlated with the level of serum IL-12. The levels of MDSCs and IL-10 in asthmatic mice were significantly higher than those in the normal control mice (both p<0.05 and were reduced after budesonide treatment (both p<0.05. IL-12 expression in the asthmatic mice was significantly lower than the control and was increased upon budesonide treatment (both p<0.05. CONCLUSION: During the onset of asthma, the accumulation of MDSCs and the level of serum IL-10 increase, while the level of IL-12 decreases. These fluctuations may play an important role in the development of asthma.

  1. Changes of serum IL-2, IL-4, IL-10 and IFN-γ levels after treatment with 131I-17-allylamino-17-demethoxygeldanamycin in VX2 rabbit models

    International Nuclear Information System (INIS)

    Gao Wen; Liu Lu; Zhou Yun

    2007-01-01

    Objective: To study the influence of 131 I-17-allylamino-17-demethoxygeldanamycin( 131 I-17-AAG) therapy on immune function in VX2 rabbit models with transplanted liver cancer. Methods: Serum IL-2, IL-4, IL-10 and IFN-γ levels were measured with RIA in 8 VX2 rabbit models with transplanted liver cancer 1-2 weeks after 10mCi 131 I-17-AAG treatment as well as in 8 controls rabbits (models with tumor but without treatment). Results: 1 week after 10mCi 131 I treatment, the serum IL - 2 and IFN-γ levels were significantly lower in the treated rabbits than those in controls (P 0.05). Serum IL-4 and IL-10 levels in the treated rabbits (both at 1 and 2 week) were not significantly different from those in controls (P>0.05). Conclusion: 131 I-17-AAG treatment had transient effects on cellular immunity with no influence on humoral immunity. As a whole, it is a safe to treat VX2 rabbit models with this preparation. (authors)

  2. Smokers with CT detected emphysema and no airway obstruction have decreased plasma levels of EGF, IL-15, IL-8 and IL-1ra.

    Directory of Open Access Journals (Sweden)

    Juan P de-Torres

    Full Text Available RATIONALE: Low-grade inflammation and emphysema have been shown to be associated with an increased risk of lung cancer. However, the systemic inflammatory response in patients with emphysema is still unknown. OBJECTIVE: TO COMPARE THE PLASMA CYTOKINE PROFILES IN TWO GROUPS OF CURRENT OR FORMER SMOKERS WITHOUT AIRWAY OBSTRUCTION: a control group of individuals without computed tomography (CT detected emphysema vs. a study group of individuals with CT detected emphysema. METHODS: Subjects underwent a chest CT, spirometry, and determination of EGF, IL-15, IL-1ra, IL-8, MCP-1, MIP-1β, TGFα, TNFα, and VEGF levels in plasma. Cytokine levels in each group were compared adjusting for confounding factors. RESULTS: 160 current smokers and former smokers without airway obstruction participated in the study: 80 without emphysema and 80 subjects with emphysema. Adjusted group comparisons revealed significant reductions in EGF (-0.317, p = 0.01, IL-15 (-0.21, p = 0.01, IL-8 (-0.180, p = 0.02 and IL-1ra (-0.220, p = 0.03 in subjects with emphysema and normal spirometry. CONCLUSIONS: Current or former smokers expressing a well-defined disease characteristic such as emphysema, has a specific plasma cytokine profile. This includes a decrease of cytokines mainly implicated in activation of apoptosis or decrease of immunosurveillance. This information should be taken into account when evaluated patients with tobacco respiratory diseases.

  3. The interleukin (IL)-1 cytokine family--Balance between agonists and antagonists in inflammatory diseases.

    Science.gov (United States)

    Palomo, Jennifer; Dietrich, Damien; Martin, Praxedis; Palmer, Gaby; Gabay, Cem

    2015-11-01

    The interleukin (IL)-1 family of cytokines comprises 11 members, including 7 pro-inflammatory agonists (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, IL-36γ) and 4 defined or putative antagonists (IL-1R antagonist (IL-1Ra), IL-36Ra, IL-37, and IL-38) exerting anti-inflammatory activities. Except for IL-1Ra, IL-1 cytokines do not possess a leader sequence and are secreted via an unconventional pathway. In addition, IL-1β and IL-18 are produced as biologically inert pro-peptides that require cleavage by caspase-1 in their N-terminal region to generate active proteins. N-terminal processing is also required for full activity of IL-36 cytokines. The IL-1 receptor (IL-1R) family comprises 10 members and includes cytokine-specific receptors, co-receptors and inhibitory receptors. The signaling IL-1Rs share a common structure with three extracellular immunoglobulin (Ig) domains and an intracellular Toll-like/IL-1R (TIR) domain. IL-1 cytokines bind to their specific receptor, which leads to the recruitment of a co-receptor and intracellular signaling. IL-1 cytokines induce potent inflammatory responses and their activity is tightly controlled at the level of production, protein processing and maturation, receptor binding and post-receptor signaling by naturally occurring inhibitors. Some of these inhibitors are IL-1 family antagonists, while others are IL-1R family members acting as membrane-bound or soluble decoy receptors. An imbalance between agonist and antagonist levels can lead to exaggerated inflammatory responses. Several genetic modifications or mutations associated with dysregulated IL-1 activity and autoinflammatory disorders were identified in mouse models and in patients. These findings paved the road to the successful use of IL-1 inhibitors in diseases that were previously considered as untreatable. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Il cerchio della paranoia politica. Possibili linee di frattura

    Directory of Open Access Journals (Sweden)

    Laura Bazzicalupo

    2012-11-01

    Full Text Available La psicoanalisi lacaniana può essere utilizzata per riflettere sul sottile e invisibile processo di rappresentazione simbolica, nel contesto della stereotipizzazione e della de-umanizzazione che troviamo in opera nello stile paranoico della politica (per esempio, nelle teorie del complotto. L’articolo evidenzia come la pretesa di immunizzazione auto-conservativa sia indispensabile nei processi di soggettivazione politica, ma può produrre un rovesciamento distruttivo. Nella identità comunitaria paranoica, la negatività è cancellata e il male, kakon, proiettato su un Altro persecutorio. L’ultima parte dell’articolo mette a fuoco il nesso tra paranoia e psicosi nelle forme di violenza gratuita, terrorismo e droga, nel sistema post-totalitario neoliberale. Solo l’assunzione del fantasma (che organizza il nostro sguardo sul mondo e il suo attraversamento, può aiutare ad aprire il circolo paranoico dell’identità.

  5. IL6 gene promoter polymorphisms and type 2 diabetes

    DEFF Research Database (Denmark)

    Huth, Cornelia; Heid, Iris M; Vollmert, Caren

    2006-01-01

    Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, -174G>C (rs1800795) and -573G>C (rs1800796), have been investigated for association with type...... 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on >20,000 participants from 21 published and unpublished studies. Collected data represent eight different...... countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 -174G>C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found...

  6. Il mondo sloveno nell'opera di Ippolito Nievo

    Directory of Open Access Journals (Sweden)

    Marija Pirjevec

    1991-12-01

    Full Text Available L'interesse per il mondo slavo, per la sua cultura, letteratura, soprattutto quella popolare, per la sua storia e il folclore, fa parte integrante della curiosita intellettuale dell'epoca preromantica e di quella romantica. Già Herder nel suo libro Ideen  zur  Philosophie der  Geschichte der  Menschheit sottolineò l'importanza e il ruolo degli Slavi, chiamati per la loro indole pacifica e mansueta ad interpretare le fondamentali esigenze dell' epoca nuova: quelle della fraterna collaborazione tra i popoli. Il periodo in cui Niewo nacque e crebbe nella consapevolezza sempre  più vigile della necessità d'impegno politico e civille, l'Europa andava scoprendo il ricco partimonio poetico e folcloristico de li Slavi, che era di vitale  importanza per l'ulteriore sviluppo delle loro attività letteraria.

  7. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ~40 and ~1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...... in muscle could account for the systemic changes. Skeletal muscle signaling increased after 1 h of rhIL-6 infusion, indicated by a fourfold increase in the phosphorylated signal transducer and activator of transcription (STAT) 3-to-STAT3 ratio, whereas no changes in phosphorylated AMP-activated protein...

  8. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ∼40 and ∼1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...... in muscle could account for the systemic changes. Skeletal muscle signaling increased after 1 h of rhIL-6 infusion, indicated by a fourfold increase in the phosphorylated signal transducer and activator of transcription (STAT) 3-to-STAT3 ratio, whereas no changes in phosphorylated AMP-activated protein...

  9. Il mondo dei quanti la fisica quantistica per tutti

    CERN Document Server

    Ford, Kenneth W

    2006-01-01

    L'autore spiega come le leggi che governano l'enormemente piccolo e l'enormemente rapido sfidino il senso comune e mettano alla prova l'intelletto al limite delle sue possibilità. Ford introduce alle grandi idee di una teoria - la fisica quantistica - che continua a rimanere misteriosa nonostante i numerosi successi: la granularità (la materia e alcune sue proprietà, come l'energia, sono "grumose"), il dualismo onda-particella, il principio di indeterminazione, la natura dei bosoni e dei fermioni, il principio di sovrapposizione e la non separabilità (il fatto che un atomo possa trovarsi simultaneamente in due o più stati di moto diversi).

  10. IL-17/Th17 pathway is activated in acne lesions.

    Directory of Open Access Journals (Sweden)

    Hanna-Leena Kelhälä

    Full Text Available The mechanisms of inflammation in acne are currently subject of intense investigation. This study focused on the activation of adaptive and innate immunity in clinically early visible inflamed acne lesions and was performed in two independent patient populations. Biopsies were collected from lesional and non-lesional skin of acne patients. Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed at the RNA and also protein level with real-time PCR (RT-PCR and Luminex technology. Cytokines involved in Th17 lineage differentiation (IL-1β, IL-6, TGF-β, IL23p19 were remarkably induced at the RNA level. In addition, proinflammatory cytokines and chemokines (TNF-α, IL-8, CSF2 and CCL20, Th1 markers (IL12p40, CXCR3, T-bet, IFN-γ, T regulatory cell markers (Foxp3, IL-10, TGF-β and IL-17 related antimicrobial peptides (S100A7, S100A9, lipocalin, hBD2, hBD3, hCAP18 were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL-17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway is activated and may play a pivotal role in the disease process, possibly offering new targets of therapy.

  11. IL-17/Th17 Pathway Is Activated in Acne Lesions

    Science.gov (United States)

    Kelhälä, Hanna-Leena; Palatsi, Riitta; Fyhrquist, Nanna; Lehtimäki, Sari; Väyrynen, Juha P.; Kallioinen, Matti; Kubin, Minna E.; Greco, Dario; Tasanen, Kaisa; Alenius, Harri; Bertino, Beatrice; Carlavan, Isabelle; Mehul, Bruno; Déret, Sophie; Reiniche, Pascale; Martel, Philippe; Marty, Carine; Blume-Peytavi, Ulrike; Voegel, Johannes J.; Lauerma, Antti

    2014-01-01

    The mechanisms of inflammation in acne are currently subject of intense investigation. This study focused on the activation of adaptive and innate immunity in clinically early visible inflamed acne lesions and was performed in two independent patient populations. Biopsies were collected from lesional and non-lesional skin of acne patients. Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed at the RNA and also protein level with real-time PCR (RT-PCR) and Luminex technology. Cytokines involved in Th17 lineage differentiation (IL-1β, IL-6, TGF-β, IL23p19) were remarkably induced at the RNA level. In addition, proinflammatory cytokines and chemokines (TNF-α, IL-8, CSF2 and CCL20), Th1 markers (IL12p40, CXCR3, T-bet, IFN-γ), T regulatory cell markers (Foxp3, IL-10, TGF-β) and IL-17 related antimicrobial peptides (S100A7, S100A9, lipocalin, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL-17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway is activated and may play a pivotal role in the disease process, possibly offering new targets of therapy. PMID:25153527

  12. IL12Rβ1ΔTM Is a Secreted Product of il12rb1 That Promotes Control of Extrapulmonary Tuberculosis

    Science.gov (United States)

    Ray, Aurelie A.; Fountain, Jeffrey J.; Miller, Halli E.; Cooper, Andrea M.

    2014-01-01

    IL12RB1 is a human gene that is important for resistance to Mycobacterium tuberculosis infection. IL12RB1 is expressed by multiple leukocyte lineages, and encodes a type I transmembrane protein (IL12Rβ1) that associates with IL12p40 and promotes the development of host-protective TH1cells. Recently, we observed that il12rb1—the mouse homolog of IL12RB1—is alternatively spliced by leukocytes to produce a second isoform (IL12Rβ1ΔTM) that has biological properties distinct from IL12Rβ1. Although the expression of IL12Rβ1ΔTM is elicited by M. tuberculosis in vivo, and its overexpression enhances IL12p40 responsiveness in vitro, the contribution of IL12Rβ1ΔTM to controlling M. tuberculosis infection has not been tested. Here, we demonstrate that IL12Rβ1ΔTM represents a secreted product of il12rb1 that, when absent from mice, compromises their ability to control M. tuberculosis infection in extrapulmonary organs. Furthermore, elevated M. tuberculosis burdens in IL12Rβ1ΔTM-deficient animals are associated with decreased lymph node cellularity and a decline in TH1 development. Collectively, these data support a model wherein IL12Rβ1ΔTM is a secreted product of il12rb1 that promotes resistance to M. tuberculosis infection by potentiating TH cells response to IL-12. PMID:25404030

  13. Variations in IL-23 and IL-25 receptor gene structure, sequence and expression associated with the two disease forms of sheep paratuberculosis.

    Science.gov (United States)

    Nicol, Louise; Gossner, Anton; Watkins, Craig; Chianini, Francesca; Dalziel, Robert; Hopkins, John

    2016-02-09

    The immunopathology of paucibacillary and multibacillary sheep paratuberculosis is characterized by inflammatory T cell and macrophage responses respectively. IL-23 and IL-25 are key to the development of these responses by interaction with their complex receptors, IL-23R/IL-12RB1 and IL-17RA/IL-17RB. In humans, variations in structure, sequence and/or expression of these genes have been implicated in the different pathological forms of tuberculosis and leprosy, and in gastrointestinal inflammatory disorders such as Crohn's disease. Sequencing has identified multiple transcript variants of sheep IL23R, IL12RB1 and IL17RB and a single IL17RA transcript. RT-qPCR assays were developed for all the identified variants and used to compare expression in the ileo-caecal lymph node of sheep with paucibacillary or multibacillary paratuberculosis and uninfected animals. With IL-23 receptor, only the IL12RB1v3 variant, which lacks the receptor activation motif was differentially expressed and was significantly increased in multibacillary disease; this may contribute to high Th2 responses. Of the IL17RB variants only full length IL17RB was differentially expressed and was significantly increased in multibacillary pathology; which may also contribute to Th2 polarization. IL17RA expression was significantly increased in paucibacillary disease. The contrast between the IL17RA and IL17RB results may indicate that, in addition to Th1 cells, Th17 T cells are also involved in paucibacillary pathology.

  14. Characterization of receptor-associated protein complex assembly in interleukin (IL)-2- and IL-15-activated T-cell lines

    DEFF Research Database (Denmark)

    Osinalde, Nerea; Sánchez-Quiles, Virginia; Akimov, Vyacheslav

    2017-01-01

    to their functional dichotomy. In this study, we aimed to decipher the receptor complex assembly in IL-2- and IL-15-activated T-lymphocytes that is highly orchestrated by site-specific phosphorylation events. Comparing the cytokine-induced interactome of the interleukin receptor beta and gamma subunits shared...

  15. Nasal IL-17F is related to bronchial IL-17F/neutrophilia and exacerbations in stable atopic severe asthma

    NARCIS (Netherlands)

    Sorbello, V; Ciprandi, G; Di Stefano, A; Massaglia, G M; Favatà, G; Conticello, S; Malerba, M; Folkerts, G; Profita, M; Rolla, G; Ricciardolo, F L M

    Severe asthma (SA) is associated with neutrophil recruitment and T helper (TH )17 chemokine overexpression in bronchial biopsies. We aimed to evaluate IL-17A and IL-17F expression in nasal/bronchial lamina propria of atopic mild-to-severe asthmatics and controls in relation to neutrophilia and

  16. Targeting IL-17 AND IL-17D receptors of rheumatoid arthritis using phytocompounds: A Molecular Docking study

    Science.gov (United States)

    Thabitha, A.; Thoufic Ali, A. M. Mohamed; Shweta Kumari, Singh; Rakhi; Swami, Varsha; Mohana Priya, A.; Sajitha Lulu, S.

    2017-11-01

    Rheumatoid arthritis (RA) is a chronic autoimmune condition of the connective tissue in synovial joints, characterized by inflammation which can lead to bone and cartilage destruction. IL-17 and IL-17D cytokines produced by a number of cell types, primarily promote pro-inflammatory immune responses and negative regulator in fibroblast growth factor signalling. Thus, the promising therapeutic strategies focus on targeting these cytokines, which has led to the identification of effective inhibitors. However, several studies focused on identifying the anti-arthritic potential of natural compounds. Therefore, in the present study we undertook in silico investigations to decipher the anti-inflammatory prospective of phytocompounds by targeting IL-17 and IL-17D cytokines using Patch Dock algorithm. Additionally, IL-17 and IL-17D proteins structure were modelled and validated for molecular docking study. Further, phytocompounds based on anti-inflammatory property were subjected to Lipinski filter and ADMET properties indicated that all of these compounds showed desirable drug-like criteria. The outcome of this investigation sheds light on the anti-inflammatory mechanism of phytocompounds by targeting IL-17 and IL-D for effective treatment of RA.

  17. TLR2 Elicits IL-17-Mediated RANKL Expression, IL-17, and OPG Production in Neutrophils from Arthritic Mice

    Directory of Open Access Journals (Sweden)

    Viktoriya Milanova

    2014-01-01

    Full Text Available We investigated the ability of neutrophils to express receptor activator of nuclear factor kappa-B ligand (RANKL, to secrete osteoprotegerin (OPG, and to produce IL-17. Arthritis was induced by intra-articular injection of zymosan, a ligand for Toll-like receptor 2 (TLR2. Frequencies of neutrophils in bone marrow (BM, blood and synovial fluid (SF, receptor expression, and cytokine production were evaluated by flow cytometry. 1A8 antibody (1A8 Ab was used to deplete neutrophils in zymosan-injected SCID mice. IL-17, RANKL, and OPG amounts in SF, serum, or cell cultures were determined by ELISA. The development of arthritis was associated with increased secretion of IL-17, RANKL, and OPG in serum and SF, elevated frequencies of Ly6G+CD11b+ cells in BM, blood, and SF and upregulated RANKL expression. Both IL-17 and OPG were absent in serum and SF after neutrophil depletion; therefore we assume that they were released by neutrophils. In vitro blood Ly6G+CD11b+ cells from arthritic mice produced spontaneously IL-17, IFN-γ, and OPG and expressed RANKL. This phenotype was sustained by IL-17. TLR2 engagement increased IL-17 and IFN-γ production, potentiated IL-17-mediated RANKL expression, and inhibited OPG secretion. We conclude that TLR2 regulates the destructive potential of neutrophils and its targeting might limit joint alterations in arthritis.

  18. IL-2 and IL-15 regulate CD8+ memory T-cell differentiation but are dispensable for protective recall responses.

    Science.gov (United States)

    Mathieu, Cédric; Beltra, Jean-Christophe; Charpentier, Tania; Bourbonnais, Sara; Di Santo, James P; Lamarre, Alain; Decaluwe, Hélène

    2015-12-01

    The ability to mount effective secondary responses is a cardinal feature of memory CD8(+) T cells. An understanding of the factors that regulate the generation and recall capacities of memory T cells remains to be ascertained. Several cues indicate that two highly related cytokines, IL-2 and IL-15, share redundant functions in this process. To establish their combined roles in memory CD8(+) T-cell development, maintenance, and secondary responses, we compared the outcome of adoptively transferred IL2Rβ(+/-) or IL2Rβ(-/-) CD8(+) T cells after an acute viral infection in mice. Our results demonstrate that both IL-2 and IL-15 signals condition the differentiation of primary and secondary short-lived effector cells by altering the transcriptional network governing lineage choices. These two cytokines also regulate the homeostasis of the memory T-cell pool, with effector memory CD8(+) T cells being the most sensitive to these two interleukins. Noticeably, the inability to respond to both cytokines limits the proliferation and survival of primary and secondary effectors cells, whereas it does not preclude potent cytotoxic functions and viral control either initially or upon rechallenge. Globally, these results indicate that lack of IL-2 and IL-15 signaling modulates the CD8(+) T-cell differentiation program but does not impede adequate effector functions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. The modulatory role of cytokines IL-4 and IL-17 in the functional activity of phagocytes in diabetic pregnant women.

    Science.gov (United States)

    Fagundes, Danny L G; França, Eduardo L; Gonzatti, Michelangelo B; Rugde, Marilza V C; Calderon, Iracema M P; Honorio-França, Adenilda C

    2018-01-01

    The study investigated the role of cytokines IL-4 and IL-17 in the modulation of the functional activity of mononuclear phagocytes in diabetic pregnant women with hyperglycemia. Sixty pregnant women were assigned to the following groups: nondiabetic (ND), mild gestational hyperglycemia (MGH), gestational diabetes mellitus (GDM), or type 2 diabetes mellitus (DM2). The functional activity of phagocytes from maternal blood, cord blood, and colostrum was assessed by determining their superoxide release, phagocytosis, microbicidal activity, and intracellular Ca 2+ release. Irrespective of glycemic status, colostrum and blood cells treated with IL-4 and IL-17 increased superoxide release in the presence of enteropathogenic Escherichia coli (EPEC). The highest phagocytosis rate was observed in cells from the DM2 group treated with IL-4. In all the groups, phagocytes from colostrum, maternal blood, and cord blood exhibited higher microbicidal activity against EPEC when treated with cytokines. IL-17 increased intracellular Ca 2+ release by colostrum phagocytes in diabetic groups. The results indicate that the IL-4 and IL-17 modulate the functional activity of phagocytes in the maternal blood, cord blood, and colostrum of diabetic mother. The natural immunity resulting from the interaction between the cells and cytokines tested may be an alternative procedure to improve the prognosis of maternal and newborn infections. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  20. Genetic deletion of IL-25 (IL-17E) confers resistance to dextran sulfate sodium-induced colitis in mice

    Science.gov (United States)

    IL-25 is emerging as a key regulator of inflammation in the intestinal mucosa because of its ability to promote Th2 while suppressing Th1 and Th17 cytokine responses. We investigated the contribution of endogenous IL-25 to DSS-induced colitis in mice. Mice were exposed to DSS in drinking water ad li...

  1. The association of novel IL-33 polymorphisms with sIL-33 and risk of systemic lupus erythematosus.

    Science.gov (United States)

    Guo, Jing; Xiang, Yang; Peng, You-Fan; Huang, Hua-Tuo; Lan, Yan; Wei, Ye-Sheng

    2016-09-01

    The serum level of IL-33 was upregulated in systemic lupus erythematosus (SLE), which may be used as biomarkers and/or therapeutic targets for SLE. The aim of this study was to investigate the association of four novel polymorphisms of IL-33 with risk of SLE. The study population comprised 540 Chinese individuals, including 257subjects with SLE and 283 healthy controls. The gene polymorphism was measured using Snapshot SNP genotyping assays and confirmed by sequencing. Serum IL-33 (sIL-33) levels were measured by ELISA. The serum SLE levels were significantly higher in the group of patients with SLE than those in the control group (Prisk of SLE as compared with the rs1891385 A allele (OR=1.405, 95% CI, 1.052-1.875, P=0.021). The C-T-T-G haplotype was significantly increased the risk of SLE (OR=1.411; 95% CI, 1.021-1.948; P=0.036). IL-33 gene rs1891385 polymorphism was significantly associated with the expression of sIL-33 in the SLE patients. Besides, in our study, we found that the unregulated sIL-33 level was significantly associated with the abnormal changed CRP and ESR. This is the first study reporting the IL-33 gene polymorphisms and SLE, which may help refine the SLE risk profile. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Intensive Cytokine induction in Pandemic H1N1 Influenza Virus Infection Accompanied by Robust Production of IL-10 and IL-6

    Science.gov (United States)

    Yu, Xuelian; Zhang, Xi; Zhao, Baihui; Wang, Jiayu; Zhu, Zhaokui; Teng, Zheng; Shao, Junjie; Shen, Jiaren; Gao, Ye; Yuan, Zhengan; Wu, Fan

    2011-01-01

    Background The innate immune system is the first line of defense against viruses by inducing expression of cytokines and chemokines. Many pandemic influenza H1N1 virus [P(H1N1)] infected severe cases occur in young adults under 18 years old who were rarely seriously affected by seasonal influenza. Results regarding host cytokine profiles of P(H1N1) are ambivalent. In the present study we investigated host cytokine profiles in P(H1N1) patients and identified cytokines related to disease severity. Methods and Principal Findings We retrieved 77, 59, 26 and 26 sera samples from P(H1N1) and non-flu influenza like illness (non-ILIs) cases with mild symptoms (mild patients), P(H1N1) vaccinees and healthy individuals, respectively. Nine and 16 sera were from hospitalized P(H1N1) and non-ILIs patients with severe symptoms (severe patients). Cytokines of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were assayed by cytokine bead array, IL-17 and IL-23 measured with ELISA. Mild P(H1N1) patients produced significantly elevated IL-2, IL-12, IFN-γ, IL-6, TNF-α, IL-5, IL-10, IL-17 and IL-23 versus to healthy controls. While an overwhelming IL-6 and IL-10 production were observed in severe P(H1N1) patients. Higher IL-10 secretion in P(H1N1) vaccinees confirmed our observation that highly increased level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression. Conclusion and Significance A comprehensive innate immune response was activated at the early stage of P(H1N1) infection with a combine Th1/Th2/Th3 cytokines production. As disease progression, a systemic production of IL-6 and IL-10 were observed in severe P(H1N1) patients. Further analysis found a strong correlation between IL-6 and IL-10 production in the severe P(H1N1) patients. IL-6 may be served as a mediator to induce IL-10 production. Highly elevated level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression, but the underlying mechanism awaits further

  3. Interleukin (IL)-1 in rat parturition: IL-1 receptors 1 and 2 and accessory proteins abundance in pregnant rat uterus at term - regulation by progesterone.

    Science.gov (United States)

    Ishiguro, Tomohito; Takeda, Jun; Fang, Xin; Bronson, Heather; Olson, David M

    2016-07-01

    The role of interleukin-1 (IL-1), a pro-inflammatory cytokine, in parturition is typically noted by changes in its concentrations. Studying the expression of its receptor family, IL-1 receptor (IL-1R) 1, IL-1R2, IL-1R accessory protein (IL-1RAcP), and its predominantly brain isoform, IL-1RAcPb, during late gestation in the uterus in the Long-Evans rat is another. We assessed changes in their mRNA and protein relative abundance in the uterus and compared IL-1RAcP and IL-1RAcPb mRNA abundance in uterus, cervix, ovaries, placenta, and whole blood of Long-Evans rats during late gestation or in RU486 and progesterone-treated dams using quantitative real-time PCR and western immunoblotting. IL-1R1, IL-1RAcP, and IL-1RAcPb mRNA abundance significantly increased in the uterus at delivery whereas IL-1R2 mRNA abundance significantly decreased. IL-1R1 protein increased at term and IL-1R2 protein decreased at term compared to nonpregnant uteri. IL1-RAcPb mRNA abundance was less than IL-1RAcP, but in the lower uterine segment it was the highest of all tissues examined. RU486 stimulated preterm delivery and an increase in IL-1R1 mRNA abundance whereas progesterone administration extended pregnancy and suppressed the increase in IL-1R1. These data suggest that changes in uterine sensitivity to IL-1 occur during late gestation and suggest another level of regulation for the control of delivery. The roles for IL-1RAcP and IL-1RAcPb need to be determined, but may relate to different intracellular signaling pathways. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  4. Aberrant intestinal microbiota due to IL-1 receptor antagonist deficiency promotes IL-17- and TLR4-dependent arthritis.

    Science.gov (United States)

    Rogier, Rebecca; Ederveen, Thomas H A; Boekhorst, Jos; Wopereis, Harm; Scher, Jose U; Manasson, Julia; Frambach, Sanne J C M; Knol, Jan; Garssen, Johan; van der Kraan, Peter M; Koenders, Marije I; van den Berg, Wim B; van Hijum, Sacha A F T; Abdollahi-Roodsaz, Shahla

    2017-06-23

    Perturbation of commensal intestinal microbiota has been associated with several autoimmune diseases. Mice deficient in interleukin-1 receptor antagonist (Il1rn -/- mice) spontaneously develop autoimmune arthritis and are susceptible to other autoimmune diseases such as psoriasis, diabetes, and encephalomyelitis; however, the mechanisms of increased susceptibility to these autoimmune phenotypes are poorly understood. We investigated the role of interleukin-1 receptor antagonist (IL-1Ra) in regulation of commensal intestinal microbiota, and assessed the involvement of microbiota subsets and innate and adaptive mucosal immune responses that underlie the development of spontaneous arthritis in Il1rn -/- mice. Using high-throughput 16S rRNA gene sequencing, we show that IL-1Ra critically maintains the diversity and regulates the composition of intestinal microbiota in mice. IL-1Ra deficiency reduced the intestinal microbial diversity and richness, and caused specific taxonomic alterations characterized by overrepresented Helicobacter and underrepresented Ruminococcus and Prevotella. Notably, the aberrant intestinal microbiota in IL1rn -/- mice specifically potentiated IL-17 production by intestinal lamina propria (LP) lymphocytes and skewed the LP T cell balance in favor of T helper 17 (Th17) cells, an effect transferable to WT mice by fecal microbiota. Importantly, LP Th17 cell expansion and the development of spontaneous autoimmune arthritis in IL1rn -/- mice were attenuated under germ-free condition. Selective antibiotic treatment revealed that tobramycin-induced alterations of commensal intestinal microbiota, i.e., reduced Helicobacter, Flexispira, Clostridium, and Dehalobacterium, suppressed arthritis in IL1rn -/- mice. The arthritis phenotype in IL1rn -/- mice was previously shown to depend on Toll-like receptor 4 (TLR4). Using the ablation of both IL-1Ra and TLR4, we here show that the aberrations in the IL1rn -/- microbiota are partly TLR4-dependent. We further

  5. La camorra e il caso Cirillo

    Directory of Open Access Journals (Sweden)

    A cura di Sarah Mazzenzana

    2016-11-01

    Full Text Available La sezione “Storia e Memoria” offre una selezione di brani tratti dal “Rapporto sulla Camorra” redatto dalla Commissione Parlamentare Antimafia nel 1993. Per la prima volta nella storia la Commissione rivolge la sua attenzione specificamente alla Camorra, fenomeno criminale fino a quel momento sottovalutato. Pubblichiamo qui la terza parte del rapporto, la quale offre uno spaccato degli eventi che hanno permesso la crescita imprenditoriale della Camorra: la ricostruzione delle aree colpite dal terremoto dell’Irpinia del 1980, l’ascesa della Nuova Camorra Organizzata di Raffaele Cutolo e infine il sequestro dell’allora assessore regionale ai lavori pubblici, Ciro Cirillo, episodio che sconvolse la politica e le istituzioni mettendone a nudo le complicità. Parole chiave: camorra; Commissione Parlamentare Antimafia; terremoto; sequestro Cirillo; imprenditoria The section “History and Memory” reports a selection of excerpts from the “Rapporto sulla Camorra”, issued by the Italian Parliamentary Anti-Mafia Commission in 1993. For the first time in its history, the Parliamentary Anti-Mafia Commission drew its attention specifically on a phenomenon which until that moment had been understimated. This document offers a significant  and thorough  understanding of the Camorra by dealing with the historical events that allowed the Campania criminal organisation’s entrepreneurial development, including the building reconstruction of the areas hit by the 1980 Irpinia earthquake , the growth of the Nuova Camorra Organizzata and the kidnapping of politician Ciro Cirillo.  Keywords: camorra; Italian Parliamentary Anti-mafia Commission; earthquake; Cirillo kidnapping; enterprise

  6. Il trasferimento lessicale: ambito italiano-francese.

    Directory of Open Access Journals (Sweden)

    Pia Galetto

    2009-12-01

    Full Text Available Normal 0 14 MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabella normale"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman";} Il contributo, incentrato sul tema dell’italianismo in prospettiva lessicografica tra storia, etimologia e cultura, tocca i problemi della durata del prestito italiano in francese, delle motivazioni che lo hanno generato, della funzione mediatrice che lo caratterizza, dell’estensione semantica in sincronia e diacronia e dell’aspetto derivazionale.  Normal 0 14 MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabella normale"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman";} The article focuses on Italianisms from a lexicographical perspective embracing history, etymology and culture and involving issues related to the duration of borrowings from Italian in French, the motives that generated it, the mediating function by which it is characterized, its semantic range, both synchronic and diachronic, and the aspect of derivations.   

  7. Il fantasma dell'universo che cos'è il neutrino

    CERN Document Server

    Votano, Lucia

    2015-01-01

    Ben prima della luce, a un decimillesimo di secondo dal Big Bang, i neutrini sono apparsi nell'universo. Dopo un secondo il brodo primordiale si era raffreddato abbastanza da consentire loro di muoversi liberi e ancora oggi, dopo quasi quattordici miliardi di anni, sono numerosissimi. Ma che cosa sono i neutrini? Elusivi come fantasmi, camaleontici, viaggiano indenni attraverso la materia arrivando dritti sino a noi dagli angoli più remoti e nascosti dell'universo. Per saperne di più seguiremo i fisici che li studiano in laboratori sotterranei o in luoghi estremi come i ghiacciai polari o le profondità marine.

  8. Il danese tranquillo Niels Bohr, un fisico e il suo tempo, 1885-1962

    CERN Document Server

    Pais, Abraham

    1993-01-01

    Niels Bohr è una figura centrale nella fisica del Novecento, padre fondatore della teoria atomica e della meccanica quantistica. La storia della sua vita, ricca e piena anche sul piano affettivo e personale, non può dunque ridursi a un resoconto dei suoi successi scientifici e Pais, allievo e poi amico di Bohr, ne è perfettamente consapevole. Il libro si sviluppa su vari piani: capitoli strettamente biografici o storico-scientifici si alternano a discussioni sulle idee di Bohr in campo politico e filosofico, sui suoi rapporti con Einstein, sul suo ruolo nei drammatici anni della guerra e su molti altri aspetti della vicenda umana.

  9. Dietary iron enhances colonic inflammation and IL-6/IL-11-Stat3 signaling promoting colonic tumor development in mice.

    Directory of Open Access Journals (Sweden)

    Anita C G Chua

    Full Text Available Chronic intestinal inflammation and high dietary iron are associated with colorectal cancer development. The role of Stat3 activation in iron-induced colonic inflammation and tumorigenesis was investigated in a mouse model of inflammation-associated colorectal cancer. Mice, fed either an iron-supplemented or control diet, were treated with azoxymethane and dextran sodium sulfate (DSS. Intestinal inflammation and tumor development were assessed by endoscopy and histology, gene expression by real-time PCR, Stat3 phosphorylation by immunoblot, cytokines by ELISA and apoptosis by TUNEL assay. Colonic inflammation was more severe in mice fed an iron-supplemented compared with a control diet one week post-DSS treatment, with enhanced colonic IL-6 and IL-11 release and Stat3 phosphorylation. Both IL-6 and ferritin, the iron storage protein, co-localized with macrophages suggesting iron may act directly on IL-6 producing-macrophages. Iron increased DSS-induced colonic epithelial cell proliferation and apoptosis consistent with enhanced mucosal damage. DSS-treated mice developed anemia that was not alleviated by dietary iron supplementation. Six weeks post-DSS treatment, iron-supplemented mice developed more and larger colonic tumors compared with control mice. Intratumoral IL-6 and IL-11 expression increased in DSS-treated mice and IL-6, and possibly IL-11, were enhanced by dietary iron. Gene expression of iron importers, divalent metal transporter 1 and transferrin receptor 1, increased and iron exporter, ferroportin, decreased in colonic tumors suggesting increased iron uptake. Dietary iron and colonic inflammation synergistically activated colonic IL-6/IL-11-Stat3 signaling promoting tumorigenesis. Oral iron therapy may be detrimental in inflammatory bowel disease since it may exacerbate colonic inflammation and increase colorectal cancer risk.

  10. Antibody blockade of IL-17 family cytokines in immunity to acute murine oral mucosal candidiasis.

    Science.gov (United States)

    Whibley, Natasha; Tritto, Elaine; Traggiai, Elisabetta; Kolbinger, Frank; Moulin, Pierre; Brees, Dominique; Coleman, Bianca M; Mamo, Anna J; Garg, Abhishek V; Jaycox, Jillian R; Siebenlist, Ulrich; Kammüller, Michael; Gaffen, Sarah L

    2016-06-01

    Antibodies targeting IL-17A or its receptor, IL-17RA, are approved to treat psoriasis and are being evaluated for other autoimmune conditions. Conversely, IL-17 signaling is critical for immunity to opportunistic mucosal infections caused by the commensal fungus Candida albicans, as mice and humans lacking the IL-17R experience chronic mucosal candidiasis. IL-17A, IL-17F, and IL-17AF bind the IL-17RA-IL-17RC heterodimeric complex and deliver qualitatively similar signals through the adaptor Act1. Here, we used a mouse model of acute oropharyngeal candidiasis to assess the impact of blocking IL-17 family cytokines compared with specific IL-17 cytokine gene knockout mice. Anti-IL-17A antibodies, which neutralize IL-17A and IL-17AF, caused elevated oral fungal loads, whereas anti-IL-17AF and anti-IL-17F antibodies did not. Notably, there was a cooperative effect of blocking IL-17A, IL-17AF, and IL-17F together. Termination of anti-IL-17A treatment was associated with rapid C. albicans clearance. IL-17F-deficient mice were fully resistant to oropharyngeal candidiasis, consistent with antibody blockade. However, IL-17A-deficient mice had lower fungal burdens than anti-IL-17A-treated mice. Act1-deficient mice were much more susceptible to oropharyngeal candidiasis than anti-IL-17A antibody-treated mice, yet anti-IL-17A and anti-IL-17RA treatment caused equivalent susceptibilities. Based on microarray analyses of the oral mucosa during infection, only a limited number of genes were associated with oropharyngeal candidiasis susceptibility. In sum, we conclude that IL-17A is the main cytokine mediator of immunity in murine oropharyngeal candidiasis, but a cooperative relationship among IL-17A, IL-17AF, and IL-17F exists in vivo. Susceptibility displays the following hierarchy: IL-17RA- or Act1-deficiency > anti-IL-17A + anti-IL-17F antibodies > anti-IL-17A or anti-IL-17RA antibodies > IL-17A deficiency. © Society for Leukocyte Biology.

  11. Functional IL18 polymorphism and susceptibility to Chronic Chagas Disease.

    Science.gov (United States)

    Nogueira, Luciana Gabriel; Frade, Amanda Farage; Ianni, Barbara Maria; Laugier, Laurie; Pissetti, Cristina Wide; Cabantous, Sandrine; Baron, Monique; Peixoto, Gisele de Lima; Borges, Ariana de Melo; Donadi, Eduardo; Marin-Neto, José A; Schmidt, André; Dias, Fabrício; Saba, Bruno; Wang, Hui-Tzu Lin; Fragata, Abilio; Sampaio, Marcelo; Hirata, Mario Hiroyuki; Buck, Paula; Mady, Charles; Martinelli, Martino; Lensi, Mariana; Siqueira, Sergio Freitas; Pereira, Alexandre Costa; Rodrigues, Virmondes; Kalil, Jorge; Chevillard, Christophe; Cunha-Neto, Edecio

    2015-05-01

    Chronic Chagas Disease cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi, the rest of the infected subjects remaining asymptomatic (ASY). The Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis. Local expression of IL-18 in CCC myocardial tissue has recently been described. IL-18 could potentially amplify the process by inducing increased expression of IFN-γ which in turn can increase the production of IL-18, thereby creating a positive feedback mechanism. In order to assess the contribution of the IL-18 to susceptibility to Chronic Chagas Disease, we investigated the association between a single nucleotide polymorphism (SNP) located in the IL-18 gene with the risk of developing Chagas cardiomyopathy. We analyzed the rs2043055 marker in the IL18 gene in a cohort of Chagas disease cardiomyopathy patients (n=849) and asymptomatic subjects (n=202). We found a significant difference in genotype frequencies among moderate and severe CCC patients with ventricular dysfunction. Our analysis suggests that the IL18 rs2043055 polymorphism- or a SNP in tight linkage disequilibrium with it- may contribute to modulating the Chagas cardiomyopathy outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Locoregional IL-2 low dose applications for gastrointestinal tumors

    Science.gov (United States)

    Krastev, Zachary; Koltchakov, V; Tomova, R; Deredjian, S; Alexiev, A; Popov, D; Tomov, B; Koten, Jan-Willem; Jacobs, John; Otter, Willem Den

    2005-01-01

    AIM: To explore the feasibility of local interleukin 2 (IL-2) in patients with different forms of abdominal cancer. This required experimentation with the time interval between IL-2 applications and the methods of application. METHODS: Sixteen patients with stages III and IV of gastrointestinal malignancies (primary or metastatic) who were admitted to our Department of Gastroenterology were treated with locoregionally applied IL-2 in low doses. RESULTS: No major problems applying locoregional IL-2 were encountered. In 6 out of 16 patients, a modest but clinically worthwhile improvement was obtained. Adverse effects were minimal. The therapeutic scheme was well tolerated, even in patients in a poor condition. CONCLUSION: This study demonstrates the feasibility of low dose locoregional IL-2 application in advanced abdominal cancer. Local IL-2 therapy gives only negligible adverse effects. The results suggest that it is important to apply intratumorally. Local IL-2 may be given adjunct to standard therapeutic regimes and does not imply complex surgical interventions. These initial results are encouraging. PMID:16222748

  13. Evolutionary Insights into IL17A in Lagomorphs.

    Science.gov (United States)

    Neves, Fabiana; Abrantes, Joana; Almeida, Tereza; Costa, Paulo P; Esteves, Pedro J

    2015-01-01

    In leporids, IL17A had been implicated in the host defense against extracellular pathogens, such as Francisella tularensis that infects hares and rabbits and causes the zoonotic disease tularemia. Here, we studied IL17A from five lagomorphs, European rabbit, pygmy rabbit, brush rabbit, European brown hare, and American pika. We observed that this protein is highly conserved between these species, with a similarity of 97-99% in leporids and ~88% between leporids and American pika. The exon/intron structure, N-glycosylation sites, and cysteine residues are conserved between lagomorphs. However, at codon 88, one of the interaction sites between IL17A and its receptor IL17RA, there is an Arg>Pro mutation that only occurs in European rabbit and European brown hare. This could induce critical alterations in the IL17A structure and conformation and consequently modify its function. The differences observed between leporids and humans or rodents might also represent important alterations in protein structure and function. In addition, as for other interleukins, IL17A sequences of human and European rabbit are more closely related than the sequences of human and mouse or European rabbit and mouse. This study gives further support to the hypothesis that European rabbit might be a more suitable animal model for studies on human IL17.

  14. Evolutionary Insights into IL17A in Lagomorphs

    Directory of Open Access Journals (Sweden)

    Fabiana Neves

    2015-01-01

    Full Text Available In leporids, IL17A had been implicated in the host defense against extracellular pathogens, such as Francisella tularensis that infects hares and rabbits and causes the zoonotic disease tularemia. Here, we studied IL17A from five lagomorphs, European rabbit, pygmy rabbit, brush rabbit, European brown hare, and American pika. We observed that this protein is highly conserved between these species, with a similarity of 97–99% in leporids and ~88% between leporids and American pika. The exon/intron structure, N-glycosylation sites, and cysteine residues are conserved between lagomorphs. However, at codon 88, one of the interaction sites between IL17A and its receptor IL17RA, there is an Arg>Pro mutation that only occurs in European rabbit and European brown hare. This could induce critical alterations in the IL17A structure and conformation and consequently modify its function. The differences observed between leporids and humans or rodents might also represent important alterations in protein structure and function. In addition, as for other interleukins, IL17A sequences of human and European rabbit are more closely related than the sequences of human and mouse or European rabbit and mouse. This study gives further support to the hypothesis that European rabbit might be a more suitable animal model for studies on human IL17.

  15. IL-1RN gene polymorphism is associated with peri-implantitis

    NARCIS (Netherlands)

    Laine, Marja L.; Leonhardt, Asa; Roos-Jansaker, Ann-Marie; Salvador Pena, A.; van Winkelhoff, Arie Jan; Winkel, Edwin G.; Renvert, Stefan

    Objectives: Interleukin (IL)-1 alpha, IL-1 beta and their natural specific inhibitor IL-1 receptor antagonist (IL-1ra) play a key role in the regulation of the inflammatory response in periodontal tissues. Polymorphisms in the IL-1 gene cluster have been associated with severe adult periodontitis.

  16. TNF-α blockade induces IL-10 expression in human CD4+ T cells

    NARCIS (Netherlands)

    Evans, Hayley G.; Roostalu, Urmas; Walter, Gina J.; Gullick, Nicola J.; Frederiksen, Klaus S.; Roberts, Ceri A.; Sumner, Jonathan; Baeten, Dominique L.; Gerwien, Jens G.; Cope, Andrew P.; Geissmann, Frederic; Kirkham, Bruce W.; Taams, Leonie S.

    2014-01-01

    IL-17+ CD4+ T (Th17) cells contribute to the pathogenesis of several human inflammatory diseases. Here we demonstrate that TNF inhibitor (TNFi) drugs induce the anti-inflammatory cytokine IL-10 in CD4+ T cells including IL-17+ CD4+ T cells. TNFi-mediated induction of IL-10 in IL-17+ CD4+ T cells is

  17. IL-1Ra (recombinant human IL-1 receptor antagonist in the treatment of rheumatoid arthritis: the efficacy

    Directory of Open Access Journals (Sweden)

    L. Cozzi

    2011-09-01

    Full Text Available Interleukin 1 receptor antagonist (IL-1Ra is a naturally occurring IL-1 inhibitor, acting as a “receptor antagonist”, which blocks IL-1 mediated signal transduction. In 1990 IL-1Ra was cloned and later on, a large numbers of studies led to disclosure of the crucial importance of the imbalance between IL-1 and IL-1Ra in the pathogenesis of rheumatoid arthritis (RA. In 1991, almost 8 years after the initial isolation of IL-1, recombinant IL-1Ra (IL-1ra, Kineret was introduced in clinical trials involving patients with RA. Between 2001 and 2002 IL-1ra was approved by the US Food and Drug Administration and by the European Agency for the Evaluation of the Medicinal Products and in 2003 it was registered in Italy, too. In RA recombinant IL-1ra has been evaluated in 5 randomized, placebo-controlled clinical trials involving more than 2900 patients. Two of the trials involved the use of IL-1ra as monotherapy versus placebo and two trials in combination with methotrexate (MTX; the last trial explored the use of a fixed 100 mg/day IL-1ra dosage in a RA patient population including a wide array of co-morbid conditions as well as concomitant medications. The studies confirmed both the efficacy and the safety of IL-1ra in patients with active and severe RA. 43% of patients receiving 150 mg/day IL-1ra achieved a 20% response according to the American College of Rheumatology criteria (ACR20, compared to 27% in the placebo group. In the MTX combination therapy study, 42% of the patients receiving 1 mg/Kg/day of IL-1ra achieved an ACR20, 24% an ACR50 and 10% an ACR70. In each study, significant improvements in the Health Assessment Questionnaire scores (HAQ were observed. There were rapid gains in the number of days at work or domestic activity in the treated patients, and the increases in productivity were dose related. At early 24 weeks, there was significant reduction of both the score for progression of joint space narrowing (JSN and the Total modified

  18. Il1-β involvement in cognitive impairment after sepsis.

    Science.gov (United States)

    Mina, Francielle; Comim, Clarissa M; Dominguini, Diogo; Cassol, Omar J; Dall Igna, Dhébora M; Ferreira, Gabriela K; Silva, Milena C; Galant, Leticia S; Streck, Emílio L; Quevedo, João; Dal-Pizzol, Felipe

    2014-04-01

    Sepsis is defined as the host's reaction to infection and characterised by a systemic inflammatory response with important clinical implications. Central nervous system dysfunction secondary to sepsis is associated with local generation of pro- and anti-inflammatory cytokines, impaired cerebral microcirculation, an imbalance of neurotransmitters, apoptosis and cognitive impairment. It's known that the IL-1β is one of the first cytokines to be altered. Thus, the objective of this study was to evaluate the role of IL-1β in cognitive parameters in brain tissue through the use of an IL-1β (IL-1ra) receptor antagonist up to 10 days and to assess blood-brain barrier permeability, cytokine levels, oxidative parameters and energetic metabolism up to 24 h, after sepsis induction. To this aim, we used sham-operated Wistar rats or submitted to the cecal ligation and perforation (CLP) procedure. Immediately after, the animals received one dose of 10 μg of IL-1ra. After 24 h, the rats were killed and were evaluated for biochemical parameters in the pre-frontal cortex, hippocampus and striatum. After 10 days, the animals were submitted to the habituation to the open field and step-down inhibitory avoidance task. We observed that the use of IL-1ra reverted the increase of blood-brain barrier permeability in the pre-frontal cortex, hippocampus and striatum; the increase of IL-1β, IL1-6 and TNF-α levels in the pre-frontal cortex and striatum; the decrease of complex I activity in the pre-frontal, hippocampus and striatum; the increase of oxidative parameters in pre-frontal cortex, hippocampus and striatum; and cognitive impairment. In conclusion, the results observed in this study reinforce the role of acute brain inflammatory response, in particular, the IL1β response, in the cognitive impairment associated with sepsis.

  19. IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP.

    Directory of Open Access Journals (Sweden)

    Stephen F Murphy

    Full Text Available Chronic pelvic pain syndrome (CPPS is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.

  20. Modulation of CD4+and CD8+T Cell Function and Cytokine Responses in Strongyloides stercoralis Infection by Interleukin-27 (IL-27) and IL-37.

    Science.gov (United States)

    Anuradha, Rajamanickam; Munisankar, Saravanan; Bhootra, Yukthi; Dolla, Chandrakumar; Kumaran, Paul; Nutman, Thomas B; Babu, Subash

    2017-11-01

    Strongyloides stercoralis infection is associated with diminished antigen-specific Th1- and Th17-associated responses and enhanced Th2-associated responses. Interleukin-27 (IL-27) and IL-37 are two known anti-inflammatory cytokines that are highly expressed in S. stercoralis infection. We therefore wanted to examine the role of IL-27 and IL-37 in regulating CD4 + and CD8 + T cell responses in S. stercoralis infection. To this end, we examined the frequency of Th1/Tc1, Th2/Tc2, Th9/Tc9, Th17/Tc17, and Th22/Tc22 cells in 15 S. stercoralis -infected individuals and 10 uninfected individuals stimulated with parasite antigen following IL-27 or IL-37 neutralization. We also examined the production of prototypical type 1, type 2, type 9, type 17, and type 22 cytokines in the whole-blood supernatants. Our data reveal that IL-27 or IL-37 neutralization resulted in significantly enhanced frequencies of Th1/Tc1, Th2/Tc2, Th17/Tc17, Th9, and Th22 cells with parasite antigen stimulation. There was no induction of any T cell response in uninfected individuals following parasite antigen stimulation and IL-27 or IL-37 neutralization. Moreover, we also observed increased production of gamma interferon (IFN-γ), IL-5, IL-9, IL-17, and IL-22 and decreased production of IL-10 following IL-27 and IL-37 neutralization and parasite antigen stimulation in whole-blood cultures. Thus, we demonstrate that IL-27 and IL-37 limit the induction of particular T cell subsets along with cytokine responses in S. stercoralis infections, which suggest the importance of IL-27 and IL-37 in immune modulation in a chronic helminth infection. Copyright © 2017 American Society for Microbiology.

  1. Conoscere il patrimonio architettonico: il DARDUS dell’Università Politecnica delle Marche

    Directory of Open Access Journals (Sweden)

    Eva Savina Malinverni

    2007-03-01

    Full Text Available E’ in questa ottica che all’interno del Dipartimento collaborano docenti e ricercatori di vari settori scientificodisciplinari. Nella panoramica che viene qui presentata verrà posto l’accento maggiormente su due filoni di attività che sono anche più inerenti al contesto divulgativo di GEOmedia: il rilievo ed i sistemi informativi. Tematiche sulle quali il gruppo di ricerca del DARDUS ha avviato varie iniziative che verranno di seguito illustrate. Le dinamiche di collaborazione e di ricerca inerenti i temi del rilievo e della documentazione in banche datigeoreferenziate sviluppate nelle sale del Dipartimento riguardano non solo l’ambito architettonico ma anche quello ambientale. Queste attività sono svolte all’interno di laboratori debitamente attrezzati, nei quali docenti, ricercatori e tecnici istruiscono dottorandi, laureandi etirocinanti in stretta collaborazione e produttiva sinergia portando a sviluppare e collaudare nuove procedure e sistemi integrati di acquisizione e gestione dei dati raccoltinella varie esperienze di studio.

  2. Release of IL-1β via IL-1β-Converting Enzyme in a Skin Dendritic Cell Line Exposed to 2,4-Dinitrofluorobenzene

    Directory of Open Access Journals (Sweden)

    Teresa J. Matos

    2005-01-01

    increased IL-1β receptor immunoreactivity. The rapid effect of DNFB on the release of mature IL-1β, without inducing an increase of IL-1β mRNA in FSDC, suggests a posttranslational modification of pro-IL-1β by ICE activity.

  3. IL-33-induced alterations in murine intestinal function and cytokine responses are MyD88, STAT6, and IL-13-dependent

    Science.gov (United States)

    IL-33 is a recently identified cytokine member of the IL-1 family. The biological activities of IL-33 are associated with promotion of Th2 and inhibition of Th1/Th17 immune responses. Exogenous IL-33 induces a typical “type 2” immune response in the gastrointestinal tract, yet the underlying mechani...

  4. Polymorphisms of ST2-IL18R1-IL18RAP gene cluster: a new risk for autoimmune thyroid diseases.

    Science.gov (United States)

    Wang, X; Zhu, Y F; Li, D M; Qin, Q; Wang, Q; Muhali, F S; Jiang, W J; Zhang, J A

    2016-02-01

    Interleukin 33 (IL33) / ST2 pathway and ST2-interlukin18 receptor1-interlukin18 receptor accessory protein (ST2-IL18R1-IL18RAP) gene cluster have been involved in many autoimmune diseases but few report in autoimmune thyroid diseases (AITD). In this study, we investigated whether polymorphisms of IL33, ST2, IL18R1, and IL18RAP are associated with Graves' disease (GD) and Hashimoto's thyroiditis (HT), two major forms of AITD, among a Chinese population. A total of 11 SNPs were explored in a case-control study including 417 patients with GD, 250 HT patients and 301 controls, including rs1929992, rs10975519, rs10208293, rs6543116, rs1041973, rs3732127, rs11465597, rs1035130, rs2293225, rs1035127, rs917997 of IL 33, ST2-IL18R1-IL18RAP gene cluster. Genotyping of these SNPs was performed using matrix-assisted laser desorption / ionization-time-of-flight mass spectrometer (MALDI-TOF-MS) platform from Sequenom. The frequencies of allele A and AA+AG genotype of rs6543116 (ST2) in HT patients were significantly increased compared with those of the controls (P = 0.029/0.021, OR = 1.31/1.62). And in another SNP rs917997, AA+AG genotype presented an increased frequency in HT subjects compared with controls (P = 0.046, OR = 1.53). Furthermore, the haplotype GAGCCCG from ST2-IL18R1-IL18RAP gene cluster (rs6543116, rs1041973, rs1035130, rs3732127, rs1035127, rs2293225, rs917997) was associated with increased susceptibility to GD with an OR of 2.03 (P = 0.022, 95% CI = 1.07-3.86). Some SNPs of ST2-IL18R1-IL18RAP gene cluster might increase the risk of susceptibility of HT and GD in Chinese Han population. © 2015 John Wiley & Sons Ltd.

  5. Il monastero di Bobbio in età altomedievale

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    Eleonora Destefanis

    2003-11-01

    Full Text Available Il monastero di Bobbio, sorto sull’Appennino piacentino per iniziativa di S. Colombano e con il sostegno del re longobardo Agilulfo, ha conosciuto una lunga storia di studi che ne hanno messo di volta in volta in luce l’importanza come centro scrittorio e di raccolta di testi, il ruolo di primo piano quale interlocutore delle monarchie avvicendatesi nel corso dell’altomedioevo, la posizione di spicco nell’esperienza del monachesimo insulare sul Continente, riflessa da una cospicua produzione ...

  6. Gene variation in IL-7 receptor (IL-7R)α affects IL-7R response in CD4+ T cells in HIV-infected individuals

    DEFF Research Database (Denmark)

    Hartling, Hans Jakob; Ryder, Lars P.; Ullum, Henrik

    2017-01-01

    Optimal CD4+ T cell recovery after initiating combination antiretroviral treatment (cART) in HIV infection reduces risk of morbidity and mortality. T-allele homozygosity (‘TT’) in the single nucleotide polymorphism, rs6897932(C/T), in the IL-7 receptor α (IL-7RA) is associated with faster CD4+ T...... cell recovery after cART initiation compared to C-allele homozygosity in rs6897932 (‘CC’). However, underlying mechanisms are unknown. We aimed to examine potential mechanisms explaining the association between rs6897932 and CD4+ T cell recovery. Ten ‘TT’ and 10 ‘CC’ HIV-infected individuals matched...... on gender, age, and nadir and current CD4+ T cell counts were included in a cross-sectional study. ‘TT’ individuals had higher proportion of CD4+ T cells expressing pSTAT5 compared to ‘CC’ individuals after stimulating with IL-7, especially when co-stimulated with soluble IL7-RA (sIL-7RA). Furthermore, ‘TT...

  7. Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice

    DEFF Research Database (Denmark)

    Gavito, Ana Luisa; Bautista, Dolores; Suarez, Juan

    2016-01-01

    High-fat diet-induced obesity (DIO) is associated with fatty liver and elevated IL-6 circulating levels. IL-6 administration in rodents has yielded contradictory results regarding its effects on steatosis progression. In some models of fatty liver disease, high doses of human IL-6 ameliorate...... the liver steatosis, whereas restoration of IL-6 in DIO IL-6-/- mice up-regulates hepatic lipogenic enzymes and aggravates steatosis. We further examined the effects of chronic low doses of murine IL-6 on hepatic lipid metabolism in WT mice in DIO. IL-6 was delivered twice daily in C57BL/6J DIO mice for 15...

  8. High IL-17E and low IL-17C dermal expression identifies a fibrosis-specific motif common to morphea and systemic sclerosis.

    Directory of Open Access Journals (Sweden)

    Paola Adele Lonati

    Full Text Available BACKGROUND: High interleukin (IL-17A levels are characteristically found in the skin of systemic sclerosis (SSc individuals. Our aim was to investigate whether the dermal expression of IL-17A and related IL-17 family members (i.e. IL-17C, IL-17E and IL-17F could distinguish fibrotic from healthy skin and could show similarities in SSc and morphea, two disorders with presumed distinct pathogenesis, but characterized by skin fibrosis. METHODS: Biopsies were obtained from the involved skin of 14 SSc, 5 morphea and 8 healthy donors (HD undergoing plastic surgery. Immunohistochemistry/immunofluorescence techniques were coupled to a semi-automated imaging quantification approach to determine the presence of the IL-17 family members in the skin. The in vitro effects induced by the IL-17 family members on fibroblasts from normal and SSc individuals were assessed by ELISA and RIA. RESULTS: Positive cells for each of the IL-17 isoforms investigated were present in the dermis of all the individuals tested, though with variable frequencies. SSc individuals had increased frequency of IL-17A+ (p = 0.0237 and decreased frequency of IL-17F+ (p = 0.0127 and IL-17C+ cells (p = 0.0008 when compared to HD. Similarly, morphea individuals had less frequent IL-17C+ cells (p = 0.0186 in their skin but showed similar number of IL-17A+ and IL-17F+ cells when compared to HD. Finally, IL-17E+ cells were more numerous in morphea (p = 0.0109 and tended to be more frequent in SSc than in HD. Fibroblast production of IL-6, MMP-1 and MCP-1 was enhanced in a dose-dependent manner in the presence of IL-17E and IL-17F, but not in the presence of IL-17C. None of the cytokine tested had significant effect on type I collagen production. Of interest, in SSc the frequency of both IL-17A and IL-17F positive cells increased with disease duration. CONCLUSIONS: The frequency of IL-17A and IL-17F distinguish SSc to morphea individuals while dermal expression of IL-17C (low and IL-17E (high

  9. Quando la fiction produce turismo. Due località per il cinema fantasy a confronto / When fiction produces tourism. Two localities for fantasy cinema in comparison

    Directory of Open Access Journals (Sweden)

    Antonio Violante

    2016-05-01

    Full Text Available Dubrovnik, capitale del mondo medioevale fantasy della serie televisiva Game of Thrones, in cui essa è ambientata, è stata sottoposta a una “invasione” turistica non tanto per i suoi pregi in sé, quanto perché le sue strutture fungono da scenario alla fiction, da diventare proprio per questo meritevoli di visita. Si sono organizzati tour alla visita dei luoghi del set, con tanto di merchandising connesso.L’interesse verso gli ksour tunisini utilizzati nelle riprese dei film componenti la saga fantascientifica di Star Wars, ha prodotto un altro caso di turismo cinematografico. Infatti, Star Wars ha inciso profondamente sull’immagine turistica della Tunisia, anche ad anni di distanza dalle riprese colà avvenute.     Il metodo comparativo di indagine su queste località, condotta sulla base della documentazione esistente e di una ricognizione dei luoghi, ha mirato a porre in evidenza le contraddizioni in cui esse sono incorse; infatti, da centri celebri per i loro pregi artistici e architettonici, sono diventate poli di attrazione turistica in quanto  scenari per fiction di successo.   Dubrovnik – the capital of the Medieval fantasy world of the tv show Game of Thrones – has been “invaded” by tourists not just because its own merits, but especially because it is the scenary of the tv fiction and therefore worthy of visiting. There have been tours to set locations and all the connected merchandising. The interest towards the Tunisian ksour used during shooting of the movies within the sci-fi saga Star Wars produced another case of cinema tourism. In fact, Star Wars made a profound impact on Tunisia’s touristic image, despite all the years that have passed since the making of the movie.The comparative method used to analyse these localities, based on existing documentation and first-hand visits aims to highlight the contradictions noticed: in fact, instead of being famous for their artistic and architectural values, they

  10. Clinical significance of measurement of plasma leptin and serum IL-6, IL-18 levels after treatment in patients with children nephrotic syndrome

    International Nuclear Information System (INIS)

    Wang Xiaoyan

    2011-01-01

    Objective: To explore the clinical significance of changes of plasma leptin and serum IL-6, IL-18 levels after treatment in patients with children nephrotic syndrome. Methods: Plasma leptin (with RIA) serum IL-6, IL-18 (with ELISA) levels were measured in 31 patients with children nephrotic syndrome both before and after treatment as well as in 30 controls. Results: Before treatment,the plasma leptin and serum IL-6, IL-18 levels were significantly higher than those in controls(P <0.01). After treatment for 3 months, the levels in patients though dropped markedly remained significantly higher than those in controls (P<0.05). Plasma leptin levels were positively correlated with IL-6, IL-18 levels (r=0.6138, 0.5784, P<0.01). Conclusion: Changes of plasma leptin and serum IL-6, IL-18 levels after treatment might be of prognostic importance in patients with children nephrotic syndrome. (authors)

  11. Positive affective style covaries with stimulated IL-6 and IL-10 production in a middle-aged community sample.

    Science.gov (United States)

    Prather, Aric A; Marsland, Anna L; Muldoon, Matthew F; Manuck, Stephen B

    2007-11-01

    An emerging literature indicates that dispositional positive affect (PA) may play a protective role in health and render individuals less susceptible to inflammatory diseases. In this regard, it has been suggested that PA is associated with diminished activation of innate immune pathways. To explore this possibility, we examined relationships between trait positive emotional style, as assessed by the Positive and Negative Affect Schedule, and monocyte-derived lipopolysaccharide-induced production of the pro- and anti-inflammatory cytokines, interleukin (IL)-6, IL-1beta, TNF-alpha, and IL-10, among 146 healthy adults aged 30-54. After controlling for demographic factors and other covariates (age, gender, race, body mass index and white blood cell count), hierarchical regression analyses revealed an inverse association between trait PA and stimulated production of IL-6 (DeltaR(2)=.03, b=-.18, p stimulated IL-1beta or TNF-alpha. Additionally, trait negative affect was unrelated to any of the stimulated cytokine levels. These initial findings suggest that individuals higher in trait positive emotional style show decreased in vitro production of the early inflammatory mediators IL-6 and IL-10 in response to stimulation with endotoxin which may confer protection against the emergence and progression of inflammatory diseases. Further exploration of this potential psychophysiological pathway is warranted.

  12. IL-12 and IL-18 induction and subsequent NKT activation effects of the Japanese botanical medicine Juzentaihoto.

    Science.gov (United States)

    Fujiki, Kazuhiko; Nakamura, Masanori; Matsuda, Takako; Isogai, Mariko; Ikeda, Minako; Yamamoto, Yutaka; Kitamura, Mari; Sazaki, Naoko; Yakushiji, Fumiatsu; Suzuki, Shinji; Tomiyama, Junji; Uchida, Takashi; Taniguchi, Ken

    2008-06-01

    In this study, we first measured some cytokine concentrations in the serum of patients treated with Juzentaihoto (JTT). Of the cytokines measured interleukin (IL) -18 was the most prominently up-regulated cytokine in the serum of patients under long term JTT administration. We next evaluated the effects of JTT in mice, focusing especially on natural killer T (NKT) cell induction. Mice fed JTT were compared to control group ones. After sacrifice, the liver was fixed, embedded and stained. Transmission electron microscope (TEM) observations were performed. Although the mice receiving the herbal medicine had same appearance, their livers were infiltrated with massive mononuclear cells, some of which were aggregated to form clusters. Immunohistochemical staining revealed that there was abundant cytokine expression of IL-12 and IL-18 in the liver of JTT treated mice. To clarify what the key molecules that induce immunological restoration with JTT might be, we next examined in vitro lymphocyte cultures. Mononuclear cells isolated and prepared from healthy volunteers were cultured with and without JTT. Within 24 hours, JTT induced the IL-12 and IL-18 production and later (72 hours) induction of interferon (IFN)-gamma. Oral administration of JTT may induce the expression of IL-12 in the early stage, and IL-18 in the chronic stage, followed by NKT induction. Their activation, following immunological restoration could contribute to anti-tumor effects.

  13. Closely related glycosylation patterns of recombinant human IL-2 expressed in a CHO cell line and natural IL-2

    International Nuclear Information System (INIS)

    Vita, N.; Magazin, M.; Marchese, E.; Lupker, J.; Ferrara, P.

    1990-01-01

    We report here the study of the glycosylation pattern of human recombinant (r) IL2 expressed in a Chinese hamster ovary (CHO) cell line. The human rIL2 secreted by this high-producing recombinant CHO cell line was metabolically radiolabelled with [35S]-methionine, or with [3H]-glucosamine and [3H]-galactose, purified to homogeneity, and then characterized. The electrophoretic analysis of the [35S]-methionine-labelled proteins present in the culture medium of the CHO cell line showed that the rIL2 represents approximately 12% of the total secreted proteins. Furthermore, pulse-chase experiments showed that the glycosylated rIL2 is synthesized and secreted within 30 min. The point of attachment and the structure of the carbohydrate moiety of the rIL2 was determined by: amino-terminal sequencing and fingerprint analysis of the 3H-labelled rIL2, mass spectroscopy of the amino-terminal tryptic octapeptide, and carbohydrate analysis after enzymatic (Vibrio cholerae neuraminidase and Aspergillus oryzae beta-galactosidase) or sulfuric acid hydrolysis. The results indicate that the recombinant protein possesses a sugar moiety O-linked to the threonine residue at position 3 of the polypeptide chain, and that sialic acid, galactose and N-acetyl galactosamine are components of this carbohydrate moiety. Taken together these results suggest that the recombinant molecule is identical to natural IL2

  14. IL-12 and IL-18 Induction and Subsequent NKT Activation Effects of the Japanese Botanical Medicine Juzentaihoto

    Directory of Open Access Journals (Sweden)

    Ken Taniguchi

    2008-07-01

    Full Text Available In this study, we first measured some cytokine concentrations in the serum of patients treated with Juzentaihoto (JTT. Of the cytokines measured interleukin (IL -18 was the most prominently up-regulated cytokine in the serum of patients under long term JTT administration. We next evaluated the effects of JTT in mice, focusing especially on natural killer T (NKT cell induction. Mice fed JTT were compared to control group ones. After sacrifice, the liver was fixed, embedded and stained. Transmission electron microscope (TEM observations were performed. Although the mice receiving the herbal medicine had same appearance, their livers were infiltrated with massive mononuclear cells, some of which were aggregated to form clusters. Immunohistochemical staining revealed that there was abundant cytokine expression of IL-12 and IL-18 in the liver of JTT treated mice. To clarify what the key molecules that induce immunological restoration with JTT might be, we next examined in vitro lymphocyte cultures. Mononuclear cells isolated and prepared from healthy volunteers were cultured with and without JTT. Within 24 hours, JTT induced the IL-12 and IL-18 production and later (72 hours induction of interferon (IFN-gamma. Oral administration of JTT may induce the expression of IL-12 in the early stage, and IL-18 in the chronic stage, followed by NKT induction. Their activation, following immunological restoration could contribute to anti-tumor effects.

  15. Study on the changes of serum IL-2, IL-6 and TNF-α levels in patients with chronic glomerulonephritis

    International Nuclear Information System (INIS)

    Xie Jianping; Feng Jiangchao; Zhang Guoyuan; Xiong Gang; Tu Lirong; Xia Chengyun

    2003-01-01

    Objective: To investigate the changes of serum IL-2, IL-6 and TNF-α levels in patients with chronic glomerulonephritis of various types and stages. Methods: Serum IL-2, IL-6 and TNF-α levels were measured with RIA in 71 patients with chronic glomerulonephritis and 36 controls. Results: 1) Serum levels of IL-6 and TNF-α were significantly higher in patients with chronic glomerulonephritis than those in controls (p<0.01) but serum IL-2 levels were significantly lower in the patients (p<0.01). 2)Serum IL-6 and TNF-α levels were positively correlated to BUN levels (p<0.01). 3)There were no significant differences of these cytokines levels among the different types of patients (i.e. general type n=18, nephrotic type n=33 and hypertensive type n=20). Conclusion: These cytokines participated in the pathogenesis of chronic glomerulonephritis. Monitoring the changes of their serum levels was helpful for the management of the disease

  16. Exploring the Role of IL-32 in HIV-Related Kaposi Sarcoma.

    Science.gov (United States)

    Semango, George; Heinhuis, Bas; Plantinga, Theo S; Blokx, Willeke A M; Kibiki, Gibson; Sonda, Tolbert; Mavura, Daudi; Masenga, Elisante J; Nyindo, Mramba; van der Ven, Andre J A M; Joosten, Leo A B

    2018-01-01

    The intracellular proinflammatory mediator IL-32 is associated with tumor progression; however, the mechanisms remain unknown. We studied IL-32 mRNA expression as well as expression of other proinflammatory cytokines and mediators, including IL-1α, IL-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, the proangiogenic and antiapoptotic enzyme cyclooxygenase-2, the IL-8 receptor C-X-C chemokine receptor (CXCR) 1, and the intracellular kinase focal adhesion kinase-1. The interaction of IL-32 expression with expression of IL-6, TNF-α, IL-8, and cyclooxygenase-2 was also investigated. Biopsy specimens of 11 HIV-related, 7 non-HIV-related Kaposi sarcoma (KS), and 7 normal skin tissues (NSTs) of Dutch origin were analyzed. RNA was isolated from the paraffin material, and gene expression levels of IL-32 α, β, and γ isoforms, IL1a, IL1b, IL6, IL8, TNFA, PTGS2, CXCR1, and PTK2 were determined using real-time quantitative PCR. Significantly higher expression of IL-32β and IL-32γ isoforms was observed in HIV-related KS biopsy specimens compared with non-HIV-related KS and NST. The splicing ratio of the IL-32 isoforms showed IL-32γ as the highest expressed isoform, followed by IL-32β, in HIV-related KS cases compared with non-HIV-related KS and NST. Our data suggest a possible survival mechanism by the splicing of IL-32γ to IL-32β and also IL-6, IL-8, and CXCR1 signaling pathways to reverse the proapoptotic effect of the IL-32γ isoform, leading to tumor cell survival and thus favoring tumor progression. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  18. Effect of interferon-γ on NF-κB and cytokine IL-18 and IL-27 in acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Hongbo Meng

    2013-05-01

    Full Text Available The objective of our work was to evaluate the effect of interferon-γ (IFN-γ on cytokine expression in rat acute pancreatitis (AP.AP was introduced to rats which were divided into Control, AP and IFN-γ group. Rats in the AP and IFN-γ group were sacrificed as 6, 12 and 24 h after IFN-γ treatment. The serum amylase (AMA, endotoxin and cytokines were detected. The pathological examination and immunofluorescence staining of pancreas for TNF-α, NF-κB and IL-18 were performed.The serum AMA increased significantly at 6 h and reduced at 48 h after AP. The increase in IFN-γ was higher than that in AMA. IL-18 increased in the AP and IFN group, and IFN increased markedly at 48 h after AP. IL-27 reduced at 24 h after AP compared with AP group. In the AP group, the immunostaining of cytokines increased. In the IFN group, the edema in the pancreas was more severe, and NF-κB and IL-18 expression was higher than that in the other two groups. IFN-γ can increase serum IL-18 and reduce IL-27 in AP.IFN-γ can increase serum IL-18 and reduce serum IL-27 in AP. The increase in NF-κB and IL-18 may exert influence on pro-inflammatory cytokines to deteriorate inflammation in the pancreas. Thus, to control the IFN-γ might has promise to attenuate pancreatitis.

  19. Role of LncRNA-AF085935, IL-10 and IL-17 in Rheumatoid Arthritis Patients With Chronic Hepatitis C.

    Science.gov (United States)

    Sabry, Dina; Elamir, Azza; Mahmoud, Rania Hosny; Abdelaziz, Ahmed Ali; Fathy, Wael

    2017-05-01

    The current study aimed at testing the effect of corticosteroid therapy on serum levels of interleukin-10 (IL-10) and IL-17 as well as lncRNA-AF085935 in patients of rheumatoid arthritis (RA) associated with hepatitis C virus (HCV) and evaluating the usefulness of using these parameters to predict the therapeutic efficacy of steroids in these patients. Thirty healthy control subjects and 65 chronic HCV patients with RA were included in our study. Patients were subjected to clinical examination, abdominal ultrasound, and liver biopsy and received 6-methyl-prednisolone (PDN) 16 mg/day for 48 weeks. Blood samples were collected from all subjects and serum was separated to assess IL-10 and IL-17 by ELISA and HCV RNA and lncRNA-AF085935 by qRT-PCR. Our study revealed that there were significant increases in serum levels of IL-10, IL-17 and lncRNA-AF085935 in RA patients associated with HCV compared with healthy control subjects. Also there were significant increases in serum levels of IL-10 and HCV RNA and a significant decrease in serum level of IL-17 in patients after corticosteroid therapy, while lncRNA-AF085935 is not significantly changed. LncRNA-AF085935 might be a useful candidate biomarker for the early detection of RA associated with HCV, providing potential new strategies for early screening and therapy of these patients. IL-17 is a non-invasive prognostic marker to predict the efficacy of corticosteroid therapy in RA patients associated with chronic hepatitis C.

  20. Sequential IL-23 and IL-17 and increased Mmp8 and Mmp14 expression characterize the progression of an experimental model of periodontal disease in type 1 diabetes.

    Science.gov (United States)

    Silva, Juliete A F; Ferrucci, Danilo L; Peroni, Luis A; Abrahão, Patrícia G S; Salamene, Aline F; Rossa-Junior, Carlos; Carvalho, Hernandes F; Stach-Machado, Dagmar R

    2012-06-01

    Molecular mechanisms responsible for periodontal disease (PD) and its worsening in type 1 Diabetes Mellitus (DM1) remain unknown. Cytokine profile and expression levels of collagenases, Mmp14, and tissue inhibitors were determined, as were the numbers of neutrophils and macrophages in combined streptozotocin-induced DM1 and ligature-induced PD models. Increased IL-23 (80-fold) and Mmp8 expression (25-fold) was found in DM1. Ligature resulted in an IL-1β/IL-6 profile, increased expression of Mmp8, Mmp13, and Mmp14 (but not Mmp1), and transient expression of Timp1 and Reck in non-diabetics. PD in DM1 involved IL-1β (but not IL-6) and IL-23/IL-17, reduced IL-6 and IL-10, sustained Mmp8 and Mmp14, increased Mmp13 and reduced Reck expression in association with 20-fold higher counts of neutrophils and macrophages. IL-23 and Mmp8 expression are hallmarks of DM1. In association with the IL-1/IL-6 (Th1) response in PD, one found a secondary IL-17 (Th17) pathway in non-diabetic rats. Low IL-6/TNF-α suggest that the Th1 response was compromised in DM1, while IL-17 indicates a prevalence of the Th17 pathway, resulting in high neutrophil recruitment. Mmp8, Mmp13, and Mmp14 expression seems important in the tissue destruction during PD in DM1. PD-associated IL-1/IL-6 (Th1), IL-10, and Reck expression are associated with the acute-to-chronic inflammation transition, which is lost in DM1. In conclusion, IL-23/IL-17 are associated with the PD progression in DM1. Copyright © 2011 Wiley Periodicals, Inc.

  1. Identification of contact and respiratory sensitizers according to IL-4 receptor α expression and IL-2 production

    Energy Technology Data Exchange (ETDEWEB)

    Goutet, Michèle, E-mail: michele.goutet@inrs.fr; Pépin, Elsa; Langonné, Isabelle; Huguet, Nelly; Ban, Masarin

    2012-04-15

    Identification of allergenic chemicals is an important occupational safety issue. While several methods exist to identify contact sensitizers, there is currently no validated model to predict the potential of chemicals to act as respiratory sensitizers. Previously, we reported that cytometry analysis of the local immune responses induced in mice dermally exposed to the respiratory sensitizer trimellitic anhydride (TMA 10%) and contact sensitizer dinitrochlorobenzene (DNCB 1%) could identify divergent expression of several immune parameters. The present study confirms, first, that IgE-positive B cells, MHC class II molecules, interleukin (IL)-2, IL-4 and IL-4Rα can differentiate the allergic reactions caused by high doses of strong respiratory (TMA, phthalic anhydride and toluene diisocyanate) and contact sensitizers (DNCB, dinitrofluorobenzene and oxazolone). The second part of the study was designed to test the robustness of these markers when classing the weakly immunogenic chemicals most often encountered. Six respiratory allergens, including TMA (2.5%), five contact allergens, including DNCB (0.25%), and two irritants were compared at doses of equivalent immunogenicity. The results indicated that IL-4Rα and IL-2 can be reliably used to discriminate sensitizers. Respiratory sensitizers induced markedly higher IL-4Rα levels than contact allergens, while irritants had no effect on this parameter. Inversely, contact allergens tended to induce higher percentages of IL-2{sup +}CD8{sup +} cells than respiratory allergens. In contrast, the markers MHC-II, IgE and IL-4 were not able to classify chemicals with low immunogenic potential. In conclusion, IL-4Rα and IL-2 have the potential to be used in classifying a variety of chemical allergens. -- Highlights: ► Identification of chemical allergens is an important occupational safety issue. ► There is currently no model to predict the potential of chemicals to induce asthma. ► We analyze immune responses induced

  2. Identification of contact and respiratory sensitizers according to IL-4 receptor α expression and IL-2 production

    International Nuclear Information System (INIS)

    Goutet, Michèle; Pépin, Elsa; Langonné, Isabelle; Huguet, Nelly; Ban, Masarin

    2012-01-01

    Identification of allergenic chemicals is an important occupational safety issue. While several methods exist to identify contact sensitizers, there is currently no validated model to predict the potential of chemicals to act as respiratory sensitizers. Previously, we reported that cytometry analysis of the local immune responses induced in mice dermally exposed to the respiratory sensitizer trimellitic anhydride (TMA 10%) and contact sensitizer dinitrochlorobenzene (DNCB 1%) could identify divergent expression of several immune parameters. The present study confirms, first, that IgE-positive B cells, MHC class II molecules, interleukin (IL)-2, IL-4 and IL-4Rα can differentiate the allergic reactions caused by high doses of strong respiratory (TMA, phthalic anhydride and toluene diisocyanate) and contact sensitizers (DNCB, dinitrofluorobenzene and oxazolone). The second part of the study was designed to test the robustness of these markers when classing the weakly immunogenic chemicals most often encountered. Six respiratory allergens, including TMA (2.5%), five contact allergens, including DNCB (0.25%), and two irritants were compared at doses of equivalent immunogenicity. The results indicated that IL-4Rα and IL-2 can be reliably used to discriminate sensitizers. Respiratory sensitizers induced markedly higher IL-4Rα levels than contact allergens, while irritants had no effect on this parameter. Inversely, contact allergens tended to induce higher percentages of IL-2 + CD8 + cells than respiratory allergens. In contrast, the markers MHC-II, IgE and IL-4 were not able to classify chemicals with low immunogenic potential. In conclusion, IL-4Rα and IL-2 have the potential to be used in classifying a variety of chemical allergens. -- Highlights: ► Identification of chemical allergens is an important occupational safety issue. ► There is currently no model to predict the potential of chemicals to induce asthma. ► We analyze immune responses induced in mice

  3. Expression of TNF, IL-17A, IL-4 and IL-10 cytokines in irradiated peripheral blood mononuclear cells 'In vitro'

    International Nuclear Information System (INIS)

    Amaral, Ademir de Jesus; Leite, Lidía Lúcia Bezerra; Nascimento, Ayala Gomes do; Diniz, Ewerton Clementino; Silva, Gicielne Freitas da; Fernandes, Thiago de Salazar e; Silva, Edvane Borges da; Cavalcanti, Mariana Brayner; Veras, Robson Cavalcante; Medeiros, Isac Almeida de

    2017-01-01

    The aim of the present study was to determine and to compare the profile of cytokines produced by non-irradiated and irradiated peripheral blood mononuclear cells (PBMCs) and the possible application of this analysis as a biomarker of individual radiosensitivity. For this, peripheral blood (PB) samples were collected from seven healthy volunteers, and each sample divided in two aliquots: one aliquot was irradiated with a dose of 2 Gy (from a 6MV Linear Accelerator) and while the other one was kept non irradiated. All PBMCs were cultured in RPMI 1640 supplemented with 10% Bovine Fetal Serum for 48 hours at 37°C and 5% CO2. The cytokines TNF, IL-17A, IL-4 and IL-10 were measured by flow cytometry. Wilcoxon test was performed with the level of significance of 95%. In the irradiated samples it was observed a slight increase of the median of the level of cytokines TNF, IL-4 and IL-10 (from 1040.9 to 1196.1 pg/mL, from 127.3 to 138 pg/mL, and from 99.9 to 120.8 pg/mL, respectively) and a slight decrease in median of cytokines IL- 17A (from 841.1 to 799.4 pg/mL). In addition to this evidence, there was a high inter-individual variability of cytokine concentrations in response to irradiation. It was observed that some individuals are more responsive to the expression of some inflammatory proteins after exposure to X-rays. Although further studies are necessary, the hypothesis that raises is that these biomarkers could be predictor of future individual responses to ionizing radiation exposure. (author)

  4. induced pulmonary fibrosis in mice via regulation of IL

    African Journals Online (AJOL)

    Keywords: Saikosapoin D, Idiopathic pulmonary fibrosis, Myeloid differentiation factor, Hydroxyproline,. Interleukin, Interferon, IL-33/ST2 pathway ... corticosteroids and immunosuppressants is considered as common strategy for IPF ... medicine in China with broad spectrum bioactivities. Previous reports indicated that SSD.

  5. 75 FR 9015 - Environmental Impact Statement: Cook County, IL

    Science.gov (United States)

    2010-02-26

    ... DEPARTMENT OF TRANSPORTATION Federal Highway Administration Environmental Impact Statement: Cook County, IL AGENCY: Federal Highway Administration (FHWA), DOT. ACTION: Notice of Intent. SUMMARY: The FHWA is issuing this notice to advise the public that an environmental impact statement will be...

  6. Antibody-IL2 Fusion Protein Delivery by Gene Transfer

    National Research Council Canada - National Science Library

    Gan, Jacek

    1998-01-01

    .... The KS-IL2 fusion protein recognizes the KSA antigen expressed on a broad range of human carcinomas, including breast cancer and is effective at preventing outgrowth of the KSA positive, syngeneic...

  7. Oriente within, Nord without: il meridionismo e i romantici inglesi

    Directory of Open Access Journals (Sweden)

    Luigi Cazzato

    2012-11-01

    Full Text Available Per Voltaire (1773 prima ed Hegel (2010 poi, la storia del progresso del mondo ha viaggiato seguendo il percorso geo-politico e climatico aristotelico 1: dal dispotico Oriente verso il libero Occidente; mentre per Montesquieu (1994 essa ha viaggiato anche dai paesi caldi del Sud, timorosi come i vecchi, verso i paesi freddi del Nord, coraggiosi come i giovani. L’Europa non si è vista solo come l’altro rispetto all’Oriente, ma anche come l’altro rispetto al suo Meridione: il presente moderno del Nord di contro al passato antico del Sud. Nella seconda metà del Settecento, il secolo della nascita dell’orientalismo come sapere organico all’impresa coloniale dell’Occidente, vennero gettati anche i semi della pianta del meridionismo, sapere organico all’impresa della costruzione della moderna identità europea. I romantici inglesi coltivarono questa pianta.

  8. IL-10: A Multifunctional Cytokine in Viral Infections

    Directory of Open Access Journals (Sweden)

    José M. Rojas

    2017-01-01

    Full Text Available The anti-inflammatory master regulator IL-10 is critical to protect the host from tissue damage during acute phases of immune responses. This regulatory mechanism, central to T cell homeostasis, can be hijacked by viruses to evade immunity. IL-10 can be produced by virtually all immune cells, and it can also modulate the function of these cells. Understanding the effects of this multifunctional cytokine is therefore a complex task. In the present review we discuss the factors driving IL-10 production and the cellular sources of the cytokine during antiviral immune responses. We particularly focus on the IL-10 regulatory mechanisms that impact antiviral immune responses and how viruses can use this central regulatory pathway to evade immunity and establish chronic/latent infections.

  9. Targeting IL-17 with ixekizumab in patients with psoriasis

    DEFF Research Database (Denmark)

    Dyring Andersen, Beatrice; Skov, Lone; Zachariae, Claus

    2015-01-01

    Psoriasis is a multifactorial chronic inflammatory skin disease of unknown etiology. Knowledge of the pathophysiology of psoriasis has evolved and identified IL-17 as a key pro-inflammatory mediator in psoriasis creating new medical avenues. Several agents targeting IL-17 or its receptor are in c......Psoriasis is a multifactorial chronic inflammatory skin disease of unknown etiology. Knowledge of the pathophysiology of psoriasis has evolved and identified IL-17 as a key pro-inflammatory mediator in psoriasis creating new medical avenues. Several agents targeting IL-17 or its receptor...... are in clinical trials for the treatment of moderate-to-severe psoriasis. This review focuses on the biological rationale and the results of clinical trials with ixekizumab, a humanized IgG4 monoclonal antibody. The currently available Phase I to III data indicate that ixekizumab is a well-tolerated promising...

  10. Particelle e interazioni fondamentali Il mondo delle particelle

    CERN Document Server

    Braibant, Sylvie; Spurio, Maurizio

    2009-01-01

    Il libro intende fornire le conoscenze teoriche e fenomenologiche di base della struttura della materia a livello subatomico, presentando in maniera coordinata concetti e caratteristiche della fisica nucleare e della fisica delle particelle elementari. Partendo da un livello di base (nomenclatura, classificazione, tecniche di accelerazione e di rivelazione delle particelle elementari), si passano in rassegna le proprietà delle interazioni fondamentali (elettromagnetica, debole e forte). Vengono descritti poi i risultati che confermano il Modello Standard del microcosmo, per terminare con i problemi ancora aperti. Per esempio, la violazione di CP attualmente misurata non spiega l’asimmetria materia-antimateria dell’Universo osservata; le oscillazioni dei neutrini e la quantità di materia oscura prevista dalla cosmologia sembrano richiedere qualcosa oltre il Modello Standard. Il libro è organizzato in modo da coprire gli argomenti dei corsi di Fisica Nucleare e Subnucleare della Laurea in Fisica, e dei c...

  11. Inflammasome-independent regulation of IL-1-family cytokines

    NARCIS (Netherlands)

    Netea, M.G.; Veerdonk, F.L. van de; Meer, J.W.M. van der; Dinarello, C.A.; Joosten, L.A.B.

    2015-01-01

    Induction, production, and release of proinflammatory cytokines are essential steps to establish an effective host defense. Cytokines of the interleukin-1 (IL-1) family induce inflammation and regulate T lymphocyte responses while also displaying homeostatic and metabolic activities. With the

  12. IL-33 Drives Augmented Responses to Ozone in Obese Mice.

    Science.gov (United States)

    Mathews, Joel A; Krishnamoorthy, Nandini; Kasahara, David Itiro; Cho, Youngji; Wurmbrand, Allison Patricia; Ribeiro, Luiza; Smith, Dirk; Umetsu, Dale; Levy, Bruce D; Shore, Stephanie Ann

    2017-02-01

    Ozone increases IL-33 in the lungs, and obesity augments the pulmonary effects of acute ozone exposure. We assessed the role of IL-33 in the augmented effects of ozone observed in obese mice. Lean wildtype and obese db/db mice were pretreated with antibodies blocking the IL-33 receptor, ST2, and then exposed to ozone (2 ppm for 3 hr). Airway responsiveness was assessed, bronchoalveolar lavage (BAL) was performed, and lung cells harvested for flow cytometry 24 hr later. Effects of ozone were also assessed in obese and lean mice deficient in γδ T cells and their wildtype controls. Ozone caused greater increases in BAL IL-33, neutrophils, and airway responsiveness in obese than lean mice. Anti-ST2 reduced ozone-induced airway hyperresponsiveness and inflammation in obese mice but had no effect in lean mice. Obesity also augmented ozone-induced increases in BAL CXCL1 and IL-6, and in BAL type 2 cytokines, whereas anti-ST2 treatment reduced these cytokines. In obese mice, ozone increased lung IL-13+ innate lymphoid cells type 2 (ILC2) and IL-13+ γδ T cells. Ozone increased ST2+ γδ T cells, indicating that these cells can be targets of IL-33, and γδ T cell deficiency reduced obesity-related increases in the response to ozone, including increases in type 2 cytokines. Our data indicate that IL-33 contributes to augmented responses to ozone in obese mice. Obesity and ozone also interacted to promote type 2 cytokine production in γδ T cells and ILC2 in the lungs, which may contribute to the observed effects of IL-33. Citation: Mathews JA, Krishnamoorthy N, Kasahara DI, Cho Y, Wurmbrand AP, Ribeiro L, Smith D, Umetsu D, Levy BD, Shore SA. 2017. IL-33 drives augmented responses to ozone in obese mice. Environ Health Perspect 125:246-253; http://dx.doi.org/10.1289/EHP272.

  13. Il valore del piuccheperfetto nella lingua della stampa Italian contempiranea

    Directory of Open Access Journals (Sweden)

    Mitja Skubic

    1966-12-01

    Full Text Available Partiamo dal presupposto valido per un campo seniantico: se introduciamo nel campo semantico un elemento nuovo, il campo si tiorganizza, vale a dire, un cambiamento semantico di un elemento influisce, sulla semantica di altri elementi, o almeno di quelli  piú vicini. Se è così, anche la sparizione di un elemento provoca una nuova spartizione o una nuova delimitazione dei concetti di tutto il campo semantico almena degli elementi più vicini.

  14. Transplant tolerance: a new role for IL-34

    OpenAIRE

    Kim, James I.; Turka, Laurence A.

    2015-01-01

    Immune-suppressive cell populations, including Tregs and suppressor monocytes, have been implicated in long-term survival of allografts in both human transplant recipients and animal models. The factors that drive differentiation and function of these cell populations are not completely understood. In this issue, Bézie and colleagues identify IL-34 as an important mediator of allograft tolerance in a rat model of heart transplantation. Their data support a model in which IL-34 production by T...

  15. Production and characterization of genetically modified human IL-11 variants.

    Science.gov (United States)

    Sano, Emiko; Takei, Toshiaki; Ueda, Takuya; Tsumoto, Kouhei

    2017-02-01

    Interleukin-11 (IL-11) has been expected as a drug on severe thrombocytopenia caused by myelo-suppressive chemotherapy. Whereas, development of IL-11 inhibitor is also expected for a treatment against IL-11 related cancer progression. Here, we will demonstrate the creation of various kinds of genetically modified hIL-11s. Modified vectors were constructed by introducing N- or O-glycosylation site on the region of hIL-11 that does not belong to the core α-helical motif based on the predicted secondary structure. N-terminal (N: between 22 to 23 aa), the first loop (M1:70 to 71 aa), the second loop (M2:114-115 aa), the third loop (M3:160-161 aa) and C-terminal (C: 200- aa) were selected for modification. A large scale production system was established and the characteristics of modified hIL-11s were evaluated. The structure was analyzed by amino acid sequence and composition analysis and CD-spectra. Glycan was assessed by monosaccharide composition analysis. Growth promoting activity and biological stability were analyzed by proliferation of T1165 cells. N-terminal modified proteins were well glycosylated and produced. Growth activity of 3NN with NASNASNAS sequence on N-terminal was about tenfold higher than wild type (WT). Structural and biological stabilities of 3NN were also better than WT and residence time in mouse blood was longer than WT. M1 variants lacked growth activity though they are well glycosylated and secondary structure is very stable. Both of 3NN and OM1 with AAATPAPG on M1 associated with hIL-11R strongly. These results indicate N-terminal and M1 variants will be expected for practical use as potent agonists or antagonists of hIL-11. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Association between IL-1β polymorphisms and gastritis risk

    Science.gov (United States)

    Sun, Xiaoming; Cai, Hongxing; Li, Zhouru; Li, Shanshan; Yin, Wenjiang; Dong, Guokai; Kuai, Jinxia; He, Yihui; Jia, Jing

    2017-01-01

    Abstract Background: Helicobacter pylori (H. pylori) infection of the human stomach regularly leads to chronic gastric inflammation. The cytokine gene interleukin (IL)-1β has been implicated in influencing the pathology of inflammation induced by H. pylori infection. Currently, several studies have been carried out to investigate the association of IL-1β-511 (rs16944) and IL-1β-31 (rs1143627) polymorphisms with gastritis risk; however, the results are inconsistent and inconclusive. To assess the effect of IL-1β polymorphisms on gastritis susceptibility, we conducted a meta-analysis. Methods: Up to March 15, 2016, 2205 cases and 2289 controls were collected from 12 published case–control studies. Summarized odds ratios and corresponding 95% confidence intervals (CIs) for IL-1β-511 and IL-1β-31 polymorphisms and gastritis risk were estimated using fixed- or random-effects models when appropriate. Heterogeneity was assessed by chi-squared-based Q-statistic test, and the sources of heterogeneity were explored by subgroup analyses and logistic meta-regression analyses. Publication bias was evaluated by Begg funnel plot and Egger test. Sensitivity analyses were also performed. Results: The results provided evidences that the single nucleotide polymorphisms (SNPs) in IL-1β-31 might be associated with the gastritis risk, especially in the Caucasian population, while SNPs in the IL-1β-511 might not be. Conclusion: Our studies may be helpful in supplementing the disease monitoring of gastritis in the future, and additional studies to determine the exact molecular mechanisms might inspire interventions to protect the susceptible subgroups. PMID:28151895

  17. Le forze della natura il nuovo orizzonte della fisica

    CERN Document Server

    Davies, Paul C W

    1990-01-01

    Vero "cavallo di razza" della divulgazione scientifica, Paul Davies è uno dei rari fisici che sanno farsi seguire dal lettore comune anche quando affrontano argomenti difficili. Ne è una prova il presente volume, una delle migliori illustrazioni disponibili del microcosmo atomico e dell'incredibile fauna che lo abita : non solo la familiare triade protone-elettrone-neutrone, ma le ben più intriganti realtà che vanno sotto il nome di "colore", "incanto", stranezza".

  18. IL-9-Producing Mast Cell Precursors and Food Allergy

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0517 TITLE: IL-9-Producing Mast Cell Precursors and Food Allergy PRINCIPAL INVESTIGATOR: Dr. Simon P. Hogan PhD...IL-9-Producing Mast Cell Precursors and Food Allergy 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Yui Hsi Wang, Sunil...for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT: Food allergy is a harmful immune reaction driven by uncontrolled type-2

  19. Immunosensore amperometrico competitivo per la determinazione di p53 in urina: metodo di screening rapido e non invasivo per la diagnosi precoce del carcinoma della vescica

    OpenAIRE

    Bianchi, Maria Vittoria

    2017-01-01

    La proteina p53, è il soppressore tumorale più studiato e conosciuto ed è un fondamentale fattore trascrizionale, la cui azione viene modulata in risposta a diversi stimoli genetici e ambientali. Essa rappresenta un’importante difesa contro lo sviluppo del cancro e la sua progressione, agendo come un “guardiano del genoma”. Studi clinici hanno evidenziato che lo sviluppo del Carcinoma a cellule transizionali della vescica (BTCC) può determinare una significativa sovra espressione di p53 ne...

  20. IL-17 inhibits chondrogenic differentiation of human mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Masahiro Kondo

    Full Text Available OBJECTIVE: Mesenchymal stem cells (MSCs can differentiate into cells of mesenchymal lineages, such as osteoblasts and chondrocytes. Here we investigated the effects of IL-17, a key cytokine in chronic inflammation, on chondrogenic differentiation of human MSCs. METHODS: Human bone marrow MSCs were pellet cultured in chondrogenic induction medium containing TGF-β3. Chondrogenic differentiation was detected by cartilage matrix accumulation and chondrogenic marker gene expression. RESULTS: Over-expression of cartilage matrix and chondrogenic marker genes was noted in chondrogenic cultures, but was inhibited by IL-17 in a dose-dependent manner. Expression and phosphorylation of SOX9, the master transcription factor for chondrogenesis, were induced within 2 days and phosphorylated SOX9 was stably maintained until day 21. IL-17 did not alter total SOX9 expression, but significantly suppressed SOX9 phosphorylation in a dose-dependent manner. At day 7, IL-17 also suppressed the activity of cAMP-dependent protein kinase A (PKA, which is known to phosphorylate SOX9. H89, a selective PKA inhibitor, also suppressed SOX9 phosphorylation, expression of chondrogenic markers and cartilage matrix, and also decreased chondrogenesis. CONCLUSIONS: IL-17 inhibited chondrogenesis of human MSCs through the suppression of PKA activity and SOX9 phosphorylation. These results suggest that chondrogenic differentiation of MSCs can be inhibited by a mechanism triggered by IL-17 under chronic inflammation.

  1. Il2rg gene-targeted severe combined immunodeficiency pigs.

    Science.gov (United States)

    Suzuki, Shunichi; Iwamoto, Masaki; Saito, Yoriko; Fuchimoto, Daiichiro; Sembon, Shoichiro; Suzuki, Misae; Mikawa, Satoshi; Hashimoto, Michiko; Aoki, Yuki; Najima, Yuho; Takagi, Shinsuke; Suzuki, Nahoko; Suzuki, Emi; Kubo, Masanori; Mimuro, Jun; Kashiwakura, Yuji; Madoiwa, Seiji; Sakata, Yoichi; Perry, Anthony C F; Ishikawa, Fumihiko; Onishi, Akira

    2012-06-14

    A porcine model of severe combined immunodeficiency (SCID) promises to facilitate human cancer studies, the humanization of tissue for xenotransplantation, and the evaluation of stem cells for clinical therapy, but SCID pigs have not been described. We report here the generation and preliminary evaluation of a porcine SCID model. Fibroblasts containing a targeted disruption of the X-linked interleukin-2 receptor gamma chain gene, Il2rg, were used as donors to generate cloned pigs by serial nuclear transfer. Germline transmission of the Il2rg deletion produced healthy Il2rg(+/-) females, while Il2rg(-/Y) males were athymic and exhibited markedly impaired immunoglobulin and T and NK cell production, robustly recapitulating human SCID. Following allogeneic bone marrow transplantation, donor cells stably integrated in Il2rg(-/Y) heterozygotes and reconstituted the Il2rg(-/Y) lymphoid lineage. The SCID pigs described here represent a step toward the comprehensive evaluation of preclinical cellular regenerative strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. IL-22 Protects against Tissue Damage during Cutaneous Leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Ciara Gimblet

    Full Text Available Cutaneous leishmaniasis is a disease characterized by ulcerating skin lesions, the resolution of which requires an effective, but regulated, immune response that limits parasite growth without causing permanent tissue damage. While mechanisms that control the parasites have been well studied, the factors regulating immunopathologic responses are less well understood. IL-22, a member of the IL-10 family of cytokines, can contribute to wound healing, but in other instances promotes pathology. Here we investigated the role of IL-22 during leishmania infection, and found that IL-22 limits leishmania-induced pathology when a certain threshold of damage is induced by a high dose of parasites. Il22-/- mice developed more severe disease than wild-type mice, with significantly more pathology at the site of infection, and in some cases permanent loss of tissue. The increased inflammation was not due to an increased parasite burden, but rather was associated with the loss of a wound healing phenotype in keratinocytes. Taken together, these studies demonstrate that during cutaneous leishmaniasis, IL-22 can play a previously unappreciated role in controlling leishmania-induced immunopathology.

  3. Experimental neurocysticercosis: absence of IL-4 induces lower encephalitis

    Directory of Open Access Journals (Sweden)

    Hidelberto Matos Silva

    Full Text Available ABSTRACT Neurocysticercosis (NCC is the most severe clinical manifestation of cysticercosis. One of the factors responsible for its symptomatology is the host inflammatory response. Therefore the influence of interleukin 4 (IL-4 on the induction of encephalitis in experimental NCC was evaluated. Methods BALB/c (WT and BALB/c (IL-4-KO mice were inoculated intracranially with Taenia crassiceps cysticerci and euthanized at 7, 30, 60 and 90 days later, the encephala removed and histopathologically analyzed. Results The absence of IL-4 induced greater parasitism. In the initial phase of the infection, IL-4-KO showed a lower intensity in the inflammatory infiltration of polimorphonuclear cells in the host-parasite interface and intra-parenquimatous edema. The IL-4-KO animals, in the late phase of the infection, showed lower intensity of ventriculomegaly, encephalitis, and meningitis, and greater survival of the parasites in comparison with the WT animals. Conclusion The absence of IL-4 induced lower inflammatory infiltration, ventriculomegaly and perivasculitis in experimental NCC.

  4. Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

    Science.gov (United States)

    Diegelmann, Julia; Beigel, Florian; Zitzmann, Kathrin; Kaul, Artur; Göke, Burkhard; Auernhammer, Christoph J; Bartenschlager, Ralf; Diepolder, Helmut M; Brand, Stephan

    2010-12-08

    Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV.

  5. A state of acquired IL-10 deficiency in 0.4% of Danish blood donors

    DEFF Research Database (Denmark)

    de Lemos Rieper, Carina; Galle, Pia; Pedersen, Bente Klarlund

    2010-01-01

    Autoantibodies against a variety of growth factors and cytokines are present in preparations of pooled normal human IgG, such as IVIg. The present study demonstrated that healthy Danish blood donors produced high concentrations of anti-IL-10 IgG antibodies that bound IL-10 with extremely high...... avidity. The antibodies were of IgG class, polyclonally derived and acted as competitive IL-10 inhibitors in vitro, substantially inhibiting cellular IL-10 receptor binding and neutralizing IL-10 activity in vitro. The antibodies failed to bind viral forms of IL-10 or other members of the human IL-10...... family (IL-19, IL-20, IL-22, IL-24, IL-26, IL-28A, IL-28B, IL-29). The production of anti-IL-10 antibodies was stable from months to years, and high positive donors were likely to acquire a state of IL-10 deficiency in the circulation during this period. Anti-IL-10 antibodies were readily measurable even...

  6. Development of IL-17-mediated Delayed-Type Hypersensitivity Is Not Affected by Down-Regulation of IL-25 Expression

    Directory of Open Access Journals (Sweden)

    Akina Ishii

    2010-01-01

    Conclusions: IL-25 is not essential for differentiation of Th1, Th2 and Th17 cells in the sensitization phase or induction of local inflammation in the elicitation phase of the mBSA-induced DTH reaction.

  7. Alpha-mangostin suppresses IL-6 and IL-8 expression in P. gingivalis LPS-stimulated human gingival fibroblasts.

    Science.gov (United States)

    Yiemwattana, Ichaya; Kaomongkolgit, Ruchadaporn

    2015-09-01

    This study aims to investigate the effect of alpha-mangostin on interleukin (IL)-6 and IL-8 expression in human gingival fibroblasts (HGFs). HGFs were challenged with Porphyromonas gingivalis LPS and then treated with various concentrations of alpha-mangostin. The cytotoxicity was determined using MTS assay and cytokine expressions were evaluated by Real-time PCR and ELISA. The results showed that 5 μg/ml P. gingivalis LPS and alpha-mangostin at 1 µg/ml or less did not affect the viability of HGFs. Alpha-mangostin reduced IL-6 and IL-8 mRNA and protein in P. gingivalis LPS-stimulated HGFs. These findings suggested that alpha-mangostin might be used as an adjunct to the periodontal therapy.

  8. Increased systemic and epidermal levels of IL-17A and IL-1β promotes progression of non-segmental vitiligo.

    Science.gov (United States)

    Bhardwaj, Supriya; Rani, Seema; Srivastava, Niharika; Kumar, Ravinder; Parsad, Davinder

    2017-03-01

    Non-segmental vitiligo (NSV) results from autoimmune destruction of melanocytes. The altered levels of various cytokines have been proposed in the pathogenesis of vitiligo. However, the exact immune mechanisms have not yet been fully elucidated. To investigate the role of epidermal and systemic cytokines in active and stable NSV patients. Serum levels of inflammatory cytokines were checked in 42 active and 30 stable NSV patients with 30 controls. The lesional, perilesional and normal skin sections were subjected to H&E staining. The mRNA expression of inflammatory cytokines and their respective receptors were assessed by quantitative PCR in lesional skin of both active and stable NSV skin. The MITF and IL-17A were immunolocalized in lesional, perilesional and normal skin tissue. Significant increase in the expression of inflammatory cytokines, IL-17A, IL-1β and TGF-β was observed in active patients, whereas no change was observed in stable patients. A marked reduction in epidermal thickness was observed in lesional skin sections. Significant increase in IL-17A and significant decrease in microphthalmia associated transcription factor (MITF) expression was observed in lesional and perilesional skin sections. Moreover, qPCR analysis showed significant alterations in the mRNA levels of IL-17A, IL-1β, IFN-γ, TGF-β and their respective receptors in active and stable vitiligo patient samples. Increased levels of IL-17A and IL-1β cytokines and decreased expression of MITF suggested a possible role of these cytokines in dysregulation of melanocytic activity in the lesional skin and hence might be responsible for the progression of active vitiligo. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. IL17A polymorphism and elevated IL17A serum levels are associated with oral lichen planus.

    Science.gov (United States)

    Gueiros, L A; Arão, T; Souza, T; Vieira, C L; Gomez, R S; Almeida, O P; Lodi, G; Leão, J C

    2018-04-01

    The aim of this study was to evaluate the association of IL17A G197A polymorphism and serum levels with oral lichen planus (OLP) susceptibility and clinical presentation. Eighty-three individuals diagnosed with OLP and 99 healthy controls (C) were consecutively recruited. All participants had desquamating oral mucosal cells collected and DNA isolated for IL17A (G197A) genotyping. Blood samples of 42 OLP individuals and 23 healthy controls were collected for evaluation of IL17A serum levels. IL17A G197A genotypes were associated with an increased chance of having OLP (GA/AA × GG, OR = 3.44, 95% CI = 1.87-6.33, p < .001). Overall A carriers (GA or AA) were more common in OLP (38.1%) than in C (20.2%; OR = 2.43, 95% CI = 1.53-3.87, p < .001). Serum levels of IL17A were higher among patients with OLP than in healthy controls (reticular, p = .0003; erosive, p < .001), but no difference was found among the disease types. IL17A G197A is associated with a higher susceptibility of developing OLP and these patients seem to present a considerable increase in IL17A serum levels. These findings suggest that Th17 cells, and IL17A in particular, may play a pivotal role in OLP pathogenesis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  10. IL-33 induces IL-9 production in human CD4+ T cells and basophils

    DEFF Research Database (Denmark)

    Blom, Lars; Poulsen, Britta Cathrina; Jensen, Bettina M.

    2011-01-01

    blood. TGF-β has been described as a critical factor for IL-9 induction in Th2 cells; however, we found that TGF-β also induces co-production of IL-9 in purified, naïve (>99%) CD4(+)CD45RA(+)CD45RO(-)CD25(-) T cells differentiated towards a Th1 profile. Subsequently, it was demonstrated that TGF...

  11. Effect of Proinflammatory Cytokines (IL-6, TNF-α, and IL-1β on Clinical Manifestations in Indian SLE Patients

    Directory of Open Access Journals (Sweden)

    Vinod Umare

    2014-01-01

    Full Text Available Systemic lupus erythematosus (SLE is an inflammatory rheumatic disease characterized by production of autoantibodies and organ damage. Elevated levels of cytokines have been reported in SLE patients. In this study we have investigated the effect of proinflammatory cytokines (IL-6, TNF-α, and IL-1β on clinical manifestations in 145 Indian SLE patients. One hundred and forty-five healthy controls of the same ethnicity served as a control group. Clinical disease activity was scored according to SLEDAI score. Accordingly, 110 patients had active disease and 35 patients had inactive disease. Mean levels of IL-6, TNF-α, and IL-1β were found to be significantly higher in SLE patients than healthy controls (P<0.001. Mean level of IL<