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

Responsabilità giuridica e scienze sperimentali sul vivente

Directory of Open Access Journals (Sweden)

Patrick Nerhot

2017-12-01

Full Text Available SOMMARIO: 1. Il "vivente": inoperosità dei concetti della filosofia profana dei Lumi - 2. La ricerca-costruzione di una infinita-fine - 3. Le scienze "sperimentali" come la non distinzione tra "causa" e "effetto" - 4. La nuova questione di metodo posta al "vivente" - 5. La sfida di una etica come adeguazione tra etica e metodo.

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.

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...

Un universo comprensibile interazione tra scienza e teologia

CERN Document Server

Coyne, George V

2009-01-01

Perché il nostro mondo è comprensibile? La domanda sembra così banale, che solo pochi trovano il coraggio di porsela. In questo libro esploreremo le radici profonde del mistero della razionalità. L’indagine sulla razionalità del mondo cominciò duemilacinquecento anni or sono, quando un manipolo di audaci pensatori avviarono l’impresa di cercare di capire la Natura con la sola forza della ragione, rifiutando le comode e futili spiegazioni fornite da miti e leggende. Attraverso molte avventure filosofiche e teologiche, alla fine il concetto greco di razionalità pose le basi di un modo nuovo e rivoluzionario di pensare: quello del metodo scientifico, destinato a trasformare il mondo. Quando consideriamo i frutti più recenti dell’indagine sulla razionalità del mondo – la teoria della relatività, la meccanica quantistica, l’unificazione delle leggi fisiche, la gravitazione quantistica – viene da chiedersi: quali sono i limiti del metodo scientifico? Il principio fondamentale del pensiero razi...

Accessibilità e fruibilità del patrimonio architettonico: occasioni per una sostenibilità “sociale” del recupero

Directory of Open Access Journals (Sweden)

Alessandro Greco

2012-12-01

Full Text Available Il tema dell’accessibilità e della fruibilità del patrimonio storico – architettonico sta assumendo sempre più rilevanza nel contesto nazionale, e in quello europeo più in generale, anche per le importanti funzioni che normalmente vengono inserite in contenitori edilizi dall’elevato valore culturale e documentale, collocati spesso nel centro storico delle città oppure in aree di elevato pregio ambientale.Il contributo propone riflessioni di carattere generale sull’importanza “sociale” dell’accessibilità al patrimonio edilizio storico e offre spunti per un approccio alla progettazione dell’accessibilità secondo un metodo consapevole della complessità del tema, partecipato e multidisciplinare. Il testo si completa con l’illustrazione di due ricerche applicate (una alla scala urbana e una alla scala edilizia sviluppate secondo tale metodo.

Il metodo storico nella critica testuale

OpenAIRE

Giangrande, Giusseppe

2008-01-01

Se ofrecen ejemplos de cómo es posible explicar por medio de un enfoque histórico pasajes controvertidos de autores griegos y latinos. Passages of Greek and Latin authors which many a critic cannot understand can often be explained by placing them in the proper historical perspective.

Survey of Pulsed Neutron Source Methods for Multiplying Media; Methodes des Neutrons Pulses Pour l'Etude des Milieux Multiplicateurs; Obzor metodov s ispol'zovaniem istochnikov impul'snykh nejtronov dlya razmnozhayushchej sredy; Estudio Panoramico de los Metodos de Empleo de Fuentes de Neutrons Pulsados en Medios Multiplicadores

Energy Technology Data Exchange (ETDEWEB)

Garelis, E. [General Electric Company, Vallecitos Atomic Laboratory, Pleasanton, CA (United States)

1965-10-15

-Small-L ). Il discute en outre l'emploi des methodes qui sont fondees sur la reponse a des impulsions pseudoaleatoires et utilisent une correlation entre l'entree et la sortie, pour la determination de la fonction de Green d'un milieu multiplicateur. H montre que les renseignements obtenus par ces methodes sont identiques a ceux fournis par les methodes de la source puisee a repetition, ce qui permet d'appliquer aux premieres les procedes qui ont ete mis au point pour les secondes. (author) [Spanish] En los ultimos afios ha habido dos tendencias principales acerca de la manera mas eficaz de medir la reactividad de parada, empleando fuentes de neutrones pulsados: la primera preconizaba el empleo de metodos tradicionales de medicion con fuentes neutronicas reiteradamente pulsadas, y la segunda propugnaba la aplicacion de metodos basados en una tecnica seudoaleatoria de respuesta a los impulsos, utilizando una correlacion entre los datos de entrada y los de salida. La informacion obtenida con una y otra tecnica es la misma; en teoria, ambos metodos sirven para determinar la funcion de respuesta. Se resefia el desarrollo de las tecnicas de empleo de fuentes de neutrones pulsados aplicadas a sistemas termicos con miras a medir la reactividad, desde los primeros intentos de Sjoestrand hasta el reciente metodo (k{beta}/ Script-Small-L ). Con el metodo usual de empleo de estas fuentes, la propiedad que se procuia determinar es la funcion de Green del conjunto subercritico empleado, es decir, la respuesta del reactor a una fuente de neutrones de funcion delta. El decrecimiento exponencial (e{sup {alpha}t}) de la funcion de Green proporciona una constante de decrecimiento de los neutrones instantaneos que es independiente del espacio. El autor examina los metodos para obtener el valor de la reactividad partiendo de la medida de a, como por ejemplo el metodo de la medicion de la criticidad por neutrones retardados a y el reciente metodo (k{beta}/ Script-Small-L ). Seguidamente examina el

Valutazione dell'appropriatezza dei ricoveri in un Policlinico Universitario: analisi mediante l'uso comparativo dei sistemi di classificazione isogravitá APR-DRG e Disease Staging e del PRUO

Directory of Open Access Journals (Sweden)

M. Volpe

2003-05-01

Full Text Available

Obiettivi: valutare l’appropriatezza organizzativa dei ricoveri effettuati in un Policlinico Universitario attraverso la comparazione di due metodi, dei quali uno basato sui dati della scheda di dimissione ospedaliera ed utilizza, rispettivamente, i sistemi di classificazione iso-gravità APR-DRG e Disease Staging e l’altro sulla revisione delle cartelle cliniche mediante il PRUO.

Metodi: oggetto di analisi sono i ricoveri ordinari effettuati nell’anno 2001 ed afferenti ai DRG inclusi nella delibera della Giunta Regionale del Lazio 864/2002 che recepisce il D.P.C.M. 29/11/2001 sui livelli essenziali di assistenza.

Risultati: i risultati evidenziano che le due varianti del
metodo basato sulla SDO (metodo APPRO mostrano quote di ricoveri inappropriati sovrapponibili rispetto al complesso dei ricoveri oggetto di analisi, ma con differenze anche rilevanti tra APR-DRG e Disease Staging in relazione ai singoli DRG considerati, riconducibili ai diversi algoritmi di attribuzione del livello di severità utilizzati dai due sistemi. L’analisi campionaria effettuata con il metodo PRUO su casi afferenti ai DRG della DGR 864/2002 caratterizzati da livelli di severità minimi evidenzia una proporzione di ricoveri inappropriati superiore a quella determinata tramite i metodi basati sulla SDO. Tale differenza è verosimilmente dovuta al ruolo del valore delle soglie percentuali di accettabilità individuate dalla Regione Lazio per ciascun DRG: le quote di ricoveri che eccedono tali soglie sono considerate inappropriate.

Conclusioni: sulla base dei risultati ottenuti gli autori
descrivono gli interventi organizzativi adottati per ottimizzare il contesto di erogazione delle prestazioni
oggetto di analisi, discutono vantaggi e limiti dei metodi SDO-based e del metodo analitico PRUObased e ne propongono l�

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

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

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.

Genealogy of the body and genealogical body

Directory of Open Access Journals (Sweden)

Paola Cecchetti

2011-06-01

Full Text Available A partire da un quadro di Frida Kahlo intitolato I miei nonni, i miei genitori e io le due autrici indagano quel testo-immagine che sta all'origine dello stile di lettura del soggetto. Posto dinanzi alla stessa immagine, ciascuno ne fa una rappresentazione estremamente personale, un quadro delle proprie vicissitudini interne e dei legami transgenerazionali che lo hanno segnato. I momenti nei quali si articola la ricerca sono tre: la scrittura dell’occhio, il ricalco e il percorso della mano, il negativo e l’assenza.A essi segue poi lo psicodramma. Tale successione temporale abitua a vedere nell'immagine disegnata l'immagine negata, assente. L'esperienza sembra aver creato un nuovo metodo di indagine della psiche rispetto al transgenerazionale, metodo che intreccia il genogramma (di origini sistemico-relazionale e lo psicodramma analitico, e che viene chiamato “genodramma psicoanalitico”. Partendo da un dato clinico – l'esilità del legame che le nuove generazioni intrattengono con quelle che le precedono, sembra vogliano rinegoziare il contratto narcisistico che assegna al passato il posto dell'assenza. Il contributo si chiude con un interrogativo: “Alla ricerca di che cosa? Della presenza o, meglio, delle tracce lasciate nel soggetto dall'Altro che precede l'insediamento dell'Io”.

IL-22R Ligands IL-20, IL-22, and IL-24 Promote Wound Healing in Diabetic db/db Mice.

Science.gov (United States)

Kolumam, Ganesh; Wu, Xiumin; Lee, Wyne P; Hackney, Jason A; Zavala-Solorio, Jose; Gandham, Vineela; Danilenko, Dimitry M; Arora, Puneet; Wang, Xiaoting; Ouyang, Wenjun

2017-01-01

Diabetic foot ulcers (DFU) are one of the major complications in type II diabetes patients and can result in amputation and morbidity. Although multiple approaches are used clinically to help wound closure, many patients still lack adequate treatment. Here we show that IL-20 subfamily cytokines are upregulated during normal wound healing. While there is a redundant role for each individual cytokine in this subfamily in wound healing, mice deficient in IL-22R, the common receptor chain for IL-20, IL-22, and IL-24, display a significant delay in wound healing. Furthermore, IL-20, IL-22 and IL-24 are all able to promote wound healing in type II diabetic db/db mice. Mechanistically, when compared to other growth factors such as VEGF and PDGF that accelerate wound healing in this model, IL-22 uniquely induced genes involved in reepithelialization, tissue remodeling and innate host defense mechanisms from wounded skin. Interestingly, IL-22 treatment showed superior efficacy compared to PDGF or VEGF in an infectious diabetic wound model. Taken together, our data suggest that IL-20 subfamily cytokines, particularly IL-20, IL-22, and IL-24, might provide therapeutic benefit for patients with DFU.

La riscoperta della stereoscopia per la rappresentazione dello spazio architettonico

Directory of Open Access Journals (Sweden)

Simone Garagnani

2011-06-01

Full Text Available Il progressivo sviluppo dei metodi della rappresentazione grafica nel corso della storia è stato possibile in virtù della scoperta di strumenti e tecniche appartenenti al loro tempo: questo continuo progresso delle modalità di “raccontare” l’architettura è tuttora in corso di evoluzione, costituendo il fondamento di ogni strategia informativa e di comunicazione del progetto. Il sempre più pervasivo trattamento digitale dell’informazione, sia essa grafica che testuale, ha condotto ad una progressiva riscoperta di approcci tradizionali nella descrizione dello spazio costruito, declinandoli alle nuove tecnologie informatiche per amplificarne possibilità e valenze. È il caso della stereoscopia, diffuso metodo ottocentesco adottato in fotografia per rendere spaziale la percezione dell’immagine sfruttando la visione binoculare; oggi i modelli tridimensionali e le immagini digitali catturate da apposite fotocamere rendono l’approccio stereoscopico di immediato utilizzo anche per i profani della rappresentazione, semplificando e rendendo trasparenti i concetti di geometria proiettiva alla base del metodo. Questo contributo intende indagare le funzionalità, i vantaggi e le criticità della tecnologia stereoscopica immersiva nella moderna comunicazione del progetto d’architettura.

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

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

Th-17 regulatory cytokines IL-21, IL-23, and IL-6 enhance neutrophil production of IL-17 cytokines during asthma.

Science.gov (United States)

Halwani, Rabih; Sultana, Asma; Vazquez-Tello, Alejandro; Jamhawi, Amer; Al-Masri, Abeer A; Al-Muhsen, Saleh

2017-11-01

In a subset of severe asthma patients, chronic airway inflammation is associated with infiltration of neutrophils, Th-17 cells and elevated expression of Th-17-derived cytokines (e.g., interleukin [IL]-17, IL-21, IL-22). Peripheral neutrophils from allergic asthmatics are known to express higher IL-17 cytokine levels than those from healthy subjects, but the regulatory mechanisms involved are not well understood. We hypothesize that Th-17 regulatory cytokines could modulate IL-17 expression in neutrophils. Peripheral blood neutrophils isolated from asthmatics were stimulated with IL-21, IL-23, and IL-6 cytokines and their ability to produce IL-17A and IL-17F was determined relative to healthy controls. Signal transducer and activator of transcription 3 (STAT3) phosphorylation levels were measured in stimulated neutrophil using flow cytometry. The requirement for STAT3 phosphorylation was determined by blocking its activation using a specific chemical inhibitor. Stimulating asthmatic neutrophils with IL-21, 23, and 6 enhanced the production of IL-17A and IL-17F at significantly higher levels comparatively to healthy controls. Stimulating neutrophils with IL-21, IL-23, and IL-6 cytokines enhanced STAT3 phosphorylation, in all cases. Interestingly, inhibiting STAT3 phosphorylation using a specific chemical inhibitor dramatically blocked the ability of neutrophils to produce IL-17, demonstrating that STAT3 activation is the major factor mediating IL-17 gene expression. These findings suggest that neutrophil infiltration in lungs of severe asthmatics may represent an important source of pro-inflammatory IL-17A and -F cytokines, a production enhanced by Th-17 regulatory cytokines, and thus providing a feedback mechanism that sustains inflammation. Our results suggest that STAT3 pathway could be a potential target for regulating neutrophilic inflammation during severe asthma.

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.

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)

1987-12-31

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.

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.

Mathematics and history: history and analysis epistemology: from exhaustion method to defined integral

Directory of Open Access Journals (Sweden)

Mario Mandrone

2015-06-01

Full Text Available The creation of the calculation (differential, in the terminology of Leibniz, bending in that of Newton is the event that, in the second half of the seventeenth century, marked, in a sense, the transition from classical to modern mathematics. The aim of this work is a historical analysis of the rigor and epistemological question and the "metaphysics" of calculus that takes account of the methods of the ancient (eg. Of Archimedes' method of exhaustion, as well as interpretations of Leibniz and Newton and their successors. The problem of searching for a sure foundation on which to base the calculus, glimpsed by D'Alembert in the theory of limits and taken up by Lagrange to the theory of infinite series, and that the derivative functions, found in Cachy the pioneer of a new way to seek rigor in analysis. The Cauchy setting will be tightened by Weierstrass in the second half of the 800 with the definition of limit, with the epsilon-delta method, which in turn is based on definitions concerning the real numbers. In this sense we speak of "arithmetisation" analysis.         Matematica e storia: storia ed epistemologia dell’analisi: dal metodo  di esaustione  all’integrale  definito La creazione del calcolo (differenziale, nella terminologia leibniziana flessionale in quella di Newton è l’evento che, nella seconda metà del seicento, ha segnato, in un certo senso, il passaggio dalla matematica classica a quella moderna. Obiettivo del presente lavoro è una analisi storica ed epistemologica della questione del rigore e della “metafisica” del calcolo infinitesimale che tenga conto dei metodi degli antichi (ad es.  del metodo di esaustione di Archimede, nonché delle interpretazioni di Leibniz e Newton e dei loro successori. Il problema della ricerca di un fondamento sicuro su cui basare il calcolo infinitesimale, intravisto da D’Alembert nella teoria dei limiti e ripreso da Lagrange con la teoria delle serie infinite e quella delle

Il metodo mitico e i cattivi pensieri

Directory of Open Access Journals (Sweden)

Elio Franzini

2012-05-01

Full Text Available Moving from a definition of his « mythical method», the essay aims to outline the so-called «Philosophy of Art» of Paul Valéry. It sketches a portrait of the French author as an authentic philosopher of phenomenology able to define in a non-abstract way what must be intended with «aesthetics».

Caratterizzazione biomolecolare di Clostridi isolati da latte e formaggi

OpenAIRE

Demarco, Fabiana

2006-01-01

Il latte è una miscela complessa di sostanze di notevole importanza biologica e nutrizionale (proteime, grassi, lattosio, vitamine, sali, etc.) e costituisce, da solo un sistema dietetico bilanciato e capace di favorire la moltiplicazione della flora intestinale simbiotica. E’ ampiamente utilizzato sia tal quale nella preparazione del cibo, sia trasformato, da solo, o in combinazione con altri alimenti. Il formaggio, che rappresenta il più antico e valido metodo conosciuto dall’uomo per co...

Chimica-fisica primo anno

CERN Document Server

Bianchi, U; Volta, L

Termodinamica ; cenni sulla costituzione della materia ; il metodo statistico ; le statistiche di Boltzmann-Maxwell, Bose-Einstein e Fermi-Dirac ; studio termodinamico e statistico del gas perfetto e delle miscele gassose ; i solidi cristallini ; le reazioni chimiche.

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

compared with saline infusion. In addition, C-reactive protein increased 3 h post-rhIL-6 infusion and was further elevated 16 h later compared with saline infusion. rhIL-6 induced increased levels of plasma cortisol and, consequently, an increase in circulating neutrophils and a decrease in the lymphocyte......-alpha, enhances the levels not only of IL-1ra but also of IL-10. Furthermore, IL-6 induces an increase in cortisol and, consequently, in neutrocytosis and late lymphopenia to the same magnitude and with the same kinetics as during exercise, suggesting that muscle-derived IL-6 has a central role in exercise...

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

OpenAIRE

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

1989-01-01

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

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.

Learning on the fly with the analogical method

Directory of Open Access Journals (Sweden)

Zara Mehrnoosh

2016-04-01

Full Text Available Today in Italy 20-25% of students in primary school is reported to have difficulties with mathematical skills, although several researchers have noticed a man’s natural predisposition towards numbers. In the light of this high number of reports becomes therefore necessary to reconsider the didactic context to better support the natural evolution of numerical and mathematical cognition from early childhood. The following article presents the analogical method developed by Camillo Bortolato: non-conceptual didactic path focused on semantic process, subitizing and mental math. Apprendere al volo con il metodo analogicoAd oggi in Italia il 20-25% degli alunni nella scuola primaria viene segnalato per difficoltà nel calcolo, nonostante diversi ricercatori abbiano evidenziato una naturale predisposizione dell’uomo verso la numerosità. Alla luce di questo elevato numero di segnalazioni diviene necessario ripensare il contesto didattico per sostenere al meglio e fin dalla prima infanzia la naturale evoluzione della cognizione numerica e di calcolo. Nel seguente articolo viene presentato il metodo analogico di Camillo Bortolato, un percorso didattico non concettuale attento ai processi semantici, al ruolo del subitizing e del calcolo a mente.

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

International Nuclear Information System (INIS)

Liu Congjiang; Li Fen; Zhang Lei; Liu Jianhua

2008-01-01

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

IFN-γ, IL-4 and IL-13 modulate responsiveness of human airway smooth muscle cells to IL-13

Directory of Open Access Journals (Sweden)

Michoud Marie-Claire

2008-12-01

Full Text Available Abstract Background IL-13 is a critical mediator of allergic asthma and associated airway hyperresponsiveness. IL-13 acts through a receptor complex comprised of IL-13Rα1 and IL-4Rα subunits with subsequent activation of signal transducer and activator of transcription 6 (STAT6. The IL-13Rα2 receptor may act as a decoy receptor. In human airway smooth muscle (HASM cells, IL-13 enhances cellular proliferation, calcium responses to agonists and induces eotaxin production. We investigated the effects of pre-treatment with IL-4, IL-13 and IFN-γ on the responses of HASM cells to IL-13. Methods Cultured HASM were examined for expression of IL-13 receptor subunits using polymerase chain reaction, immunofluorescence microscopy and flow cytometry. Effects of cytokine pre-treatment on IL-13-induced cell responses were assessed by looking at STAT6 phosphorylation using Western blot, eotaxin secretion and calcium responses to histamine. Results IL-13Rα1, IL-4Rα and IL-13Rα2 subunits were expressed on HASM cells. IL-13 induced phosphorylation of STAT6 which reached a maximum by 30 minutes. Pre-treatment with IL-4, IL-13 and, to a lesser degree, IFN-γ reduced peak STAT6 phosphorylation in response to IL-13. IL-13, but not IFN-γ, pre-treatment abrogated IL-13-induced eotaxin secretion. Pre-treatment with IL-4 or IL-13 abrogated IL-13-induced augmentation of the calcium transient evoked by histamine. Cytokine pre-treatment did not affect expression of IL-13Rα1 and IL-4Rα but increased expression of IL-13Rα2. An anti-IL-13Rα2 neutralizing antibody did not prevent the cytokine pre-treatment effects on STAT6 phosphorylation. Cytokine pre-treatment increased SOCS-1, but not SOCS-3, mRNA expression which was not associated with significant increases in protein expression. Conclusion Pre-treatment with IL-4 and IL-13, but not IFN-γ, induced desensitization of the HASM cells to IL-13 as measured by eotaxin secretion and calcium transients to histamine

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.

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.

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.

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

International Nuclear Information System (INIS)

Zhang Chao; Liu Deyi; Hou Guihua; Wang Haodan

2002-01-01

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

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.

The dichotomous pattern of IL-12r and IL-23R expression elucidates the role of IL-12 and IL-23 in inflammation.

Directory of Open Access Journals (Sweden)

Gaëlle Chognard

Full Text Available IL-12 and IL-23 cytokines respectively drive Th1 and Th17 type responses. Yet, little is known regarding the biology of these receptors. As the IL-12 and IL-23 receptors share a common subunit, it has been assumed that these receptors are co-expressed. Surprisingly, we find that the expression of each of these receptors is restricted to specific cell types, in both mouse and human. Indeed, although IL-12Rβ2 is expressed by NK cells and a subset of γδ T cells, the expression of IL-23R is restricted to specific T cell subsets, a small number of B cells and innate lymphoid cells. By exploiting an IL-12- and IL-23-dependent mouse model of innate inflammation, we demonstrate an intricate interplay between IL-12Rβ2 NK cells and IL-23R innate lymphoid cells with respectively dominant roles in the regulation of systemic versus local inflammatory responses. Together, these findings support an unforeseen lineage-specific dichotomy in the in vivo role of both the IL-12 and IL-23 pathways in pathological inflammatory states, which may allow more accurate dissection of the roles of these receptors in chronic inflammatory diseases in humans.

Role of periostin, FENO, IL-13, lebrikzumab, other IL-13 antagonist and dual IL-4/IL-13 antagonist in asthma.

Science.gov (United States)

Agrawal, Swati; Townley, Robert G

2014-02-01

Asthma markedly diminishes quality of life due to limited activity, absences from work or school and hospitalizations. Patients with severe asthma which are not controlled despite taking effective therapy are most in need of new treatment approaches. IL-13 was demonstrated as 'central mediator of allergic asthma'. IL-13 has been implicated in the pathogenesis of asthma, idiopathic pulmonary fibrosis and COPD. IL-13 levels in the sputum and bronchial biopsy samples remain elevated in severe asthma despite the use of inhaled and systemic corticosteroids. Thus, IL-13 is a mediator involved in corticosteroid resistance. Periostin enhances profibrotic TGF-β signaling in subepithelial fibrosis associated with asthma. IL-13 induces bronchial epithelial cells to secrete periostin. Periostin may be a biomarker for Th2 induced airway inflammation. Lebrikizumab is a monoclonal antibody against IL-13. Lebrikizumab improved lung function in asthmatics who were symptomatic despite treatment with long acting beta agonist and inhaled corticosteroids and provided benefit in the treatment of severe uncontrolled asthma. Lebrikizumab block IL-13 signaling through the IL-13Rα1/IL-4Rα receptor. There was a larger reduction in FENO in the high periostin subgroup than in the low periostin subgroup (34.4 vs 4.3%). Serum CCL17, CCL13 and total IgE levels decreased in the lebrikizumab group.

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

Journal of Rehabilitation Research and Development Progress Reports 1994, Volume 32, June 1995

Science.gov (United States)

1995-06-01

May 1993. La misura degli intervalli di attivazione muscolare durante il movimento: un metodo di detezione statistica, Bonato P, D’alessio T...Philadelphia, PA 19107; Division of Medical Sciences. Alfred I. dti Pont Institute, Wilmington, DP. 19803; Olsen Biochemistry Laboratories, South Dakota

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.

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...

IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid arthritis

Science.gov (United States)

Chahbi, Mayssa; Haouami, Youssra; Sfar, Imen; Abdelmoula, Leila; Ben Abdallah, Taieb; Gorgi, Yousr

2018-01-01

Background Interleukin-17 (IL-17), a cytokine mainly secreted by Th17 cells, seems to play a significant role in the pathogenesis of rheumatoid arthritis (RA). Functional genetic polymorphisms in IL-17 and its receptor genes can influence either qualitatively or quantitatively their functions. Therefore, we aimed to study the impact of IL17-A and IL17RC polymorphisms on plasma level of IL-17 and RA susceptibility and severity. Methods In this context, IL-17A*rs2275913 and IL-17RC*rs708567 polymorphisms were investigated together with the quantification of IL17 plasma level in 115 RA patients and 91 healthy control subjects matched in age, sex and ethnic origin. Results There were no statistically significant associations between IL-17A and IL-17RC studied polymorphisms and RA susceptibility. In contrast, IL-17A plasma levels were significantly higher in patients (55.07 pg/ml) comparatively to controls (4.75 pg/ml), p<10E-12. A ROC curve was used to evaluate the performance of plasma IL-17 in detecting RA. Given 100% specificity, the highest sensitivity of plasma IL-17A was 61.7% at a cut-off value of 18.25 pg/ml; p < 10E-21, CI = [0.849–0.939]. Analytic results showed that the IgM-rheumatoid factor and anti-CCP antibodies were significantly less frequent in patients with the IL-17RC*A/A genotype than those carrying *G/G and *G/A genotypes; p = 0.013 and p = 0.015, respectively. Otherwise, IL-17 plasma levels’ analysis showed a significant association with the activity of RA (DAS28≥5.1 = 74.71 pg/ml vs. DAS28<5.1 = 11.96 pg/ml), p<10E-6. Conclusion IL-17A*rs2275913 (G/A) and IL-17RC*rs708567 (G/A) polymorphisms did not seem to influence RA susceptibility in Tunisian population. This result agrees with those reported previously. Plasma IL-17A level seems to be predictive of severe RA occurrence. PMID:29584788

Genetic polymorphism of interleukin-1A (IL-1A), IL-1B, and IL-1 receptor antagonist (IL-1RN) and prostate cancer risk.

Science.gov (United States)

Xu, Hua; Ding, Qiang; Jiang, Hao-Wen

2014-01-01

We aimed to investigate the associations between polymorphisms of interleukin-1A (IL-1A), IL-1B, and IL-1 receptor antagonist (IL-1RN) and prostate cancer (PCa) risk. A comprehensive search for articles of MEDLINE and EMBASE databases and bibliographies of retrieved articles published up to August 3, 2014 was performed. Methodological quality assessment of the trials was based on a standard quality scoring system. The meta-analysis was performed using STATA 12.0. We included 9 studies (1 study for IL-1A, 5 studies for IL-1B, and 3 studies for IL-1RN), and significant association was found between polymorphisms of IL-1B-511 (rs16944) as well as IL-1B-31 (rs1143627) and PCa risk. IL-1B-511 (rs16944) polymorphism was significantly associated with PCa risk in homozygote and recessive models, as well as allele contrast (TT vs CC: OR, 0.74; 95%CI, 0.58-0.94; P=0.012; TT vs TC+CC; OR, 0.79; 95%CI, 0.63-0.98; P=0.033; T vs C: OR, 0.86; 95%CI, 0.77-0.96; P=0.008). The association between IL-1B-31 (rs1143627) polymorphism and PCa risk was weakly significant under a heterozygote model (OR, 1.35; 95%CI, 1.00-1.80; P=0.047). Sequence variants in IL-1B-511 (rs16944) and IL-1B-31 (rs1143627) are significantly associated with PCa risk, which provides additional novel evidence that proinflammatory cytokines and inflammation play an important role in the etiology of PCa.

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.

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.

La prolusione di rocco e le dottrine del processo penale

OpenAIRE

Renzo Orlandi

2015-01-01

L’articolo analizza le conseguenze del pensiero giuridico di Arturo Rocco, dal 1910 nella dottrina di procedura penale, ossia, il metodo tecnico-giuridico (esegesi, sistematica e critica). La dogmatica di procedura pena- le inizia con la monografia di Giovanni Conso, nel 1955. L’insoddisfazione con il tecnicismo giuridico e con la mancanza di maturità scientifica si è manifestata con Carnelutti nel 1946 (Cerenterola), sottolineando le peculiarità strutturali del procedimento penale. In questa...

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.

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...

ELENA MODENA, L'altrOrfeo. Considerazioni analitiche sulla vocalità, Roma, Aracne, 2009

Directory of Open Access Journals (Sweden)

Adriana Guarnieri

2012-11-01

Full Text Available Il volume propone un’indagine sulla vocalità ispirata al «metodo funzionale della voce» di Gisela Rohmert, didatta e fondatrice del Lichtenberger Institut für angewandte Stimmphysiologie, attivo in Germania dal 1982 . Da quell'esperienza – un metodo di pedagogia della voce fondato sullo studio della fisiologia vocale e del «fatto vocale» in quanto evento acustico e stimolo percettivo – Elena Modena ha derivato e illustra in questo libro una sua proposta di «analisi funzionale» della vocalità, storicamente considerata e rivolta, insieme, all’àmbito dell’emissione e a quello dell’ascolto.

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%.

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)

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.

Rapid Methods of Determining Internal Radioactive Contamination; Methodes Rapides Permettant d'Evaluer la Contamination Radioactive Interne; 0411 042b 0414 ; Metodos Rapidos para Determinar la Contaminacion Radiactiva Interna

Energy Technology Data Exchange (ETDEWEB)

Sedlet, J.; Fairman, W. D.; Robinson, J. J. [Industrial Hygiene and Safety Division, Argonne National Laboratory, Argonne, IL (United States)

1965-06-15

, il est possible de l'atteindre. Les emetteurs alpha et les emetteurs beta purs de faible energie presentent la plus grande difficulte du fait que les charges corporelles de ces nucleides doivent ordinairement etre evaluees par une analyse radiochimique du sang ou des excreta. Les auteurs decrivent les separations radiochimiques qui ont ete mises au point et appliquees au Laboratoire national d*Argonne pour doser rapidement ces emetteurs. Le memoire examine d'autre part certains problemes que pose l'obtention de charges corporelles a partir des taux d'excretion, peu apres l'absorption. Pendant ce laps de temps, l'excretion se modifie rapidement et, pour beaucoup de nucleides importants en l'occurrence, a un taux inconnu. Pour les taux d'absorption tres eleves ou tres bas, il n'est pas necessaire de connaitre immediatement la mesure precise des charges corporelles. Cependant, il existe pour chaque radionucleide une dose d'absorption intermediaire pour laquelle il faut pouvoir -determiner sans trop tarder la charge corporelle avec une precision relative, ce qui permet de decider ou non le traitement. Les auteurs examinent les proprietes et les facteurs qui rendent le dosage des elements osteotropes particulierement difficile dans les cas d'accident. (author) [Spanish] Los metodos aplicables en casos de accidente o en situaciones excepcionales tienen que ser suficientemente rapidos y sensibles para proporcionar resultados en plazos que faciliten el tratamiento eficaz de las personas sobreexpuestas. Los plazos disponibles dependeran, en parte, del numero de individuos irradiados. Si se logra obtener en pocas horas resultados utiles, se habra cumplido la funcion primaria de las mediciones rapidas de la carga corporal, que es la de contribuir en toda la medida de lo posible a reducir los danos debidos .a radionuclidos depositados internamente. Los metodos que se citan a continuacion pueden servir para evaluar la contaminacion interna en casos de accidente: recuento gamma y

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

International Nuclear Information System (INIS)

Huang Haifeng; Bi Mingye; Shi Hejian

2009-01-01

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

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

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

International Nuclear Information System (INIS)

Wei Dong; Zhang Xiaolei; Yang Chunxiu; Chen Guanghua

2008-01-01

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

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 .

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.

Fisica del nucleo stelle di neutroni

CERN Document Server

Bernardini, Carlo

1982-01-01

Studio sistematico delle masse nucleari ; energia di legame ; raggi nucleari dai nuclei speculari ; il nucleo in approssimazione di Thomas-Fermi ; introduzione allo scattering : caratterizzazione cinematica degli urti ; la sezione d'urto ; il fattore di forma dei nuclei ; gli atomi u-mesici ; proprieta elettromagnetiche statiche dei nuclei (momenti di multipolo) ; momento di quadrupolo elettrico dei nuclei ; momento d dipolo magnetico dei nuclei ; metodo delle risonanze magnetiche nucleari (NMR) ; misura del fattore giromagnetico e del momento di quadrupolo ; modelli nucleari a particelle indipendenti, il modello a shell ; l'interazione spin-orbita ; il modello a shell e le linee di Schmidt per il momento magnetico dei nuclei con "A" dispari ; nuclei non sferici (deformati) ; stelle di neutroni.

Functional Implications of the IL-23/IL-17 Immune Axis in Schizophrenia.

Science.gov (United States)

Debnath, Monojit; Berk, Michael

2017-12-01

The aetiology of schizophrenia seems to stem from complex interactions amongst environmental, genetic, metabolic, immunologic and oxidative components. Chronic low-grade inflammation has been persistently linked to schizophrenia, and this has primarily been based on the findings derived from Th1/Th2 cytokine balance. While the IL-23/IL-17 axis plays crucial role in the pathogenesis of several immune-mediated disorders, it has remained relatively unexplored in neuropsychiatric disorders. Altered levels of cytokines related to IL-23/IL-17 axis have been observed in schizophrenia patients in a few studies. In addition, other indirect factors known to confer schizophrenia risk like complement activation and altered gut microbiota are shown to modulate the IL-23/IL-17 axis. These preliminary observations provide crucial clues about the functional implications of IL-23/IL-17 axis in schizophrenia. In this review, an attempt has been made to highlight the biology of IL-23/IL-17 axis and its relevance to schizophrenia risk and pathogenesis. Given the pathogenic potential of the IL-23/IL-17 axis, therapeutic targeting of this axis may be a promising approach to benefit patients suffering from this devastating disorder.

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-12p....... The frequencies of the various genotypes for the promoter region of the gene encoding IL-12p40 (IL12B) did not differ between psoriasis patients and controls. No association was observed between the various IL12B promoter genotypes and the LPS-stimulated production of IL-12p70 or IL-12p40 by blood cells. Together......, psoriasis is not associated with a promoter polymorphism in the IL12B gene nor with the production of IL-12p70 by LPS-stimulated blood cells....

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.

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)

Seasonal influenza A/H3N2 virus infection and IL-1Β, IL-10, IL-17, and IL-28 polymorphisms in Iranian population.

Science.gov (United States)

Rogo, Lawal Dahiru; Rezaei, Farhad; Marashi, Seyed Mahdi; Yekaninejad, Mir Saeed; Naseri, Maryam; Ghavami, Nastaran; Mokhtari-Azad, Talat

2016-12-01

Increased blood cytokines is the main immunopathological process that were attributed to severe clinical outcomes in cases of influenza A/H3N2 virus infection. The study was aimed to investigate the polymorphisms of IL-1β, IL-10, IL-17, and IL-28 genes to find the possibility of their association with the clinical outcome of influenza A/H3N2 virus infection among the infected patients in Iran. This is a Case-Control study in which influenza A/H3N2 virus positive confirmed with real-time PCR were the cases. DNA samples from groups were genotyped for polymorphisms in rs16944 (IL-1β), rs1800872 (IL-10), rs2275913 (IL-17), and rs8099917 (IL-28). Confidence interval (95%CI) and Odds ratio (OR) were calculated. IL-17 rs2275913 (GG and AG) were associated with risk of infection with that were statistically significant (P rs16944) (GG) was associated with reduced risk of infection (P < 0.01, OR = 0.46). Genotype GG and GT of IL-10 (rs1800872) were associated with increased risk of infection with influenza A/H3N2 virus (P < 0.05, OR = 2.04-2.58). In addition, IL-28 (rs8099917) genotypes GG (P < 0.05, OR = 0.49) and TG (P < 0.05, OR = 0.59) were associated with reduced risk of ILI symptom while genotype TT (P < 0.01, OR = 4.31) was associated with increased risk of ILI symptom. The results of this study demonstrated that polymorphisms of genes involved in the inflammatory and anti-inflammatory process affect the outcome of disease caused by influenza A/H3N2 virus. Thorough insight on host immune response at the time of influenza A virus infection is required to ensure adequate patient care in the case of feature outbreaks. J. Med. Virol. 88:2078-2084, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Pregnancy, but not the allergic status, influences spontaneous and induced interleukin-1beta (IL-1beta), IL-6, IL-10 and IL-12 responses.

Science.gov (United States)

Amoudruz, Petra; Minang, Jacob Taku; Sundström, Yvonne; Nilsson, Caroline; Lilja, Gunnar; Troye-Blomberg, Marita; Sverremark-Ekström, Eva

2006-09-01

In this study, we investigated how pregnancy influences cytokine production in response to stimulation of the innate and the adaptive immune system, respectively. Peripheral blood mononuclear cells (PBMCs) from allergic (n = 44) and non-allergic (n = 36) women were collected at three time-points: during the third trimester, at delivery and at a non-pregnant state 2 years after delivery. The production of interleukin-1beta (IL-1beta), IL-6, IL-10 and IL-12 was measured by enzyme-linked immunosorbent assay (ELISA) or enzyme-linked immunospot assay (ELISPOT). The spontaneous cytokine production, and the response following stimulation with agents that primarily activate the adaptive part of the immune system [phytohaemagglutinin (PHA), allergen extracts from cat and birch], or lipopolysaccharide (LPS) that activate innate immunity was measured in vitro. There was a significantly higher spontaneous in vitro production of IL-1beta, IL-6 and IL-10 by PBMCs during pregnancy than 2 years after pregnancy, and this was not affected by the allergic status of the women. Conversely, in PHA-stimulated cell cultures there was a lower production of IL-10 and IL-12 during pregnancy than 2 years after pregnancy. LPS-induced IL-6 levels were significantly lower in PBMCs obtained during pregnancy than at 2 years after pregnancy. In addition, we made the interesting observation that in allergic women total immunoglobulin E (IgE) levels were significantly lower 2 years after pregnancy compared to the levels during pregnancy. Taken together, our results indicate that while atopic allergy in women does not have a substantial effect on cytokine production, pregnancy has an obvious effect on the immune system in terms of cytokine production as well as on the total IgE levels.

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.

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.

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.

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...

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

Directory of Open Access Journals (Sweden)

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.

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.

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.

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

International Nuclear Information System (INIS)

Lu Xiaozhuo; Yu Xian

2003-01-01

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

The secreted form of the p40 subunit of interleukin (IL)-12 inhibits IL-23 functions and abrogates IL-23-mediated antitumour effects

Science.gov (United States)

Shimozato, Osamu; Ugai, Shin-ichi; Chiyo, Masako; Takenobu, Hisanori; Nagakawa, Hiroyasu; Wada, Akihiko; Kawamura, Kiyoko; Yamamoto, Hiroshi; Tagawa, Masatoshi

2006-01-01

Interleukin (IL)-23 is a heterodimeric cytokine consisting of a novel p19 molecule and the p40 subunit of IL-12. Since secreted p40 can act as an antagonist for IL-12, we investigated whether p40 also inhibited IL-23-mediated immunological functions. p40 did not induce interferon (IFN)-γ or IL-17 production from splenocytes but impaired IL-23-induced cytokine production by competitive binding to the IL-23 receptors. Furthermore, a mixed population of murine colon carcinoma Colon 26 cells transduced with the p40 gene and those transduced with the IL-23 gene developed tumours in syngenic mice, whereas the IL-23-expressing Colon 26 cells were completely rejected. p40 also suppressed IFN-γ production of antigen-stimulated splenocytes and IL-23-mediated cytotoxic T-lymphocyte activities in the mice that rejected Colon 26 cells expressing IL-23. p40 can thereby antagonize IL-23 and is a possible therapeutic agent for suppression of IL-23 functions. PMID:16423037

IL22/IL-22R pathway induces cell survival in human glioblastoma cells.

Directory of Open Access Journals (Sweden)

Hussein Akil

Full Text Available Interleukin-22 (IL-22 is a member of the IL-10 cytokine family that binds to a heterodimeric receptor consisting of IL-22 receptor 1 (IL-22R1 and IL-10R2. IL-22R expression was initially characterized on epithelial cells, and plays an essential role in a number of inflammatory diseases. Recently, a functional receptor was detected on cancer cells such as hepatocarcinoma and lung carcinoma, but its presence was not reported in glioblastoma (GBM. Two GBM cell lines and 10 primary cell lines established from patients undergoing surgery for malignant GBM were used to investigate the expression of IL-22 and IL-22R by using quantitative RT-PCR, western blotting and confocal microscopy studies. The role of IL-22 in proliferation and survival of GBM cell lines was investigated in vitro by BrdU and ELISA cell death assays. We report herein that the two subunits of the IL-22R complex are expressed on human GBM cells. Their activation, depending on exogenous IL-22, induced antiapoptotic effect and cell proliferation. IL-22 treatment of GBM cells resulted in increased levels of phosphorylated Akt, STAT3 signaling protein and its downstream antiapoptotic protein Bcl-xL and decreased level of phosphorylated ERK1/2. In addition, IL-22R subunits were expressed in all the 10 tested primary cell lines established from GBM tumors. Our results showed that IL-22R is expressed on GBM established and primary cell lines. Depending on STAT3, ERK1/2 and PI3K/Akt pathways, IL-22 induced GBM cell survival. These data are consistent with a potential role of IL-22R in tumorigenesis of GBM. Since endogenous IL-22 was not detected in all studied GBM cells, we hypothesize that IL-22R could be activated by immune microenvironmental IL-22 producing cells.

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.

Il-legitimacy in the eyes of the il-legitimated

DEFF Research Database (Denmark)

Gerstroem, Anna

2013-01-01

The financial crisis has brought il-legitimacy to the center of organizational life in the banking industry. It is unfortunate that little is known about how organizational il-legitimacy is experienced and handled by the people who spend most of their wakening hours at work within...... 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...... an inductive approach and offers an explorative analysis based on an in-depth study of qualitative interviews with 20 members of a bankrupted bank. The analysis shows that in bankers’ narrations, (il)legitimacy is central: as a problem and as a solution. The paper contributes to extant knowledge on (il...

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...

Interleukin (IL)-8 and IL-36γ but not IL-36Ra are related to acrosyringia in pustule formation associated with palmoplantar pustulosis.

Science.gov (United States)

Xiaoling, Y; Chao, W; Wenming, W; Feng, L; Hongzhong, J

2018-06-12

Palmoplantar pustulosis (PPP) is a refractory, nonbacterial impetigo confined to the palms and soles. Its pathogenesis is still obscure, but it may be associated with the large eccrine sweat glands and pores of palmoplantar skin. PPP is considered to be a localized pustular psoriasis. Interleukin (IL)-8, IL-36γ and IL-36Ra play important roles in the pathogenesis of pustular psoriasis, but their role in PPP is unclear. To evaluate IL-8, IL-36γ and IL-36Ra expression in PPP, and their relationship with acrosyringia and pustule formation. mRNA expression was quantified in skin samples from patients with PPP (n = 7), patients with psoriasis vulgaris (PSV; n = 8) and healthy controls (HCs) (n = 6) by reverse-transcription-real-time PCR. Protein expression was characterized by immunohistochemistry (PPP, n = 17; PSV, n = 14; HCs, n = 12). Sweat ducts, including acrosyringia, were stained for epithelial membrane antigen (EMA). IL-8 mRNA and protein were markedly increased in PPP lesions compared with PSV lesions or HC skin. IL-36γ mRNA and protein were significantly more abundant in PPP lesions than in HC skin. IL-36Ra mRNA was significantly overexpressed in PPP lesions compared with HC skin, but there was no difference in IL-36Ra protein between PPP, PSV and HCs. IL-8 was abundantly expressed by neutrophils in PPP pustules, while IL36Ra was localized in the keratinocytes of PPP, PSV and HC skin. IL-36γ and EMA were colocalized in cells surrounding PPP pustules, and IL-36γ was also expressed in sweat duct cells in the dermis. IL-8, IL-36γ and IL-36Ra are overexpressed in PPP lesions. IL-8, IL-36γ and acrosyringia, rather than IL-36Ra, are associated with pustule formation in PPP. © 2018 British Association of Dermatologists.

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....

Analysis of the innovation needs of SME; Analisi della domanda di innovazione delle PMI

Energy Technology Data Exchange (ETDEWEB)

Sabattinin, A; Finelli, A; Rappini, R; Zacchiroli, R. [ENEA, Centro Richerche `E. Clementel`, Bologna (Italy)

1998-12-31

Within an EU financial support (Innovation Relay-Centre IRENE), was set up and tested a method to identify the innovation needs of SMEs. This method, based on firm visits and audits, has proved successful as it is possible to contact firms which find it difficult to approach research centres. These firms are left on their own towards innovation and they cannot evaluate the energetic and environmental implications of introducing a new process or carrying out a new product. The results obtained have highlighted that it is possible to realise a very interesting action of technological transfer starting from the requests for innovation and by means of direct contacts and relationships between firms and research centres. When the SMEs are directly involved they become aware of energetic and environmental problems and, in general, of the engagement that Italy undertook during the conference held in Kyoto. This method is particularly useful to the research centres to which firms can point out and transfer their needs. [Italiano] Nell`ambito di un finanziamento comunitario (Innovation Relay-Centre IRENE), e` stato messo a punto e testato un metodo per l`individuazione della domanda di innovzione delle PMI. Il metodo, basato su visite aziendali e audit, si e` dimostrato particolarmente efficace perche` permette di approcciare anche aziende che hanno grandi difficolta` ad avvicinarsi al mondo della ricerca. Queste imprese sono sole nei confronti dell`innovazione e non sono in grado di valutare quali possano essere le implicazioni, anche energetiche o ambientali, consguenti all`introduzzione di un nuovo processo o alla realizzazione di un nuovo prodotto. I risultati ottenuti hanno evidenziato che, partendo dalla domanda e attraverso il contatto diretto e il dialogo con le strutture di ricerca, e`possibile realizzare interventi di trasferimento tecnologico di grande interesse. Il coinvolgimento diretto permette altresi` di sensibilizzare le PMI sulle problematiche energetiche

Il danno alla persona del lavoratore: il mobbing orizzontale

Directory of Open Access Journals (Sweden)

Riccardo Gentile

2011-12-01

Full Text Available Sommario:1. Il mobbing tra diritto civile e diritto del lavoro – 2. Il fenomeno mobbing: gli studi iniziali e la definizione – 3. Le concrete condotte integranti fattispecie di mobbing – 4. Onere della prova – 5. Il mobbing orizzontale – 6. L’elemento soggettivo di colpevolezza del da­tore di lavoro nella responsabilità ex art. 2087 c.c. per mobbing orizzontale

Associations of vascular endothelial growth factor (VEGF gene and cytokine (IL-1B, IL-4, IL-6, IL-10, TNFA genes combinations with type 2 diabetes mellitus in women

Directory of Open Access Journals (Sweden)

Vladimir Iosifovich Konenkov

2012-09-01

Full Text Available Aim. To study the association between vascular endothelial growth factor (VEGF and cytokine (IL1B, IL4, IL6, IL10 and TNFAgene polymorphism combinations with type 2 diabetes mellitus (T2DM in women. Materials and methods. 374 Caucasian women without carbohydrate metabolism disorders from 23 to 68 years of age and 212 womenwith T2DM from 28 to 69 years of age were included in the study. The combinations of polymorphism А-2578С, С+936Т in VEGFgene with polymorphism in IL1B С-31Т, IL4 С-590Т, IL6 G-174C, IL10 A-592C and А-1082G, TNFA А-238G, A-308G and A-863Cwere studied. Results. Analysis revealed 52 combined genetic variations with different rate of occurrence between diabetic and control groups(р

The role of genetic variation across IL-1β, IL-2, IL-6, and BDNF in antipsychotic-induced weight gain.

Science.gov (United States)

Fonseka, Trehani M; Tiwari, Arun K; Gonçalves, Vanessa F; Lieberman, Jeffrey A; Meltzer, Herbert Y; Goldstein, Benjamin I; Kennedy, James L; Kennedy, Sidney H; Müller, Daniel J

2015-01-01

Antipsychotics with high weight gain-inducing propensities influence the expression of immune and neurotrophin genes, which have been independently related to obesity indices. Thus, we investigated whether variants in the genes encoding interleukin (IL)-1β, IL-2, and IL-6 and brain-derived neurotrophic factor (BDNF) Val66Met are associated with antipsychotic-induced weight gain (AIWG). Nineteen polymorphisms were genotyped using Taqman(®) assays in 188 schizophrenia patients on antipsychotic treatment for up to 14 weeks. Mean weight change (%) from baseline was compared across genotypic groups using analysis of covariance (ANCOVA). Epistatic effects between cytokine polymorphisms and BDNF Val66Met were tested using Model-Based Multifactor Dimensionality Reduction. In European patients, IL-1β rs16944*GA (P = 0.013, Pcorrected = 0.182), IL-1β rs1143634*G (P = 0.001, Pcorrected = 0.014), and BDNF Val66Met (Val/Val, P = 0.004, Pcorrected = 0.056) were associated with greater AIWG, as were IL-1β rs4849127*A (P = 0.049, Pcorrected = 0.784), and IL-1β rs16944*GA (P = 0.012, Pcorrected = 0.192) in African Americans. BDNF Val66Met interacted with both IL-1β rs13032029 (Val/Met+ TT, PPerm = 0.029), and IL-6 rs2069837 (Val/Val+ AA, PPerm = 0.021) in Europeans, in addition to IL-1β rs16944 (Val/Val+ GA, PPerm = 0.006) in African Americans. SNPs across IL-1β and BDNF Val66Met may influence AIWG. Replication of these findings in larger, independent samples is warranted.

Non-Destructive Methods for Determining Burn-Up in Nuclear Fuel; Methodes Non Destructives d'Evaluation du Taux de Combustion dans le Combustible Nucleaire; Metody opredeleniya vygoraniya v yadernom toplive bez razrusheniya obraztsa; Metodos No Destructivos para Determinai el Grado de Combustion de los Elementos Combustibles Nucleares

Energy Technology Data Exchange (ETDEWEB)

McGonnagle, W. J. [Illinois Institute of Technology, Chicago, IL (United States)

1966-02-15

gamma emis par les matieres radioactives qui se forment au cours du processus de fission, en particulier le spectrometre a cristal courbe, le spectrometre Compton magnetique, le spectrometre Compton a coiencidence et le spectrometre a scintillation. Parmi les autres methodes non destructives, on peut citer l'activation de feuilles, la transmission des neutrons, l'analyse par activation, la mesure des rayonnements gamma de capture et la mesure des neutrons instantanes et differes. Le memoire etudie les principes essentiels des differents appareils et procedes ci-dessus, leur precision et leurs limitations. Le memoire presente des methodes non destructives utilisant les isotopes stables produits au cours du processus de fission. Dans les mesures au moyen de ces isotopes, le schema d'irradiation n'a qu'une importance secondaire et le temps de refroidissement ne joue aucun role. De plus, on dispose de donnees nucleaires plus precises sur les produits stables de la fission. Il semble que les plus utiles de tous les isotopes stables produits au cours du processus de fission soient ceux du zirconium, du molybdene, du ruthenium et du neodyme. Le memoire etudie l'interet de ces methodes d'analyse non destructive. (author) [Spanish] Los metodos no destructivos son de gran utilidad para medir cuantitativamente el grado de combustion. El metodo ideal seria el que no requiriese datos especiales sobre los espectros neutrtfni- cos, las irradiaciones precedentes o el tiempo de enfriamiento. Los elementos combustibles irradiados llevan en cierto modo el registro de su grado de combustion. Este registro consiste en el conjunto de los isotopos radiactivos y estables resultantes del proceso de fision. Desgraciadamente, tanto con los metodos no destructivos como con los destructivos el espectro neutronico, las irradiaciones precedentes y el tiempo de enfriamiento influyen sobre dicho registro. Analogamente, la falta de datos nucleares precisos tales como las secciones eficaces nucleares

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

Directory of Open Access Journals (Sweden)

Maida-Claros Rolando

2007-12-01

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

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.

SUI CODICI UNIDIREZIONALI

Directory of Open Access Journals (Sweden)

Luca Tallini

1992-04-01

Full Text Available Oltre ad una breve descrizione della problematica sui codici Unidirezionali è qui data la dimostrazione di una congettura di S. Al-Bassan e B. Bose che interviene nella teoria dei suddetti autori, sulla costruzione di codici ottimali nella classe dei codici bilanciati che si ottengono con il metodo della complementazione di Knuth.

TEMPI DI TRAGITTO DELLE ONDE P* E SPESSORE DELLO STRATO DEL GRANITO NELL'ITALIA CENTRALE

Directory of Open Access Journals (Sweden)

L. Marcelli

1951-06-01

Full Text Available Proseguendo lo studio del terremoto del Gran Sasso d'Italia del5 settembre 1950 si rilevano alcune caratteristiche sismiche dell'Italiacentrale.Si determina la profondità ipocentrale con il metodo dell'angolodi emergenza. Indi si costruisce la dromocrona delle P* e si calcolalo spessore dello strato del granito relativamente alla zona.

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.

Structural Characterisation Reveals Mechanism of IL-13-Neutralising Monoclonal Antibody Tralokinumab as Inhibition of Binding to IL-13Rα1 and IL-13Rα2.

Science.gov (United States)

Popovic, B; Breed, J; Rees, D G; Gardener, M J; Vinall, L M K; Kemp, B; Spooner, J; Keen, J; Minter, R; Uddin, F; Colice, G; Wilkinson, T; Vaughan, T; May, R D

2017-01-20

Interleukin (IL)-13 is a pleiotropic T helper type 2 cytokine frequently associated with asthma and atopic dermatitis. IL-13-mediated signalling is initiated by binding to IL-13Rα1, which then recruits IL-4Rα to form a heterodimeric receptor complex. IL-13 also binds to IL-13Rα2, considered as either a decoy or a key mediator of fibrosis. IL-13-neutralising antibodies act by preventing IL-13 binding to IL-13Rα1, IL-4Rα and/or IL-13Rα2. Tralokinumab (CAT-354) is an IL-13-neutralising human IgG4 monoclonal antibody that has shown clinical benefit in patients with asthma. To decipher how tralokinumab inhibits the effects of IL-13, we determined the structure of tralokinumab Fab in complex with human IL-13 to 2 Å resolution. The structure analysis reveals that tralokinumab prevents IL-13 from binding to both IL-13Rα1 and IL-13Rα2. This is supported by biochemical ligand-receptor interaction assay data. The tralokinumab epitope is mainly composed of residues in helices D and A of IL-13. It is mostly light chain complementarity-determining regions that are driving paratope interactions; the variable light complementarity-determining region 2 plays a key role by providing residue contacts for a network of hydrogen bonds and a salt bridge in the core of binding. The key residues within the paratope contributing to binding were identified as Asp50, Asp51, Ser30 and Lys31. This study demonstrates that tralokinumab prevents the IL-13 pharmacodynamic effect by binding to IL-13 helices A and D, thus preventing IL-13 from interacting with IL-13Rα1 and IL-13Rα2. Copyright © 2016 AstraZeneca. Published by Elsevier Ltd.. All rights reserved.

Association study of IL10 and IL23R-IL12RB2 in Iranian patients with Behçet's disease.

Science.gov (United States)

Xavier, Joana M; Shahram, Farhad; Davatchi, Fereydoun; Rosa, Alexandra; Crespo, Jorge; Abdollahi, Bahar Sadeghi; Nadji, Abdolhadi; Jesus, Gorete; Barcelos, Filipe; Patto, José Vaz; Shafiee, Niloofar Mojarad; Ghaderibarim, Fahmida; Oliveira, Sofia A

2012-08-01

Independent replication of the findings from genome-wide association studies (GWAS) remains the gold standard for results validation. Our aim was to test the association of Behçet's disease (BD) with the interleukin-10 gene (IL10) and the IL-23 receptor-IL-12 receptor β2 (IL23R-IL12RB2) locus, each of which has been previously identified as a risk factor for BD in 2 different GWAS. Six haplotype-tagging single-nucleotide polymorphisms (SNPs) in IL10 and 42 in IL23R-IL12RB2 were genotyped in 973 Iranian patients with BD and 637 non-BD controls. Population stratification was assessed using a panel of 86 ancestry-informative markers. Subtle evidence of population stratification was found in our data set. In IL10, rs1518111 was nominally associated with BD before and after adjustment for population stratification (odds ratio [OR] for T allele 1.20, 95% confidence interval [95% CI] 1.02-1.40, unadjusted P [P(unadj) ] = 2.53 × 10(-2) ; adjusted P [P(adj) ] = 1.43 × 10(-2) ), and rs1554286 demonstrated a trend toward association (P(unadj) = 6.14 × 10(-2) ; P(adj) = 3.21 × 10(-2) ). Six SNPs in IL23R-IL12RB2 were found to be associated with BD after Bonferroni correction for multiple testing, the most significant of which were rs17375018 (OR for G allele 1.51, 95% CI 1.27-1.78, P(unadj) = 1.93 × 10(-6) ), rs7517847 (OR for T allele 1.48, 95% CI 1.26-1.74, P(unadj) = 1.23 × 10(-6) ), and rs924080 (OR for T allele 1.29, 95% CI 1.20-1.39, P = 1.78 × 10(-5) ). SNPs rs10489629, rs1343151, and rs1495965 were also significantly associated with BD in all tests performed. Results of meta-analyses of our data combined with data from other populations further confirmed the role of rs1518111, rs17375018, rs7517847, and rs924080 in the risk of BD, but no epistatic interactions between IL10 and IL23R-IL12RB2 were detected. Results of imputation analysis highlighted the importance of IL23R regulatory regions in the susceptibility to BD. These findings independently confirm

Clinical significance of determination of changes in serum hs-CRP, IL-6, IL-10, and IL-18 levels after treatment in patients with acute conjunctivitis

International Nuclear Information System (INIS)

Liu Jun

2007-01-01

Objective: To study the clinical significance of changes of serum hs-CRP, IL-6, IL-10 and IL-18 levels in patients with acute conjunctivitis after treatment. Methods: Serum IL-6, IL-10 (with RIA) hs-CRP (with Immuno-turbidity) and IL-18 (with ELISA) levels were measured in 38 patients with acute conjunctivitis both before and after treatment as well as in 35 controls. Results: The serum hs-CRP, IL-6, IL-10 and IL-18 levels in the patients before treatment were significantly higher than those in the controls (P 0.05). Conclusion: Measurement of the changes of serum hs-CRP, IL-6, IL-10 and IL-18 levels after treatment might be inportant for outcome prediction in patients with acute conjunctivitis. (authors)

IL-17 mediates immunopathology in the absence of IL-10 following Leishmania major infection.

Directory of Open Access Journals (Sweden)

Claudia Gonzalez-Lombana

2013-03-01

Full Text Available Leishmaniasis, resulting from infection with the protozoan parasite Leishmania, consists of a wide spectrum of clinical manifestations, from healing cutaneous lesions to fatal visceral infections. A particularly severe form of cutaneous leishmaniasis, termed mucosal leishmaniasis, exhibits decreased IL-10 levels and an exaggerated inflammatory response that perpetuates the disease. Using a mouse model of leishmaniasis, we investigated what cytokines contribute to increased pathology when IL-10-mediated regulation is absent. Leishmania major infected C57BL/6 mice lacking IL-10 regulation developed larger lesions than controls, but fewer parasites. Both IFN-γ and IL-17 levels were substantially elevated in mice lacking the capacity to respond to IL-10. IFN-γ promoted an increased infiltration of monocytes, while IL-17 contributed to an increase in neutrophils. Surprisingly, however, we found that IFN-γ did not contribute to increased pathology, but instead regulated the IL-17 response. Thus, blocking IFN-γ led to a significant increase in IL-17, neutrophils and disease. Similarly, the production of IL-17 by cells from leishmaniasis patients was also regulated by IL-10 and IFN-γ. Additional studies found that the IL-1 receptor was required for both the IL-17 response and increased pathology. Therefore, we propose that regulating IL-17, possibly by downregulating IL-1β, may be a useful approach for controlling immunopathology in leishmaniasis.

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

Science.gov (United States)

Cayrol, Corinne; Girard, Jean-Philippe

2018-01-01

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

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.

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

Directory of Open Access Journals (Sweden)

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.

IL-25 or IL-17E protects against high-fat diet-induced hepatic steatosis in mice dependent upon IL-13 activation of STAT6

Science.gov (United States)

IL-25 is a member of IL-17 cytokine family and has immune-modulating activities. The role of IL-25 in maintaining lipid metabolic homeostasis remains unknown. Here, we investigated the effects of exogenous IL-25 or deficiency of IL-25 on lipid accumulation in the liver. Mice were injected with IL-25...

The IL-17F/IL-17RC Axis Promotes Respiratory Allergy in the Proximal Airways

Directory of Open Access Journals (Sweden)

Antonella De Luca

2017-08-01

Full Text Available The interleukin 17 (IL-17 cytokine and receptor family is central to antimicrobial resistance and inflammation in the lung. Mice lacking IL-17A, IL-17F, or the IL-17RA subunit were compared with wild-type mice for susceptibility to airway inflammation in models of infection and allergy. Signaling through IL-17RA was required for efficient microbial clearance and prevention of allergy; in the absence of IL-17RA, signaling through IL-17RC on epithelial cells, predominantly by IL-17F, significantly exacerbated lower airway Aspergillus or Pseudomonas infection and allergic airway inflammation. In contrast, following infection with the upper respiratory pathogen Staphylococcus aureus, the IL-17F/IL-17RC axis mediated protection. Thus, IL-17A and IL-17F exert distinct biological effects during pulmonary infection; the IL-17F/IL-17RC signaling axis has the potential to significantly worsen pathogen-associated inflammation of the lower respiratory tract in particular, and should be investigated further as a therapeutic target for treating pathological inflammation in the lung.

Il metodo della fisica e le problematiche della biologia

Directory of Open Access Journals (Sweden)

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.

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.

Lacrimal gland-derived IL-22 regulates IL-17-mediated ocular mucosal inflammation

Science.gov (United States)

Ji, Yong Woo; Mittal, Sharad K.; Hwang, Ho Sik; Chang, Eun-Ju; Lee, Joon H.; Seo, Yuri; Yeo, Areum; Noh, Hyemi; Lee, Hye Sun; Chauhan, Sunil K.; Lee, Hyung Keun

2016-01-01

Inflammatory damage of mucosal surface of the eye is a hallmark of dry eye disease (DED), and in severe cases can lead to significant discomfort, visual impairment, and blindness. DED is a multifactorial autoimmune disorder with a largely unknown pathogenesis. Using a cross-sectional patient study and a well-characterized murine model of DED, herein we investigated the immunoregulatory function of interleukin-22 (IL-22) in the pathogenesis of DED. We found that IL-22 levels were elevated in lacrimal fluids of DED patients and inversely correlated with severity of disease. Acinar cells of the lacrimal glands, not inflammatory immune cells, are the primary source of IL-22, which suppresses inflammation in ocular surface epithelial cells upon desiccating stress. Moreover, loss of function analyses using IL-22 knock-out mice demonstrated that IL-22 is essential for suppression of ocular surface infiltration of Th17 cells and inhibition of DED induction. Our novel findings elucidate immunoregulatory function of lacrimal gland-derived IL-22 in inhibiting IL-17-mediated ocular surface epitheliopathy in DED thus making IL-22 a new relevant therapeutic target. PMID:28051088

Extracellular Neutrophil Proteases Are Efficient Regulators of IL-1, IL-33, and IL-36 Cytokine Activity but Poor Effectors of Microbial Killing.

Science.gov (United States)

Clancy, Danielle M; Sullivan, Graeme P; Moran, Hannah B T; Henry, Conor M; Reeves, Emer P; McElvaney, Noel G; Lavelle, Ed C; Martin, Seamus J

2018-03-13

Neutrophil granule proteases are thought to function as anti-microbial effectors, cooperatively hydrolyzing microorganisms within phagosomes, or upon deployment into the extracellular space. However, evidence also suggests that neutrophil proteases play an important role in the coordination and escalation of inflammatory reactions, but how this is achieved has been obscure. IL-1 family cytokines are important initiators of inflammation and are typically released via necrosis but require proteolytic processing for activation. Here, we show that proteases liberated from activated neutrophils can positively or negatively regulate the activity of six IL-1 family cytokines (IL-1α, IL-1β, IL-33, IL-36α, IL-36β, and IL-36γ) with exquisite sensitivity. In contrast, extracellular neutrophil proteases displayed very poor bactericidal activity, exhibiting 100-fold greater potency toward cytokine processing than bacterial killing. Thus, in addition to their classical role as phagocytes, neutrophils play an important immunoregulatory role through deployment of their granule proteases into the extracellular space to process multiple IL-1 family cytokines. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

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

Role of the IL-12/IL-35 balance in patients with Sjögren syndrome.

Science.gov (United States)

Fogel, Olivier; Rivière, Elodie; Seror, Raphaèle; Nocturne, Gaetane; Boudaoud, Saida; Ly, Bineta; Gottenberg, Jacques-Eric; Le Guern, Véronique; Dubost, Jean-Jacques; Nititham, Joanne; Taylor, Kimberly E; Chanson, Philippe; Dieudé, Philippe; Criswell, Lindsey A; Jagla, Bernd; Thai, Alice; Mingueneau, Michael; Mariette, Xavier; Miceli-Richard, Corinne

2017-09-12

An interferon signature is involved in the pathogenesis of primary Sjögren syndrome (pSS), but whether the signature is type 1 or type 2 remains controversial. Mouse models and genetic studies suggest the involvement of T H 1 and type 2 interferon pathways. Likewise, polymorphisms of the IL-12A gene (IL12A), which encodes for IL-12p35, have been associated with pSS. The IL-12p35 subunit is shared by 2 heterodimers: IL-12 and IL-35. We sought to confirm genetic association of the IL12A polymorphism and pSS and elucidate involvement of the IL-12/IL-35 balance in patients with pSS by using functional studies. The genetic study involved 673 patients with pSS from 2 French pSS cohorts and 585 healthy French control subjects. Functional studies were performed on sorted monocytes, irrespective of whether they were stimulated. IL12A mRNA expression and IL-12 and IL-35 protein levels were assessed by using quantitative RT-PCR and ELISA and a multiplex kit for IL-35 and IL-12, respectively. We confirmed association of the IL12A rs485497 polymorphism and pSS and found an increased serum protein level of IL-12p70 in patients with pSS carrying the risk allele (P = .016). Serum levels of IL-12p70 were greater in patients than control subjects (P = .0001), especially in patients with more active disease (P = .05); conversely, IL-35 levels were decreased in patients (P = .0001), especially in patients with more active disease (P = .05). In blood cellular subsets both IL12p35 and EBV-induced gene protein 3 (EBI3) mRNAs were detected only in B cells, with a trend toward a lower level among patients with pSS. Our findings emphasize involvement of the IL-12/IL-35 balance in the pathogenesis of pSS. Serum IL-35 levels were associated with low disease activity, in contrast with serum IL-12p70 levels, which were associated with more active disease. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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.

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

International Nuclear Information System (INIS)

Sun Baoyi; Li Jun; Zhang Jiyun

2004-01-01

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

Preliminary study for the determination of heavy metal in ground samples by GF-ASS Zeeman; Studio preliminare per la determinazione di metalli pesanti in campioni di suolo mediante analisi GF-AAS Zeeman

Energy Technology Data Exchange (ETDEWEB)

Casabianca, T.; Bitonte, R.; Epifani, M.; Ubaldi, C. [ENEA, Divisione Tecnologie Ingegneria e Servizi Ambientali, Centro Ricerche Trisaia, MT (Italy)

2001-07-01

In the framework of SIMOA project have been investigated methods to evaluate the level of soil contamination due to heavy metals. In this wok, it is discussed a procedure to measure topsoil bioavailable fraction of seven heavy metals (Cd, Cu, Pb, Ni, Cr, Hg). The adopted procedure is based on acid digestion followed by instrumental detection by means of graphite furnace atomic-absorption spectrophotometry (GFAAS) using Zeeman effect to reduce background contribution. Details of samples preparation and analysis, experimental setup optimization and statistical data analysis are presented, together with a discussion on method accuracy and data interpretation. [Italian] Nell'ambito del progetto SIMOA (Sistema Integrato di Monitoraggio Ambientale) per il monitoraggio ambientale nel bacino del Basento (Regione Basilicata, Italia), vengono investigati i metodi per il controllo dei livelli di inquinamento del suolo da parte di metalli pesanti. Nel presente lavoro viene proposta una procedura per determinare il livello di concentrazione della frazione biodisponibile di sette metalli pesanti (Cadmio, Rame, Piombo, Nickel, Cromo, Mercurio) in campion di suolo superficiale. Il metodo e' basato su di un trattamento di digestione acida in forno a microonde cui segue la rivelazione strumentale mediante spettrofotometria di assorbimento atomico in fornetto di grafite (GFAAS) con effetto Zeeman per la correzione del fondo. Si descrivono in dettaglio le fasi di preparazione dei campioni, la metodologia di misura e l'analisi statistica dei dati, oltre ad una discussione sull'attendibilita' del metodo e sui futuri sviluppi.

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...

[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.

Commensal bacteria and MAMPs are necessary for stress-induced increases in IL-1β and IL-18 but not IL-6, IL-10 or MCP-1.

Directory of Open Access Journals (Sweden)

Thomas Maslanik

Full Text Available Regular interactions between commensal bacteria and the enteric mucosal immune environment are necessary for normal immunity. Alterations of the commensal bacterial communities or mucosal barrier can disrupt immune function. Chronic stress interferes with bacterial community structure (specifically, α-diversity and the integrity of the intestinal barrier. These interferences can contribute to chronic stress-induced increases in systemic IL-6 and TNF-α. Chronic stress, however, produces many physiological changes that could indirectly influence immune activity. In addition to IL-6 and TNF-α, exposure to acute stressors upregulates a plethora of inflammatory proteins, each having unique synthesis and release mechanisms. We therefore tested the hypothesis that acute stress-induced inflammatory protein responses are dependent on the commensal bacteria, and more specifically, lipopolysaccharide (LPS shed from Gram-negative intestinal commensal bacteria. We present evidence that both reducing commensal bacteria using antibiotics and neutralizing LPS using endotoxin inhibitor (EI attenuates increases in some (inflammasome dependent, IL-1 and IL-18, but not all (inflammasome independent, IL-6, IL-10, and MCP-1 inflammatory proteins in the blood of male F344 rats exposed to an acute tail shock stressor. Acute stress did not impact α- or β- diversity measured using 16S rRNA diversity analyses, but selectively reduced the relative abundance of Prevotella. These findings indicate that commensal bacteria contribute to acute stress-induced inflammatory protein responses, and support the presence of LPS-mediated signaling in stress-evoked cytokine and chemokine production. The selectivity of the commensal bacteria in stress-evoked IL-1β and IL-18 responses may implicate the inflammasome in this response.

Influence of the IL-1Ra gene polymorphism on in vivo synthesis of IL-1Ra and IL-1beta after live yellow fever vaccination.

Science.gov (United States)

Hacker, U T; Erhardt, S; Tschöp, K; Jelinek, T; Endres, S

2001-09-01

The inflammatory response in infectious and autoimmune diseases is regulated by the balance between pro- and anti-inflammatory cytokines. The IL-1 complex contains polymorphic genes coding for IL-1alpha, IL-1beta and IL-1Ra. The IL-1Ra (variable number of tanden repeat) VNTR polymorphism has been shown to influence the capacity to produce IL-1beta and IL-1Ra after in vitro stimulation. Allele 2 of this polymorphism is associated with a number of inflammatory diseases. To determine the impact of the IL-1Ra polymorphism on in vivo human cytokine synthesis, we used a yellow fever vaccination model for the induction of cytokine synthesis in healthy volunteers. Two different yellow fever vaccines were used. After administration of the RKI vaccine (34 volunteers), plasma TNF-alpha concentration increased from 13.4 +/- 0.9 pg/ml to 23.3 +/- 1.1 pg/ml (P < 0.001), and plasma IL-1Ra concentration increased from 308 +/- 25 pg/ml to 1019 +/- 111 pg/ml (P < 0.001), on day 2. Using Stamaril vaccine, no increase in the plasma concentrations of either TNF-alpha or IL-1Ra could be detected (n = 17). Only the RKI vaccine induced TNF-alpha synthesis after in vitro stimulation of MNC. Carriers of allele 2 of the IL-1Ra polymorphism had increased baseline concentrations of IL-1Ra (350 +/- 32 pg/ml) compared with non-carriers (222 +/- 18 pg/ml, P < 0.001), and decreased concentrations of IL-1beta (0.9 +/- 0.2 pg/ml for carriers versus 2.8 +/- 0.7 pg/ml for non-carriers, P = 0.017). After yellow fever vaccination (RKI vaccine), no significant differences in the increase of IL-1Ra plasma levels were detected between carriers and non-carriers of allele 2 of the IL-1Ra gene polymorphism. This is the first study to examine the influence of this genetic polymorphism on in vivo-induced human IL-1beta and IL-1Ra synthesis. Baseline concentrations of IL-1Ra and IL-1beta were significantly influenced by the IL-1Ra polymorphism. No influence of the IL-1Ra polymorphism on the in vivo

Quam maximis potest itineribus: andata e ritorno della costruzione tra immagine e modello nello spazio grafico della geometria descrittiva

Directory of Open Access Journals (Sweden)

Matteo Ballarin

2012-06-01

Full Text Available Il contributo testimonia una strategia d'insegnamento congiunto del rilievo architettonico, della geometria descrittiva e del disegno digitale concepita come un viaggio di andata e ritorno tra immagine e modello. Iniziando dalla fotogrammetria elementare e dalle tecniche di foto-modellazione offerte da software (gratuiti e dotati di un'interfaccia sufficientemente  intuitiva si possono poi introdurre – col metodo di Monge – le tecniche del rilievo topografico, giungendo alla costruzione interdefinita di un unico modello digitale degli oggetti del rilievo. Il circolo didattico si chiude poi costruendo rappresentazioni tabulari tradizionali dei modelli.

IL-15 deficient tax mice reveal a role for IL-1α in tumor immunity.

Directory of Open Access Journals (Sweden)

Daniel A Rauch

Full Text Available IL-15 is recognized as a promising candidate for tumor immunotherapy and has been described as both a promoter of cancer and a promoter of anti-cancer immunity. IL-15 was discovered in cells transformed by HTLV-1, the etiologic agent of adult T cell leukemia/lymphoma (ATL and the human retrovirus that carries the Tax oncogene. We have developed the TAX-LUC mouse model of ATL in which Tax expression drives both malignant transformation and luciferase expression, enabling non-invasive imaging of tumorigenesis in real time. To identify the role of IL-15 in spontaneous development of lymphoma in vivo, an IL-15(-/- TAX-LUC strain was developed and examined. The absence of IL-15 resulted in aggressive tumor growth and accelerated mortality and demonstrated that IL-15 was not required for Tax-mediated lymphoma but was essential for anti-tumor immunity. Further analysis revealed a unique transcriptional profile in tumor cells that arise in the absence of IL-15 that included a significant increase in the expression of IL-1α and IL-1α-regulated cytokines. Moreover, anti-IL-1α antibodies and an IL-1 receptor antagonist (Anakinra were used to interrogate the potential of IL-1α targeted therapies in this model. Taken together, these findings identify IL-15 and IL-1α as therapeutic targets in lymphoma.

Pro-inflammatory signaling by IL-10 and IL-22: bad habit stirred up by interferons ?

Directory of Open Access Journals (Sweden)

Heiko eMühl

2013-02-01

Full Text Available Interleukin (IL-10 and IL-22 are key members of the IL-10 cytokine family that share characteristic properties such as defined structural features, usage of IL-10R2 as one receptor chain, and activation of signal transducer and activator of transcription (STAT-3 as dominant signaling mode. IL-10, formerly known as cytokine synthesis inhibitory factor, is key to deactivation of monocytes/macrophages and dendritic cells. Accordingly, pre-clinical studies document its anti-inflammatory capacity. However, the outcome of clinical trials assessing the therapeutic potential of IL-10 in prototypic inflammatory disorders has been disappointing. In contrast to IL-10, IL-22 acts primarily on non-leukocytic cells, in particular epithelial cells of intestine, skin, liver, and lung. STAT3-driven proliferation, anti-apoptosis, and anti-microbial tissue protection is regarded a principal function of IL-22 at host/environment interfaces. In this hypothesis article, hidden/underappreciated pro-inflammatory characteristics of IL-10 and IL-22 are outlined and related to cellular priming by type I interferon. It is tempting to speculate that an inherent inflammatory potential of IL-10 and IL-22 confines their usage in tissue protective therapy and beyond that determines in some patients efficacy of type I interferon treatment.

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

IL-10 and IL-27 producing dendritic cells capable of enhancing IL-10 production of T cells are induced in oral tolerance.

Science.gov (United States)

Shiokawa, Aya; Tanabe, Kosuke; Tsuji, Noriko M; Sato, Ryuichiro; Hachimura, Satoshi

2009-06-30

Oral tolerance is a key feature of intestinal immunity, generating systemic tolerance to ingested antigens (Ag). Dendritic cells (DC) have been revealed as important immune regulators, however, the precise role of DC in oral tolerance induction remains unclear. We investigated the characteristics of DC in spleen, mesenteric lymph node (MLN), and Peyer's patch (PP) after oral Ag administration in a TCR-transgenic mouse model. DC from PP and MLN of tolerized mice induced IL-10 production but not Foxp3 expression in cocultured T cells. IL-10 production was markedly increased after 5-7-day Ag administration especially in PP DC. On the other hand, IL-27 production was increased after 2-5-day Ag administration. CD11b(+) DC, which increased after ingestion of Ag, prominently expressed IL-10 and IL-27 compared with CD11b(-) DC. These results suggest that IL-10 and IL-27 producing DC are increased by interaction with antigen specific T cells in PP, and these DC act as an inducer of IL-10 producing T cells in oral tolerance.

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.

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

Servio e l’analogia

Directory of Open Access Journals (Sweden)

Maria-Luisa Delvigo

2010-11-01

Full Text Available Questo articolo analizza dettagliatamente Serv. ad Georg. 4, 219 (cioè lo scolio relativo al passo in cui Virgilio tratta la presunta partecipazione delle api allo spirito divino. Qui Servio Danielino affronta il problema della coerenza filosofica di Virgilio (cfr. ad Aen. 10, 467 dove sono discussi da Servio i diversi influssi filosofici sull’opera virgiliana, difendendo il poeta da chi lo accusava di non manifestare in questi versi fedeltà all’epicureismo. Servio, da parte sua, ricollega il passo in questione al discorso di Anchise nel VI dell’Eneide e sottolinea i legami con Lucrezio e il metodo epicureo, evidenziando l’uso virgiliano dell’analogia e mostrando ancora una volta uno spiccato interesse per la scienza epicurea.

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.

Il paesaggio dell’architettura

Directory of Open Access Journals (Sweden)

Paolo Zermani

2015-11-01

Full Text Available l saggio si articola come un’itinerario tra alcuni progetti italiani proposti come “occasioni di applicazione di un modo d’intendere l’architettura nel rapporto con il paesaggio smarrito, che cambia, ma potrebbe custodire ancora i valori di ciò che Heidegger definiva il “soggiorno”: la riconoscibilità intesa come misura”. Le architetture, come strumenti di conoscenza dello spazio, entrano nel paesaggio per diventarne speciali “misuratori”.Partendo dai luoghi del paesaggio padano, Noceto, con il Nuovo Municipio, con la minimale Cappella della Madonna, con il Padiglione privato, e Varano, con la Casa dal grande occhio spalancato sul bosco, alle terre umbre, con la Chiesa ed il Centro Parrocchiale di Perugia ed il Cimitero di Sansepolcro, si propone un percorso di ricerca di una identità dell’architettura italiana contemporanea nella dimensione paesaggistica. 

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

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

IL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced Central IL-6 trans-Signaling.

Science.gov (United States)

Timper, Katharina; Denson, Jesse Lee; Steculorum, Sophie Marie; Heilinger, Christian; Engström-Ruud, Linda; Wunderlich, Claudia Maria; Rose-John, Stefan; Wunderlich, F Thomas; Brüning, Jens Claus

2017-04-11

Interleukin (IL)-6 engages similar signaling mechanisms to leptin. Here, we find that central application of IL-6 in mice suppresses feeding and improves glucose tolerance. In contrast to leptin, whose action is attenuated in obesity, the ability of IL-6 to suppress feeding is enhanced in obese mice. IL-6 suppresses feeding in the absence of neuronal IL-6-receptor (IL-6R) expression in hypothalamic or all forebrain neurons of mice. Conversely, obese mice exhibit increased soluble IL-6R levels in the cerebrospinal fluid. Blocking IL-6 trans-signaling in the CNS abrogates the ability of IL-6 to suppress feeding. Furthermore, gp130 expression is enhanced in the paraventricular nucleus of the hypothalamus (PVH) of obese mice, and deletion of gp130 in the PVH attenuates the beneficial central IL-6 effects on metabolism. Collectively, these experiments indicate that IL-6 trans-signaling is enhanced in the CNS of obese mice, allowing IL-6 to exert its beneficial metabolic effects even under conditions of leptin resistance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

IL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced Central IL-6 trans-Signaling

Directory of Open Access Journals (Sweden)

Katharina Timper

2017-04-01

Full Text Available Interleukin (IL-6 engages similar signaling mechanisms to leptin. Here, we find that central application of IL-6 in mice suppresses feeding and improves glucose tolerance. In contrast to leptin, whose action is attenuated in obesity, the ability of IL-6 to suppress feeding is enhanced in obese mice. IL-6 suppresses feeding in the absence of neuronal IL-6-receptor (IL-6R expression in hypothalamic or all forebrain neurons of mice. Conversely, obese mice exhibit increased soluble IL-6R levels in the cerebrospinal fluid. Blocking IL-6 trans-signaling in the CNS abrogates the ability of IL-6 to suppress feeding. Furthermore, gp130 expression is enhanced in the paraventricular nucleus of the hypothalamus (PVH of obese mice, and deletion of gp130 in the PVH attenuates the beneficial central IL-6 effects on metabolism. Collectively, these experiments indicate that IL-6 trans-signaling is enhanced in the CNS of obese mice, allowing IL-6 to exert its beneficial metabolic effects even under conditions of leptin resistance.

Quantitative prediction of strong motion for a potential earthquake fault

Directory of Open Access Journals (Sweden)

B. CHOUET

1977-06-01

Full Text Available RIASSUNTO. - Questa nota descrive un nuovo metodo per calcolare le registrazioni
accelerografìehe per una data regione sismica in base alle leggi fisiche
usando le informazioni relative alla tettonica ed alle proprietà fisiche della faglia
sismica.
Il metodo si basa su di un nuovo modello sismico, chiamato « modello
b a r r i e r a » , caratterizzato da cinque parametri focali: lunghezza della faglia,
larghezza, scorrimento massimo, velocità di rottura ed intervallo di barriera.
I primi tre parametri possono essere vincolati dalla tettonica a placche, il
quarto parametro è approssimativamente una costante. Il parametro più importante,
che controlla l'accelerazione del terremoto, è l'ultimo, l'intervallo « barriera ».
Vi sono tre metodi per valutare 1' « intervallo barriera » per una data
regione sismica: 1 misurazione in superficie dello scorrimento attraverso fratture
di faglia; 2 creazione di un modello che si adatti all'osservazione di
campi vicini e lontani; 5 una legge che regoli i dati per i piccoli terremoti nella
regione.
Gli intervalli barriera sono stati valutati per una dozzina di terremoti e
per quattro regioni sismiche, per mezzo dei tre metodi suindicati. I risultati
preliminari ottenuti per la California suggeriscono che l'intervallo barriera
possa essere determinato quando sia dato il massimo scorrimento. La relazione
tra l'intervallo barriera ed il massimo scorrimento varia da una regione sismica
all'altra. Ad esempio, l'intervallo appare insolitamente lungo per Kilanea (Hawaii,
il che può spiegare perché traccia di forte scorrimento del terreno sia stata
osservata soltanto nell'area epicentrale del terremoto delle Isole Hawaii del 29
novembre 1975.

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

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)

Alternative refrigerants performance in plate heat condenser for air conditioning; Scambiatori compatti per il condizionamento ambientale

Energy Technology Data Exchange (ETDEWEB)

Boccardi, G.; Celata, G.P.; Marchesi Donati, F. [ENEA, Rome (Italy). Inst. of Thermal-Fluid Dynamics; Cumo, M. [Rome Univ. La Sapienza, Rome (Italy). Dept. of Nuclear Engineering and Energy Conversion; Gerosa, A. [Rome Univ. Tor Vergata, Rome (Italy). Dept. of Mechanical Engineering; Zorzin, A. [R and D Alfa Laval Artec Spa Vicenza, Vicenza (Italy)

1999-12-01

An experimental campaign on plate heat exchangers, used as evaporators and condenser in domestic refrigeration loops is presented in this paper. The research's purpose is to test the influence of some thermal-hydraulic parameters on the global overall heat transfer coefficient. R134a, R407C, R410A, and R22 are the fluids tested under reference thermal conditions. The experimental tests allows one to withdraw conclusions on the substitution effect on the thermal and global efficiency of the plant. Also, a new method for calculating the thermodynamical mixture parameters is applied to the condensation of mixtures R407C and R410A and its benefit evaluated. The refrigerant loop overall performance and the condenser global heat transfer coefficient are the parameters chosen to enlighten the characteristics of the alternative refrigerants (R134a, R407C, and R410A) with respect to the fluid that they are supposed to substitute (R22). [Italian] Scambiatori a piastre compatti impiegati come evaporatori e condensatori nei circuiti frigoriferi, sono l'oggetto della ricerca presentata in questo articolo. L'efficienza termica di tali componenti e' valutata in condizioni di riferimento commerciali. I refrigeranti utilizzati sono tre fluidi proposti per sostituire l'R22, un Hcfc, attualmente il refrigerante piu' utilizzato nel condizionamento ambientale. Una serie di prove condotte con quest'ultimo fluido consente di studiare gli effetti della sostituzione del fluido di progetto sulle prestazioni sia degli scambiatori, sia piu' in generale, dell'intero circuito frigorifero. In particolare sono state studiate le prestazioni di due coppie di evaporatori e condensatori in termini di coefficiente globale di scambio termico e di Cop dell'impianto. Nel presente lavoro e' inoltre presentato e utilizzato un metodo termodinamico per il calcolo della temperatura di saturazione per le miscele zeotropiche in bifase; uno dei refrigeranti

On-line purge-and-trap-gas chromatography with flame ionization detection as an alternative analytical method for dimethyl sulphide trace release from marine algae

Energy Technology Data Exchange (ETDEWEB)

Careri, M.; Musci, M.; Bianchi, F.; Mucchino, C. [Parma Univ., Parma (Italy). Dipt. di Chimica Generale ed Inorganica, Chimica Analitica e Chimica Fisica; Azzoni, R.; Viaroli, P. [Parma Univ., Parma (Italy). Dipt. di Scienze Ambientali

2001-10-01

The release of dimethyl sulphide (DMS) by the seaweed Ulva spp at trace level was studied in aqueous solutions at different salinities, temperature and light intensities. For this purpose, the purge-and-trap technique combined with gas chromatography-flame ionization detection was used. The analytical method was evaluated in terms of linearity range, limit of detection, precision and accuracy by considering 10% (w/v) and 30% (w/v) synthetic seawater as aqueous matrices. Calculation of the recovery function evidenced a matrix influence. The method of standard addition was then used for an accurate determination of DMS in synthetic seawater reproduction the matrix effect. DMS fluxes were analysed in batch cultures of Ulva spp reproducing the conditions which usually occur in the Sacca di Goro lagoon (Northern Adriatic Sea, Italy). [Italian] Il rilascio di dimetilsolfuro (DMS) in tracce da parte della macroalga Ulva spp e' stato studiato in soluzioni acquose di differente salinita' mediante la tecnica purge-and-trap accoppiata on-line alla gascromatografia con rivelazione a ionizzazione di fiamma (GC-FID). Il metodo analitico e' stato validato in termini di linearita' di risposta, di limite di rivelabilita', precisione e accuratezza considerando come matrice acqua di mare sintetica a diversa salinita' (10%0 m/v e 30%0 m/v). Il calcolo della funzione di recupero ha consentito di verificare la presenza di errori sistematici dovuti all'effetto matrice. Il metodo sviluppato e' stato quindi applicato a matrici ambientali allo scopo di verificare il rilascio di DMS da parte di Ulva spp, operando in condizioni ambientali simili a quelle che si verificano nella Sacca di Goro (Ferrara, Italia).

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.

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.

Counterbalancing of TH2-driven allergic airway inflammation by IL-12 does not require IL-10.

Science.gov (United States)

Tournoy, K G; Kips, J C; Pauwels, R A

2001-03-01

Asthma is characterized by allergen-induced airway inflammation orchestrated by TH2 cells. The TH1-promoting cytokine IL-12 is capable of inhibiting the TH2-driven allergen-induced airway changes in mice and is therefore regarded as an interesting strategy for treating asthma. The antiallergic effects of IL-12 are only partially dependent of IFN-gamma. Because IL-12 is a potent inducer of the anti-inflammatory cytokine IL-10, the aim of the present study was to investigate in vivo whether the antiallergic effects of IL-12 are mediated through IL-10. C57BL/6J-IL-10 knock-out (IL-10(-/-)) mice were sensitized intraperitoneally to ovalbumin (OVA) and subsequently exposed from day 14 to day 21 to aerosolized OVA (1%). IL-12 was administered intraperitoneally during sensitization, subsequent OVA exposure, or both. IL-12 inhibited the OVA-induced airway eosinophilia, despite the absence of IL-10. Moreover, a shift from a TH2 inflammatory pattern toward a TH1 reaction was observed, with concomitant pronounced mononuclear peribronchial inflammation after IL-12 treatment. Allergen-specific IgE synthesis was completely suppressed only when IL-12 was administered along with the allergen sensitization. Furthermore, treating the animals with IL-12 at the time of the secondary allergen challenge resulted not only in a significant suppression of the airway responsiveness but also in an important IFN-gamma-associated toxicity. These results indicate that IL-12 is able to inhibit allergen-induced airway changes, even in the absence of IL-10. In addition, our results raise concerns regarding the redirection of TH2 inflammation by TH1-inducing therapies because treatment with IL-12 resulted not only in a disappearance of the TH2 inflammation but also in a TH1-driven inflammatory pulmonary pathology.

[Cytokines and malaria. A study of TNF-alpha, IL1-beta, IL6 and IL2R in 28 patients].

Science.gov (United States)

Nicolas, P; Hovette, P; Merouze, F; Touze, J E; Martet, G

1994-01-01

Authors have studied TNF alpha, IL1 bêta, IL6 and RIL2s in 28 malaria illness patients. Increased levels of TNF, IL1 bêta and RIL2s in serum, are observed on admission to hospital. These cytokine levels are decreased, eight days later, after patients are treated. In discussion, TNF levels as a prognosis component is evocated.

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.

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

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...... 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...

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)

Clinical significance of determination of changes of EPS IL-1β, IL-2, IL-10 and LDH5/LDH1 levels in patients with chronic prostatitis

International Nuclear Information System (INIS)

Chen Yongchang

2009-01-01

Objective: To investigate the clinical significance of the changes of expressed prostatic secretion IL-1β, IL-2, IL-10 and LDH5/LDH1 levels in patients with chronic prostatitis. Methods: Expressed prostatic secretion IL-1β, IL-2, IL-10 (with Radioimmunoassay) and LDH5/LDH1 (with cellulose acetate membrane electrophoresis) levels were determined in 32 patients with chronic prostatitis and 35 controls. These 32 patients were of 3 groups: 1)chronic bacterial prostatitis (CBP, n=10) 2) chronic pelvic pain syndrome IIIA (CPPS IIIA n=9) 3) CPPSIIIB n=13. Results: Expressed prostatic secretion levels of IL-1β, IL-2 and LDH5/LDH1 were significantly higher in patients with chronic bacterial prostatitis (CBP) groups than those in controls (all P 0.05). But the expressed prostatic secretion levels of IL-10 were still significantly lower in patients with chronic nonbacterial prostatitis, chronic pelvic pain syndrome(CPPSIIIB) groups than those in controls (all P<0.05). Conclusion: There were changes of expressed prostatic secretion IL-1β, IL-2, IL-10 and LDH5/LDH1 levels in patients with chronic prostatitis. Combined determination of the expressed prostatic secretion 4 markers levels is valuable for the diagnosis of chronic prostatitis and CPPSIII and for differentiation of CPPSIII types. (authors)

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

Elevated levels of circulating IL-18BP and perturbed regulation of IL-18 in schizophrenia

Directory of Open Access Journals (Sweden)

Palladino Ilaria

2012-08-01

Full Text Available Abstract Background The pleiotropic pro-inflammatory cytokine Interleukin (IL-18 has been proposed to play a role in schizophrenia, since elevated circulating levels of its protein and altered frequencies of genetic variants in its molecular system are reported in schizophrenic patients. Methods We analyzed 77 patients with schizophrenia diagnosis (SCZ and 77 healthy control subjects (HC for serum concentration of both IL-18 and its natural inhibitor, the IL-18 binding protein (IL-18BP. Results We confirmed that serum levels of total IL-18 are significantly increased in SCZ, as compared to HC. However, due to a highly significant increase in levels of circulating IL-18BP in SCZ, as compared to HC, the levels of free, bioactive IL-18 are not significantly different between the two groups. In addition, the relationships between the levels of IL-18 and its inhibitor, as well as between the two molecules and age appear dissimilar for SCZ and HC. In particular, the elevated levels of IL-18BP, likely a consequence of the body’s attempt to counteract the early prominent inflammation which characterizes schizophrenia, are maintained in earlier and later stages of the disease. However, the IL-18BP elevation appears ineffective to balance the IL-18 system in younger SCZ patients, while in older patients the levels of circulating bioactive IL-18 are comparable to those of HC, if not lower. Conclusions In conclusion, these findings indicate that the IL-18 system is perturbed in schizophrenia, supporting the idea that this pro-inflammatory cytokine might be part of a pathway of genetic and environmental components for vulnerability to the disease.

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.

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.

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

A comparison of blood and cerebrospinal fluid cytokines (IL-1β, IL-6, IL-18, TNF-α in neonates with perinatal hypoxia

Directory of Open Access Journals (Sweden)

Darinka Šumanović-Glamuzina

2017-08-01

Full Text Available Perinatal hypoxia-ischemia is a specific and important pathological event in neonatal care practice. The data on relationship between the concentrations of cytokines in blood and cerebrospinal fluid (CSF and perinatal brain injury are scarce. The aim of this study is to evaluate changes in interleukin (IL-1β, IL-6, and IL-18 and tumor necrosis factor alpha (TNF-α levels in newborns with perinatal hypoxia (PNH. CSF and serum samples of 35 term and near-term (35-40 weeks newborns with PNH, at the age of 3-96 hours, were analyzed using enzyme-linked immunosorbent assay. Control group consisted of 25 non-asphyxic/non-hypoxic infants of the same age sampled for clinically suspected perinatal meningitis, but proven negative and healthy otherwise. The cytokine values in CSF and serum samples were determined in relation to initial hypoxic-ischemic encephalopathy (HIE staged according the Sarnat/Sarnat method, and compared with neurological outcome at 12 months of age estimated using Amiel-Tison procedure. The concentrations of IL-6 and TNF-α in serum of PNH patients were significantly higher compared to control group (p = 0.0407 and p = 0.023, respectively. No significant difference between average values of cytokines in relation to the stage of HIE was observed. Significantly higher levels of IL-6 and IL-18 corresponded to a mildly abnormal neurological outcome, while higher levels of IL-6 and TNF-α corresponded to a severely abnormal neurological outcome, at 12 months of age. Elevated serum levels of IL-6 and TNF-α better corresponded with hypoxia/ischemia compared to CSF values, within 96 hours of birth. Also, higher serum levels of IL-6, TNF-α, and IL-18 corresponded better with abnormal neurological outcome at 12 months of age, compared to CSF values.

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.

The situation of the wolf (Canis lupus in the area of the Regional Park of the Simbruini Mountains / La situazione del Lupo (Canis lupus nell'area del Parco Naturale Regionale dei Monti Simbruini

Directory of Open Access Journals (Sweden)

Paolo Verucci

1992-07-01

Full Text Available Abstract This work presents the results of a field research on the species Canis lupus in the Regional Park of the Simbruini Mountains. In relation to Wolf conservation, an investigation on feral and free-roving dogs was carried out. The method of snowtracking was used for Wolves and Feral dogs, the method of sighting was used for free-roving dogs. The research underlines the importance of the Simbruini Mountains for the protection of Wolf in central Apennines and the factors, at present, threatening its survival. Riassunto Nel presente lavoro vengono illustrati i risultati di una ricerca sul campo sulla specie Canis lupus nel Parco Naturale Regionale dei Monti Simbruini. In relazione agli aspetti riguardanti la conservazione del Lupo, è stata compiuta un'indagine sul fenomeno del randagismo canino. Per i lupi e i cani inselvatichiti è stato usato il metodo dello snowtracking, per le altre categorie di Cani è stato utilizzato il metodo dell'avvistamento. La ricerca ha messo in luce l'importanza dell'area dei Simbruini per la salvaguardia del Lupo nell'Appennino centrale e i fattori che, attualmente, ne minacciano la sopravvivenza.

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.

Il corpo narratore

Directory of Open Access Journals (Sweden)

Ivano Gamelli

2005-09-01

Full Text Available Sapere cosa provo attraverso il mio corpo di fronte all’altro mi permette non solo di capire cosa l'altro prova, soprattutto di generare naturalmente un’effettiva sintonizzazione, di evidenziare e nominare emozioni e sentimenti che in-formano la relazione con quel particolare bambino, adolescente o adulto che sia. Il rapporto con il linguaggio del corpo, prima ancora di divenire pratica psicopedagogica, è una 'pedagogia dell'esistenza'. Una pratica della nostra quotidianità che possiamo affinare oltre e prima che essa diventi pratica psicopedagogica.

Targeting the IL-17/IL-6 axis can alter growth of Chronic Lymphocytic Leukemia in vivo/in vitro.

Science.gov (United States)

Zhu, Fang; McCaw, Lindsay; Spaner, David E; Gorczynski, Reginald M

2018-03-01

The tumor microenvironment (TME) is critical to the longevity of tumor B cells in chronic lymphocytic leukemia (CLL). Bone marrow mesenchymal stem cells (BMMSCs) and the cytokines they produce including IL-6 are important components of the TME in CLL. We found BMMSCs supported the survival of CLL cells in vitro through an IL-6 dependent mechanism. IL-17 which induces IL-6 generation in a variety of cells increased production of IL-6 both in CLL cells and BMMSCs in vitro. In a xenograft CLL mouse model, BMMSCs and the culture supernatant of BMMSCs increased engraftment of CLL cells through an IL-6 mediated mechanism with human recombinant IL-6 showing similar effects in vivo. Human recombinant IL-17 treatment also increased CLL engraftment in mice through an IL-6 mediated mechanism. Plasma of CLL patients showed elevated levels of both IL-6 and IL-17 by ELISA compared with healthy controls, with levels of IL-6 linearly correlated with IL-17 levels. CLL patients requiring fludarabine based chemotherapy expressed higher levels of IL-6 and IL-17, while CLL patients with the lowest levels of IgA/IgM had higher levels of IL-6, but not IL-17. These data imply an important role for the IL-17/IL-6 axis in CLL which could be therapeutic targets. Copyright © 2018 Elsevier Ltd. All rights reserved.

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...

IL-15/IL-15 receptor biology: a guided tour through an expanding universe.

Science.gov (United States)

Budagian, Vadim; Bulanova, Elena; Paus, Ralf; Bulfone-Paus, Silvia

2006-08-01

The cytokine interleukin-15 (IL-15) has a key role in promoting survival, proliferation and activation of natural killer (NK) and CD8+ T cells. Despite its functional similarities to IL-2, IL-15 affects a wider range of target cell populations and utilizes different mechanisms of signaling. Here, we review recent advances in the IL-15-mediated signaling, and in the functional properties on cells besides T lymphocytes and NK cells. These are discussed in the context of their potential clinical and therapeutic relevance.

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.

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. PMID:25849644

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.

Predictive value of IL-35 and IL-17 in diagnosis of childhood asthma.

Science.gov (United States)

Mansour, Amira Ibrahim; Abd Almonaem, Eman Rateb; Behairy, Ola Galal; Gouda, Tahany Mahmoud

2017-09-01

This study aimed to evaluate the correlation between serum levels of IL-17 and IL-35 and the presence and severity of childhood asthma. The study was performed on 60 diagnosed asthmatic children, who were further classified into four groups according to the Global Initiative for Asthma Guidelines for Asthma Severity and Control (GINA) 2016, plus 30 age- and sex-matched apparently healthy children. All participants were subjected to full medical history, clinical examination, pulmonary function tests and laboratory evaluation in the form of complete blood count (CBC), serum total IgE, IL-17 and IL-35 by ELISA. Our results revealed that eosinophils count, IgE and IL-17 were significantly higher in the asthmatic group than the control group (p 13.1 pg/mL; this value could predict childhood asthma with sensitivity of 81.7% and 83.3%, and specificity of 76.7% and 70%, respectively. A combination of both cytokines yielded an increase in sensitivity to 95%. In conclusion, in the current study, IL-17 is upregulated while IL-35 is downregulated in childhood asthma with a significant negative correlation between both. These results suggest that both may play an important role in the pathogenesis of childhood asthma.

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...

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

Genetic regulation of IL1RL1 methylation 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.

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-09-05

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

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

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.

Targeting the IL-33/IL-13 Axis for Respiratory Viral Infections.

Science.gov (United States)

Donovan, Chantal; Bourke, Jane E; Vlahos, Ross

2016-04-01

Lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are highly prevalent worldwide. One of the major factors that limits the efficacy of current medication in these patients are viral infections, leading to exacerbations of symptoms and decreased quality of life. Current pharmacological strategies targeting virus-induced lung disease are problematic due to antiviral resistance and the requirement for strain-specific vaccination. Thus, new therapeutic strategies are urgently required. In this Opinion article, we provide state-of-the-art evidence from humans and preclinical animal models implicating the interleukin (IL)-33/IL-13 axis in virus-induced lung disease. Thus, targeting the IL-33/IL-13 axis may be a feasible way to overcome the limitations of current therapy used to treat virus-induced exacerbations of lung disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

International Nuclear Information System (INIS)

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

2016-01-01

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

IL-4 and IL-13 Compromise the Sinonasal Epithelial Barrier and Perturb Intercellular Junction Protein Expression

Science.gov (United States)

Wise, Sarah K.; Laury, Adrienne M.; Katz, Elizabeth H.; Den Beste, Kyle A.; Parkos, Charles A.; Nusrat, Asma

2014-01-01

Introduction Altered expression of epithelial intercellular junction proteins has been observed in sinonasal biopsies from nasal polyps and epithelial layers cultured from nasal polyp patients. These alterations comprise a “leaky” epithelial barrier phenotype. We hypothesize that Th2 cytokines IL-4 and IL-13 modulate epithelial junction proteins thereby contributing to the leaky epithelial barrier. Methods Differentiated primary sinonasal epithelial layers cultured at the air-liquid interface were exposed to IL-4, IL-13, and controls for 24 hours at 37°C. Epithelial resistance measurements were taken every 4 hours during cytokine exposure. Western blot and immunofluorescence staining/confocal microscopy were used to assess changes in a panel of tight and adherens junction proteins. Western blot densitometry was quantified with image analysis. Results IL-4 and IL-13 exposure resulted in a mean decrease in transepithelial resistance at 24 hours to 51.6% (n=6) and 68.6% (n=8) of baseline, respectively. Tight junction protein JAM-A expression decreased 42.2% with IL-4 exposure (n=9) and 37.5% with IL-13 exposure (n=9). Adherens junction protein E-cadherin expression decreased 35.3% with IL-4 exposure (n=9) and 32.9% with IL-13 exposure (n=9). Tight junction protein claudin-2 showed more variability but had a trend toward higher expression with Th2 cytokine exposure. There were no appreciable changes in claudin-1, occludin, or ZO-1 with IL-4 or IL-13 exposure. Conclusion Sinonasal epithelial exposure to Th2 cytokines IL-4 and IL-13 results in alterations in intercellular junction proteins, reflecting increased epithelial permeability. Such changes may explain some of the phenotypic manifestations of Th2-mediated sinonasal disease, such as edema, nasal discharge, and environmental reactivity. PMID:24510479

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.

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

Directory of Open Access Journals (Sweden)

Heather R Conti

Full Text Available 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.

IL-17 Induction by ArtinM is Due to Stimulation of IL-23 and IL-1 Release and/or Interaction with CD3 in CD4+ T Cells.

Science.gov (United States)

da Silva, Thiago Aparecido; Mariano, Vania Sammartino; Sardinha-Silva, Aline; de Souza, Maria Aparecida; Mineo, Tiago Wilson Patriarca; Roque-Barreira, Maria Cristina

2016-01-01

ArtinM is a D-mannose-binding lectin extracted from the seeds of Artocarpus heterophyllus that interacts with TLR2 N-glycans and activates antigen-presenting cells (APCs), as manifested by IL-12 production. In vivo ArtinM administration induces Th1 immunity and confers protection against infection with several intracellular pathogens. In the murine model of Candida albicans infection, it was verified that, in addition to Th1, ArtinM induces Th17 immunity manifested by high IL-17 levels in the treated animals. Herein, we investigated the mechanisms accounting for the ArtinM-induced IL-17 production. We found that ArtinM stimulates the IL-17 production by spleen cells in BALB/c or C57BL/6 mice, a response that was significantly reduced in the absence of IL-23, MyD88, or IL-1R. Furthermore, we showed that ArtinM directly induced the IL-23 mRNA expression and the IL-1 production by macrophages. Consistently, in cell suspensions depleted of macrophages, the IL-17 production stimulated by ArtinM was reduced by 53% and the exogenous IL-23 acted synergistically with ArtinM in promoting IL-17 production by spleen cell suspensions. We verified that the absence of IL-23, IL-1R, or MyD88 inhibited, but did not block, the IL-17 production by ArtinM-stimulated spleen cells. Therefore, we investigated whether ArtinM exerts a direct effect on CD4+ T cells in promoting IL-17 production. Indeed, spleen cell suspensions depleted of CD4+ T cells responded to ArtinM with very low levels of IL-17 release. Likewise, isolated CD4+ T cells under ArtinM stimulus augmented the expression of TGF-β mRNA and released high levels of IL-17. Considering the observed synergism between IL-23 and ArtinM, we used cells from IL-23 KO mice to assess the direct effect of lectin on CD4+ T cells. We verified that ArtinM increased the IL-17 production significantly, a response that was inhibited when the CD4+ T cells were pre-incubated with anti-CD3 antibody. In conclusion, ArtinM stimulates the production

IL-17 Induction by ArtinM is Due to Stimulation of IL-23 and IL-1 Release and/or Interaction with CD3 in CD4+ T Cells.

Directory of Open Access Journals (Sweden)

Thiago Aparecido da Silva

Full Text Available ArtinM is a D-mannose-binding lectin extracted from the seeds of Artocarpus heterophyllus that interacts with TLR2 N-glycans and activates antigen-presenting cells (APCs, as manifested by IL-12 production. In vivo ArtinM administration induces Th1 immunity and confers protection against infection with several intracellular pathogens. In the murine model of Candida albicans infection, it was verified that, in addition to Th1, ArtinM induces Th17 immunity manifested by high IL-17 levels in the treated animals. Herein, we investigated the mechanisms accounting for the ArtinM-induced IL-17 production. We found that ArtinM stimulates the IL-17 production by spleen cells in BALB/c or C57BL/6 mice, a response that was significantly reduced in the absence of IL-23, MyD88, or IL-1R. Furthermore, we showed that ArtinM directly induced the IL-23 mRNA expression and the IL-1 production by macrophages. Consistently, in cell suspensions depleted of macrophages, the IL-17 production stimulated by ArtinM was reduced by 53% and the exogenous IL-23 acted synergistically with ArtinM in promoting IL-17 production by spleen cell suspensions. We verified that the absence of IL-23, IL-1R, or MyD88 inhibited, but did not block, the IL-17 production by ArtinM-stimulated spleen cells. Therefore, we investigated whether ArtinM exerts a direct effect on CD4+ T cells in promoting IL-17 production. Indeed, spleen cell suspensions depleted of CD4+ T cells responded to ArtinM with very low levels of IL-17 release. Likewise, isolated CD4+ T cells under ArtinM stimulus augmented the expression of TGF-β mRNA and released high levels of IL-17. Considering the observed synergism between IL-23 and ArtinM, we used cells from IL-23 KO mice to assess the direct effect of lectin on CD4+ T cells. We verified that ArtinM increased the IL-17 production significantly, a response that was inhibited when the CD4+ T cells were pre-incubated with anti-CD3 antibody. In conclusion, Artin

Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer.

Science.gov (United States)

Bharti, Rashmi; Dey, Goutam; Das, Anjan Kumar; Mandal, Mahitosh

2018-04-26

Monoamine oxidases (MAO) are mitochondrial enzymes functioning in oxidative metabolism of monoamines. The action of MAO-A has been typically described in neuro-pharmacological domains. Here, we have established a co-relation between IL-6/IL-6R and MAO-A and their regulation in hypoxia induced invasion/angiogenesis. We employed various in-vitro and in-vivo techniques and clinical samples. We studied a co-relation among MAO-A and IL-6/IL-6R and tumour angiogenesis/invasion in hypoxic environment in breast cancer model. Activation of IL-6/IL-6R and its downstream was found in hypoxic cancer cells. This elevation of IL-6/IL-6R caused sustained inhibition of MAO-A in hypoxic environment. Inhibition of IL-6R signalling or IL-6R siRNA increased MAO-A activity and inhibited tumour angiogenesis and invasion significantly in different models. Further, elevation of MAO-A with 5-azacytidine (5-Aza) modulated IL-6 mediated angiogenesis and invasive signatures including VEGF, MMPs and EMT in hypoxic breast cancer. High grade invasive ductal carcinoma (IDC) clinical specimen displayed elevated level of IL-6R and depleted MAO-A expression. Expression of VEGF and HIF-1α was unregulated and loss of E-Cadherin was observed in high grade IDC tissue specimen. Suppression of MAO-A by IL-6/IL-6R activation promotes tumour angiogenesis and invasion in hypoxic breast cancer environment.

The distribution of IL-13 receptor alpha1 expression on B cells, T cells and monocytes and its regulation by IL-13 and IL-4.

Science.gov (United States)

Graber, P; Gretener, D; Herren, S; Aubry, J P; Elson, G; Poudrier, J; Lecoanet-Henchoz, S; Alouani, S; Losberger, C; Bonnefoy, J Y; Kosco-Vilbois, M H; Gauchat, J F

1998-12-01

To study the expression of IL-13 receptor alpha1 (IL-13Ralpha1), specific monoclonal antibodies (mAb) were generated. Surface expression of the IL-13Ralpha1 on B cells, monocytes and T cells was assessed by flow cytometry using these specific mAb. Among tonsillar B cells, the expression was the highest on the IgD+ CD38- B cell subpopulation which is believed to represent naive B cells. Expression was also detectable on a large fraction of the IgD-CD38- B cells but not on CD38+ B cells. Activation under conditions which promote B cell Ig class switching up-regulated the expression of the receptor. However, the same stimuli had an opposite effect for IL-13Ralpha1 expression levels on monocytes. While IL-13Ralpha1 mRNA was clearly detectable in T cell preparations, no surface expression was detected. However, permeabilization of the T cells showed a clear intracellular expression of the receptor. A soluble form of the receptor was immunoprecipitated from the supernatant of activated peripheral T cells, suggesting that T cell IL-13Ralpha1 might have functions unrelated to the capacity to form a type II IL-4/IL-13R with IL-4Ralpha.

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...... in the first 24 h after trauma and to assess the relationship with severity of injury and mortality. METHODS: Prospective, descriptive cohort study in a Level 1 trauma centre, Copenhagen, Denmark. We included 265 consecutive adult trauma patients admitted directly from the accident scene during an 18-month...... 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...

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.

In vitro progesterone modulation on bacterial endotoxin-induced production of IL-1β, TNFα, IL-6, IL-8, IL-10, MIP-1α, and MMP-9 in pre-labor human term placenta.

Science.gov (United States)

Garcia-Ruíz, G; Flores-Espinosa, P; Preciado-Martínez, E; Bermejo-Martínez, L; Espejel-Nuñez, A; Estrada-Gutierrez, G; Maida-Claros, R; Flores-Pliego, A; Zaga-Clavellina, Veronica

2015-10-07

During human pregnancy, infection/inflammation represents an important factor that increases the risk of developing preterm labor. The purpose of this study was to determine if pre-treatment with progesterone has an immunomodulatory effect on human placenta production of endotoxin-induced inflammation and degradation of extracellular matrix markers. Placentas were obtained under sterile conditions from pregnancies delivered at term before the onset of labor by cesarean section. Explants from central cotyledons of 10 human placentas were pre-treated with different concentrations of progesterone (0.01, 01, 1.0 μM) and then stimulated with 1000 ng/mL of LPS of Escherichia coli. Cytokines TNFα, IL-1β, IL-6, IL-8, MIP-1α, IL-10 concentrations in the culture medium were then measured by specific ELISA. Secretion profile of MMP-9 was evaluated by ELISA and zymogram. Statistical differences were determined by one-way ANOVA followed by the appropriate ad hoc test; P progesterone significantly blunted (73, 56, 56, 75, 25, 48 %) the secretion of TNF-α, IL-1β, IL-6, IL-8, MIP-1α, IL-10, respectively. The MMP-9 induced by LPS treatment was inhibited only with the highest concentration of progesterone. Mifepristone (RU486) blocked the immunosuppressive effect of progesterone. The present results support the concept that progesterone could be part of the compensatory mechanism that limits the inflammation-induced cytotoxic effects associated with an infection process during gestation.

IL-13 and the IL-13 receptor as therapeutic targets for asthma and allergic disease.

Science.gov (United States)

Mitchell, Jesse; Dimov, Vesselin; Townley, Robert G

2010-05-01

It is widely accepted that T-helper 2 cell (Th2) cytokines play an important role in the maintenance of asthma and allergy. Emerging evidence has highlighted the role of IL-13 in the pathogenesis of these diseases. In particular, IL-13 is involved in the regulation of IgE synthesis, mucus hypersecretion, subepithelial fibrosis and eosinophil infiltration, and has been associated with the regulation of certain chemokine receptors, notably CCR5. Thus, targeting IL-13 and its associated receptors may be a therapeutic approach to the treatment of asthma and/or allergy. Pharmaceutical and biotechnology companies are researching various strategies, based on this approach, aimed at binding IL-13, increasing the level of the IL-13 decoy receptor, IL-13Ralpha2, or blocking the effect of the chemokine receptor CCR5. This review focuses on the therapeutic potential of anti-IL-13 agents and their role in the treatment of asthma and allergy.

IL26 gene inactivation in Equidae.

Science.gov (United States)

Shakhsi-Niaei, M; Drögemüller, M; Jagannathan, V; Gerber, V; Leeb, T

2013-12-01

Interleukin-26 (IL26) is a member of the IL10 cytokine family. The IL26 gene is located between two other well-known cytokines genes of this family encoding interferon-gamma (IFNG) and IL22 in an evolutionary conserved gene cluster. In contrast to humans and most other mammals, mice lack a functional Il26 gene. We analyzed the genome sequences of other vertebrates for the presence or absence of functional IL26 orthologs and found that the IL26 gene has also become inactivated in several equid species. We detected a one-base pair frameshift deletion in exon 2 of the IL26 gene in the domestic horse (Equus caballus), Przewalski horse (Equus przewalskii) and donkey (Equus asinus). The remnant IL26 gene in the horse is still transcribed and gives rise to at least five alternative transcripts. None of these transcripts share a conserved open reading frame with the human IL26 gene. A comparative analysis across diverse vertebrates revealed that the IL26 gene has also independently been inactivated in a few other mammals, including the African elephant and the European hedgehog. The IL26 gene thus appears to be highly variable, and the conserved open reading frame has been lost several times during mammalian evolution. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation for Animal Genetics.

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

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.

Increased Circulating Th17 Cells, Serum IL-17A, and IL-23 in Takayasu Arteritis.

Science.gov (United States)

Misra, Durga Prasanna; Chaurasia, Smriti; Misra, Ramnath

2016-01-01

Introduction. Th17, γδT, NK, and NKT cells in peripheral blood and serum IL-17 and IL-23 in Takayasu arteritis (TA) were measured and correlated with disease activity. Methods. Th17 (anti-CD3APC, CD4PECy7, and IL-17PE), NKT, NK (anti-CD3APC, CD56FITC), and γδT (anti-CD3FITC and γδTCRAPC) cells were enumerated by flow cytometry in peripheral blood of 30 patients with TA (ACR1990 criteria) and 20 healthy controls, serum IL-17 and IL-23 measured by ELISA. Relation with disease activity (NIH criteria, ITAS2010) was analyzed (using nonparametric tests, median with interquartile range). Results. Mean age of patients was 33.47 ± 11.78 years (25 females); mean symptom duration was 7.1 ± 5.3 years. 13 were not on immunosuppressants; 12 were active (ITAS2010 ≥ 4). The percentage of Th17 cells was significantly expanded in TA (patients 2.1 (1.5-3.2) versus controls 0.75 (0.32-1.2); p < 0.0001) with no differences in other cell populations. Serum IL-17 and IL-23 (pg/mL) in patients (6.2 (4.6-8.5) and 15 (14.9-26.5), resp.) were significantly higher (p < 0.001) than controls (3.9 (3.9-7.3) and undetectable median value, resp.). Subgroup analysis revealed no correlation of Th17 cells, serum IL-17, and IL-23 with disease activity or medications, nor any significant difference before and after medication. Conclusions. There is significant expansion of Th17 cells and elevated serum IL-17 and IL-23 levels in TA patients compared to healthy controls.

Macrophages as IL-25/IL-33-responsive cells play an important role in the induction of type 2 immunity.

Directory of Open Access Journals (Sweden)

Zhonghan Yang

Full Text Available Type 2 immunity is essential for host protection against nematode infection but is detrimental in allergic inflammation or asthma. There is a major research focus on the effector molecules and specific cell types involved in the initiation of type 2 immunity. Recent work has implicated an important role of epithelial-derived cytokines, IL-25 and IL-33, acting on innate immune cells that are believed to be the initial sources of type 2 cytokines IL-4/IL-5/IL-13. The identities of the cell types that mediate the effects of IL-25/IL-33, however, remain to be fully elucidated. In the present study, we demonstrate that macrophages as IL-25/IL-33-responsive cells play an important role in inducing type 2 immunity using both in vitro and in vivo approaches. Macrophages produced type 2 cytokines IL-5 and IL-13 in response to the stimulation of IL-25/IL-33 in vitro, or were the IL-13-producing cells in mice administrated with exogenous IL-33 or infected with Heligmosomoides bakeri. In addition, IL-33 induced alternative activation of macrophages primarily through autocrine IL-13 activating the IL-4Rα-STAT6 pathway. Moreover, depletion of macrophages attenuated the IL-25/IL-33-induced type 2 immunity in mice, while adoptive transfer of IL-33-activated macrophages into mice with a chronic Heligmosomoides bakeri infection induced worm expulsion accompanied by a potent type 2 protective immune response. Thus, macrophages represent a unique population of the innate immune cells pivotal to type 2 immunity and a potential therapeutic target in controlling type 2 immunity-mediated inflammatory pathologies.

Association between genes encoding components of the IL-4/IL-4 receptor pathway and dermatitis in children.

Science.gov (United States)

Hussein, Yousri M; Shalaby, Sally M; Nassar, Amani; Alzahrani, Saad S; Alharbi, Ayman S; Nouh, Maha

2014-07-25

To determine whether IL-4, IL-4Rα and STAT6 polymorphisms are associated with susceptibility to dermatitis in Egyptian children. We genotyped three groups of children, consisting of 106 atopic dermatitis (AD) children, 95 non-AD children, and 100 of healthy controls, for IL-4 (-590 C/T), (-33 C/T), IL-4Rα (I50V), (Q576R) and STAT6 (2964 G/A), (2892 C/T) gene polymorphisms using PCR-RFLP assay. Total serum IgE and serum IL-4 levels were detected by ELISA. There was a non-significant association of IL-4 -590 C/T, -33 C/T polymorphisms in the children with non-AD or those with AD when compared with the controls. We identified a significant association between IL-4Rα I50V, Q576R polymorphisms and dermatitis susceptibility in AD (p=0.002, dermatitis was found. Patients who were carriers of IL4 -590C, IL-4Rα I50V G, STAT6 2964 A and STAT6 2892 T had an increased risk of AD [OR and 95% CI: 3.2 (2.5-4.2), p=0.005]. Furthermore, there was no relation between each polymorphism and serum IL-4 level (p>0.05 for each) while homozygosity for the risk alleles of IL-4, IL-4Rα and STAT6 SNPs were significantly associated with increased total IgE levels in all subjects. In Egyptian children, the IL-4Rα and the STAT6 polymorphism may play a role in susceptibility to AD. In addition, gene-gene interaction between the IL-4, the IL-4Rα and the STAT6 significantly increases an individual's susceptibility to AD. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Pfeilschifter Josef

2008-09-01

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

Evaluating ESWL-induced renal injury based on urinary TNF-α, IL-1α, and IL-6 levels.

Science.gov (United States)

Goktas, Cemal; Coskun, Abdurrahman; Bicik, Zerrin; Horuz, Rahim; Unsal, Ibrahim; Serteser, Mustafa; Albayrak, Selami; Sarıca, Kemal

2012-10-01

Extracorporeal shockwave lithotripsy (ESWL) has dramatically changed the treatment of urinary lithiasis and has been the first treatment option for the majority of patients for more than two decades. Despite its significant benefits, it induces acute renal injury that extends from the papilla to the outer cortex. We evaluated the severity of the inflammatory response to ESWL by measuring the urinary excretion of the cytokines TNF-α, IL-1α, and IL-6. The study included 21 selected patients and 14 control subjects. All patients underwent the same ESWL procedure (2,500 shockwaves at 100 shockwaves/min and 0.039 J from the lithotripter). Urine TNF-α, IL-1α, and IL-6 levels were measured using standard ELISA kits. In the study population (patients and controls), we did not detect TNF-α in the urine samples. The levels of both IL-1α (2.5 pg/ml) and IL-6 (3.8 pg/ml) measured before ESWL were not significantly different from the control group (2.5 and 5.2 pg/ml, respectively; p > 0.05). Twenty-four hours after ESWL, in contrast to IL-1α (4 pg/ml), urine IL-6 (19.7 pg/ml) increased significantly (p ESWL, IL-1α increased to 5 pg/ml, while IL-6 (7 pg/ml) decreased to the control level. Urine cytokine levels may be used to evaluate the inflammatory response to ESWL. After ESWL, IL-6 levels increased in the early phase, while IL-1α levels increased later. These two markers may be used to measure the severity of inflammation. In contrast to IL-1α and IL-6, urine TNF-α excretion was not increased by ESWL. We believe that the inflammatory response to ESWL can be detected by the urinary excretion of IL-1α for up to 14 days.

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.

A preliminary study on the association of single nucleotide polymorphisms of interleukin 4 (IL4, IL13, IL4 receptor alpha (IL4Rα & Toll-like receptor 4 (TLR4 genes with asthma in Indian adults

Directory of Open Access Journals (Sweden)

Parisa Davoodi

2015-01-01

Full Text Available Background & objectives: Interleukin 4 (IL4 and IL13 genes are believed to be responsible for inflammation of the airways in asthmatics. These share a common receptor component called IL4Rα which is another potentially important candidate gene linked to asthma phenotypes. Another gene Toll-like receptor 4 (TLR4 might affect the incidence or progression of asthma through the expression of proinflammatory genes. Several single nucleotide polymorphisms (SNPs in IL4, IL13, IL4Rα and TLR4 have been reported to be linked to asthma or related phenotypes in several ethnic populations using linkage studies and association studies. However, the results have not been consistent. We investigated five SNPs (C-589T and C-33T of IL4, G+2044A of IL13, A+1902G of IL4Rα, and A+896G of TLR4 in patients with adult onset asthma to evaluate their role in manifestation and severity of asthma. Methods: Adult (>18 yr of age patients with asthma (n=100 and healthy controls (n=50 were included in the study. Genotyping was performed using sequenom MassARRAY technology. Results: The mutant alleles of the C-589T and C-33T SNPs in the promoter region of IL4 were present in 4 per cent patients with asthma but absent from the control group suggesting that the variations in IL4 may contribute to asthma occurrence. The SNPs of other genes were seen in both controls and patients. Interpretation & conclusions: The results suggest the possible association between the genetic distribution of C-589T and C-33T SNPs of IL4 with asthma in Indian adults.

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

Directory of Open Access Journals (Sweden)

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.

IL-17 for therapy.

Science.gov (United States)

Kurschus, Florian C; Moos, Sonja

2017-09-01

The cytokine IL-17 is now a target for an array of therapeutic monoclonal antibodies supposed to treat a variety of inflammatory diseases. The forerunner Secukinumab, an IL-17A neutralizing antibody, is meanwhile approved as first-line treatments for moderate-to-severe plaque psoriasis, and as second-line treatment for psoriatic arthritis and ankylosing spondylitis. Ixekizumab and Brodalumab, both also targeting the IL-17 pathway, were also recently approved by the FDA for plaque psoriasis. Using mice overexpressing IL-17A in a tissue of choice, we showed that the ectopic expression of this cytokine in keratinocytes resulted in a spontaneous and very strong form of psoriasis-like dermatitis. Interestingly, this model showed some typical comorbidities found in humans with psoriasis. In this review, we will discuss why IL-17 is a good target especially in psoriasis and what we learned from mouse models about its functions in pathological situations. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Endogenous IL-1 in Cognitive Function and Anxiety: A Study in IL-1RI−/− Mice

Science.gov (United States)

Murray, Carol L.; Obiang, Pauline; Bannerman, David; Cunningham, Colm

2013-01-01

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

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

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.

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.

Construction of an expression system for bioactive IL-18 and generation of recombinant canine distemper virus expressing IL-18.

Science.gov (United States)

Liu, Yuxiu; Sato, Hiroki; Hamana, Masahiro; Moonan, Navita Anisia; Yoneda, Misako; Xia, Xianzhu; Kai, Chieko

2014-09-01

Interleukin 18 (IL-18) plays an important role in the T-helper-cell type 1 immune response against intracellular parasites, bacteria and viral infections. It has been widely used as an adjuvant for vaccines and as an anticancer agent. However, IL-18 protein lacks a typical signal sequence and requires cleavage into its mature active form by caspase 1. In this study, we constructed mammalian expression vectors carrying cDNA encoding mature canine IL-18 (cIL-18) or mouse IL-18 (mIL-18) fused to the human IL-2 (hIL-2) signal sequence. The expressed proIL-18 proteins were processed to their mature forms in the cells. The supernatants of cells transfected with these plasmids induced high interferon-γ production in canine peripheral blood mononuclear cells or mouse splenocytes, respectively, indicating the secretion of bioactive IL-18. Using reverse genetics, we also generated a recombinant canine distemper virus that expresses cIL-18 or mIL-18 fused to the hIL-2 signal sequence. As expected, both recombinant viruses produced mature IL-18 in the infected cells, which secreted bioactive IL-18. These results indicate that the signal sequence from hIL-2 is suitable for the secretion of mature IL-18. These recombinant viruses can also potentially be used as immunoadjuvants and agents for anticancer therapies in vivo.

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.

Plasma cytokine profile in tropical endomyocardial fibrosis: predominance of TNF-a, IL-4 and IL-10.

Directory of Open Access Journals (Sweden)

Aline S Bossa

Full Text Available BACKGROUND: The participation of immune/inflammatory mechanisms in the pathogenesis of tropical endomyocardial fibrosis (EMF has been suggested by the finding of early blood and myocardial eosinophilia. However, the inflammatory activation status of late-stage EMF patients is still unknown. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated pro- and anti-inflammatory cytokine levels in plasma samples from late stage EMF patients. Cytokine levels of Tumor Necrosis Factor (TNF-α, Interferon (IFN-γ, Interleukin (IL-2, IL-4, IL-6, and IL-10 were assayed in plasma samples from 27 EMF patients and compared with those of healthy control subjects. All EMF patients displayed detectable plasma levels of at least one of the cytokines tested. We found that TNF-α, IL-6, IL-4, and IL-10 were each detected in at least 74% of tested sera, and plasma levels of IL-10, IL-4, and TNF-α were significantly higher than those of controls. Plasma levels of such cytokines positively correlated with each other. CONCLUSIONS/SIGNIFICANCE: The mixed pro- and anti-inflammatory/Th2circulating cytokine profile in EMF is consistent with the presence of a persistent inflammatory stimulus. On the other hand, the detection of increased levels of TNF-α may be secondary to the cardiovascular involvement observed in these patients, whereas IL-4 and IL-10 may have been upregulated as a homeostatic mechanism to buffer both production and deleterious cardiovascular effects of pro-inflammatory cytokines. Further studies might establish whether these findings play a role in disease pathogenesis.

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/.

IL-1 receptor-antagonist (IL-1Ra) knockout mice show anxiety-like behavior by aging.

Science.gov (United States)

Wakabayashi, Chisato; Numakawa, Tadahiro; Odaka, Haruki; Ooshima, Yoshiko; Kiyama, Yuji; Manabe, Toshiya; Kunugi, Hiroshi; Iwakura, Yoichiro

2015-07-10

Interleukin 1 (IL-1) plays a critical role in stress responses, and its mRNA is induced in the brain by restraint stress. Previously, we reported that IL-1 receptor antagonist (IL-1Ra) knockout (KO) mice, which lacked IL-1Ra molecules that antagonize the IL-1 receptor, showed anti-depression-like behavior via adrenergic modulation at the age of 8 weeks. Here, we report that IL-1Ra KO mice display an anxiety-like phenotype that is induced spontaneously by aging in the elevated plus-maze (EPM) test. This anxiety-like phenotype was improved by the administration of diazepam. The expression of the anxiety-related molecule glucocorticoid receptor (GR) was significantly reduced in 20-week-old but not in 11-week-old IL-1Ra KO mice compared to wild-type (WT) littermates. The expression of the mineralocorticoid receptor (MR) was not altered between IL-1Ra KO mice and WT littermates at either 11 or 20 weeks old. Analysis of monoamine concentration in the hippocampus revealed that tryptophan, the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), and the dopamine metabolite homovanillic acid (HVA) were significantly increased in 20-week-old IL-1Ra KO mice compared to littermate WT mice. These findings strongly suggest that the anxiety-like behavior observed in older mice was caused by the complicated alteration of monoamine metabolism and/or GR expression in the hippocampus. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

Viva il GIS Day!

Directory of Open Access Journals (Sweden)

Redazione Redazione

2007-03-01

Full Text Available Il GIS Day è sponsorizzato oltre che da ESRI, dalla National Geographic Society, dalla Association of American Geographers, dalla UCGIS (University Consortium for Geographic Information Science, dalla United States Geological Survey e dalla Library of Congress. Il tutto nasce nel corso della Geography Awareness Week, terza settimana di novembre che nel 1987 il Presidente degli Stati Uniti Ronald Reagan stabilì dovesse essere dedicata alla diffusione della cultura geografica.

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

IL-12 and IL-23 modulate plasticity of FoxP3+ regulatory T cells in human Leprosy.

Science.gov (United States)

Tarique, Mohd; Saini, Chaman; Naqvi, Raza Ali; Khanna, Neena; Sharma, Alpana; Rao, D N

2017-03-01

Leprosy is a bacterial disease caused by M. leprae. Its clinical spectrum reflects the host's immune response to the M. leprae and provide an ideal model to investigate the host pathogen interaction and immunological dysregulation. Tregs are high in leprosy patients and responsible for immune suppression of the host by producing IL-10 and TGF-β cytokines. In leprosy, plasticity of Tregs remain unstudied. This is the first study describing the conversion of Tregs into Th1-like and Th17-like cells using in vitro cytokine therapy in leprosy patients. Peripheral blood mononuclear cells from leprosy patients were isolated and stimulated with M. leprae antigen (MLCwA), rIL-12 and rIL-23 for 48h. Expression of FoxP3 in CD4 + CD25 + Tregs, intracellular cytokines IFN-γ, TGF-β, IL-10 and IL-17 in Tregs cells were evaluated by flow cytometry (FACS) after stimulation. rIL-12 treatment increases the levels of pStat4 in Tregs and IFN-γ production. In the presence of rIL-23, pStat3 + and IL-17A + cells increase. rIL-12 and r-IL-23 treatment downregulated the FoxP3 expression, IL-10 and TGF-β production by Tregs and enhances the expression of co-stimulatory molecules (CD80, CD86). In conclusion rIL-12 converts Tregs into IFN-γ producing cells through STAT-4 signaling while rIL-23 converts Tregs into IL-17 producing cells through STAT-3 signaling in leprosy patients. This study may helpful to provide a new avenue to overcome the immunosuprression in leprosy patients using in vitro cytokine. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Dialogo su psicoanalisi e poesia (1946

Directory of Open Access Journals (Sweden)

Benedetto Croce

2013-02-01

Full Text Available Nel 1946 “La Fiera letteraria” ospitò due importanti interventi dedicati a psicoanalisi e poesia. Il primo, per mano nientemeno che di Benedetto Croce, era una lettera di poche pagine, di sostanziale chiusura nei confronti delle pretese novità e originalità del “freudismo” soprattutto in ambito filosofico. Il secondo era la risposta, molto più dettagliata e articolata di un poeta come Umberto Saba, che invece alla psicoanalisi (e non solo come terapia credeva e teneva molto. Riproponiamo qui questi due testi, preceduti da altri due brevi interventi di Croce sulla psicoanalisi: il primo è una recensione alla traduzione francese del testo di Freud sul sogno del 1903; il secondo è una critica sprezzante nei confronti della “cosiddetta critica stilistica”, che viene messa in relazione al metodo Montessori e appunto alla psicoanalisi. 

Expressions of TNF-α, IL-1α and IL-6 in bronchiolar epithelium after thoracic irradiation

International Nuclear Information System (INIS)

Yang Kunyu; Hu Yu; Ruebe Claudia; Ruebe Christian

2006-01-01

Objective: To investigate temporal and spatial releases of proinflam matory cytokines TNF-α, IL-1α and IL-6 in the lung tissue after thoracic irradiation in C57BL/6J mice. Methods: Mice were irradiated with 12 Gy to whole lungs, and control mice were sham-irradiated. Mice were sacrificed at hours 0.5, 1, 3, 6, 12, 24, 48 and 72 and weeks 1, 2, 4, 8, 16 and 24 after thoracic irradiation or sham-irradiation. Expressions of TNF-a and IL-1α, IL-6 proteins were detected with immuno-histochemistry. Results: At hour 6 after thoracic irradiation, the expression of TNF-α protein increased significantly, and at hour 12 after thoracic irradiation, the expressions of IL-1α and IL-6 proteins increased significantly, too. The bronchiolar epithelium was the most prominent source of these inflammatory cytokines in the first hours. During the stage of acute pneumonitis, the bronchiolar epithelium, as well as inflammatory cells in the lung interstitium, produced high amounts of TNF-α, IL-1α and IL-6. Conclusions: It was demonstrated that immediate expressions of TNF-α, IL-1α and IL-6 occurred in the bronchiolar epithelium after lung irradiation, and a long-lasting release by the bronchiolar and alveolar epithelium, and inflammatory cells during acute pneumonitis. Therefore, the bronchiolar epithelium is a significant source of proinflammatory cytokines capable of promoting inflammation through recruitment and activation of inflammatory cells after lung irradiation. (authors)

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.

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.

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 ...

Polymorphic variations in IL-1β, IL-6 and IL-10 genes, their circulating serum levels and breast cancer risk in Indian women.

Science.gov (United States)

Pooja, Singh; Chaudhary, Preeti; Nayak, Lakshma V; Rajender, Singh; Saini, Karan Singh; Deol, Debashish; Kumar, Sandeep; Bid, Hemant Kumar; Konwar, Rituraj

2012-10-01

Cytokines are known as important regulators of the entire gamut of cancer from initiation, invasion and metastasis. This fact and plethora of gene polymorphism data prompted us to investigate cytokine gene polymorphisms in breast cancer (BC) patients. Selected polymorphisms in the IL-1β [-511 T>C (rs16944) and +3954 C>T (rs1143634)]; IL-6 [-174 G>C (rs1800795)]; IL-10 [-1082 A>G (rs1800896), -819 T>C (rs1800871) and -592 A>C (rs1800872)] genes were genotyped in 200 BC patients and 200 healthy volunteers in a case-control study using PCR-RFLP and direct DNA sequencing techniques. Peripheral cytokine levels were measured using ELISA. Allele and genotype data were analyzed for significance of differences between cases and controls using Chi-Square [χ(2)] test. Two sided P-values of less than 0.05 were considered to be statistically significant. Peripheral level of all three cytokines did not show any significant difference between cases and controls. Allele and genotype frequency of IL-1β [-511 T>C (rs16944)] did not show any difference between cases and controls. On the other hand mutant allele and genotype at IL-1β [+3954 C>T (rs1143634)] associated with increased risk of BC. This was also true for pre-menopausal cases and for mutant genotype in post-menopausal cases. Mutant allele and genotypes at IL-6 [-174 G>C (rs1800795)] appeared to be protective in nature such that controls had a higher frequency of both mutant alleles and genotypes. None of the three SNPs in IL-10 gene associated with risk of BC, except significant association of mutant allele and genotypes of -1082 A>G (rs1800896) polymorphism with postmenopausal BC. Mutant allele and genotype at IL-1β [+3954 C>T (rs1143634)] site associated with increased BC risk, while mutant allele and genotypes at IL-6 [-174 G>C (rs1800795)] polymorphism appeared to be protective. Also, there was significant association of mutant allele and genotypes of IL-10 [-1082 A>G (rs1800896)] with postmenopausal BC. None of

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

African Journals Online (AJOL)

Win-07

IL17A and IL17F were significantly higher in asthma patients compared to controls [IL17A: 1.112 (2.088) vs 0.938 ... Asthma is a frequently encountered chronic airway in- ... transcription was performed, in 20 μl reaction volume using the.

Il fiore e la pietra

OpenAIRE

Hirsch, Debora

2012-01-01

Il fiore e la pietra è un progetto di scultura urbana per una piazza della città di Torino. Il tema trae la sua prima ispirazione dal fumetto B.C. di Johnny Hart: un fragile fiore dialoga con una pietra. Lʼambiguità tra solidità e fragilità è simbolicamente accostata alla situazione avversa in cui si trova lʼindustria torinese per eccellenza, FIAT, e al problema dei quartieri dormitori. Il contesto nel quale venne realizzato il progetto è tuttora sintomatico di una situazione ...

Type I IL-1 Receptor (IL-1RI as Potential New Therapeutic Target for Bronchial Asthma

Directory of Open Access Journals (Sweden)

Jyh-Hong Lee

2010-01-01

Full Text Available The IL-1R/TLR family has been receiving considerable attention as potential regulators of inflammation through their ability to act as either activators or suppressors of inflammation. Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness, allergic inflammation, elevated serum total, allergen-specific IgE levels, and increased Th2 cytokine production. The discovery that the IL-1RI–IL-1 and ST2–IL-33 pathways are crucial for allergic inflammation has raised interest in these receptors as potential targets for developing new therapeutic strategies for bronchial asthma. This paper discusses the current use of neutralizing mAb or soluble receptor constructs to deplete cytokines, the use of neutralizing mAb or recombinant receptor antagonists to block cytokine receptors, and gene therapy from experimental studies in asthma. Targeting IL-1RI–IL-1 as well as ST2–IL-33 pathways may promise a disease-modifying approach in the future.

Serum IL-10, IL-17 and IL-23 levels as "bioumoral bridges" between dyslipidemia and atopy.

Science.gov (United States)

Manti, S; Leonardi, S; Panasiti, I; Arrigo, T; Salpietro, C; Cuppari, C

2017-11-01

Although several studies suggest a possible link between dyslipidemia and atopy, literature findings are still unclear. The aim of the study was to investigate the relationship between dyslipidemia and atopy in a pediatric population affected by dyslipidemia or dyslipidemia/atopic predisposition. Children with dyslipidemia, dyslipidemia and atopy as well as healthy children were recruited. Serum total IgE, IL-10, IL-17, and IL-23 levels as well as fasting lipid values (total cholesterol, LDL, HDL and triglycerides) were performed on all enrolled children. The present study evaluated 23 patients affected by dyslipidemia, 26 patients affected by atopy and dyslipidemia and, 22healthy children. Serum total IgE levels significantly related also with serum cholesterol levels: positively with total cholesterol (pdyslipidemia than patients with dyslipidemia (pdyslipidemia than patients with dyslipidemia (pdyslipidemia and atopic predisposition share the same immune pathways as well as they offer new insights in the complex crosstalk between hyperlipidemia and atopy. Copyright © 2017 Elsevier Ltd. All rights reserved.

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. 

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.

[Plasma IL-18 levels are related to insulin and are modulated by IL-18 gene polymorphisms].

Science.gov (United States)

Martinez-Hervas, Sergio; Martínez-Barquero, Vanesa; Nuñez Savall, Ester; Lendínez, Verónica; Olivares, Laura; Benito, Esther; Real, Jose T; Chaves, F Javier; Ascaso, Juan F

2015-01-01

Atherosclerosis is an inflammatory chronic disease influenced by multiple factors. Different prospective studies have shown that plasmatic levels of inflammatory markers were related to atherosclerosis and cardiovascular disease. To evaluate whether plasmatic levels of interleukin 18 (IL-18) are modulated by SNPs (single nucleotide polymorphisms) of the IL 18 gene and its possible association with insulin levels and other cardiovascular risk factors. 746 individuals were studied for a period of two years by opportunistic selection in the metropolitan area of Valencia. Parameters of lipid and glucose metabolism were analyzed by standard methodology. IL-18 was measured by ELISA. Individuals with insulin resistance showed significant higher levels of IL-18. IL 18 was significantly correlated with insulin levels and other cardiovascular risk factors. The CC genotype of the rs1834481 SNP was significantly associated with lower levels of IL-18. However, the GG genotype of the rs7559479 was associated with significant higher levels of IL-18. IL-18 is associated with insulin resistance and other cardiovascular risk factors, being those levels genetically regulated. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

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

Tra il mediterraneo e il fonte battesimale: Musulmani a Napoli nel XVI secolo

OpenAIRE

Varriale, Gennaro

2013-01-01

Il saggio analizza la presenza di musulmani a Napoli durante il Cinquecento, quando la capitale vive una profonda trasformazione urbanistica, che è vincolata alla immigrazione di comunità esogene e al conflitto contro il Turco. Le ostilità tra la Casa d’Austria e la Sublime Porta condizionano inevitabilmente la vita dei maomettani, che appartengono a tre grandi categorie: schiavi, franchi o esuli. Secondo la propria condizione gli islamici occupano diversi spazi cittadini. I musulmani di Napo...

Emissions monitoring in conveyed gas flow: (a) sulfur oxides and nitrogen oxides expressed respectively as SO{sub 2} and NO{sub 2}, (b) inorganic chlorine and fluorine compounds as gases and vapours expressed as HCl and HF; Rilevamento delle emissioni in flussi gassosi convogliati: (a) ossidid di zolfo e ossidi di azoto espressi rispettivamente come SO{sub 2} e NO{sub 2}, (b) composti inorganici del cloro e del fluoro sotto forma di gas e vapore espressi rispettivamente come HCl e HF

Energy Technology Data Exchange (ETDEWEB)

Ziemacki, G.; Viviano, G. [ed.] [Isituto Superiore di Sanita`, Rome (Italy). Gruppo di lavoro `Modifiche per il rilevamento delle emissioni in atmosfera da impianti industriali`

1998-03-01

The method (a) enables the determination of sulfur oxides (SO{sub 2}) and nitrogen oxides (NO{sub 2}) in conveyed atmospheric emissions. A stream of flue gas is a sampled by a heated with a filter housing and absorbed by an alkaline solution of potassium permanganate. The absorption solution is analyzed by ion-exchange chromatography for the determination of sulfate ion and nitrate ion as SO{sub 2} and NO{sub 2}. The method (b) enables the determination of hydrochloric acid (HCl) and hydrofluoric acid (HF) in conveyed atmospheric emissions. A stream of flue gas is sampled by a heated probe with a filter housing and absorbed by an alkaline solution (NaOH). The absorption solution is analyzed by ion-exchange chromatography for the determination of chloride ion and fluoride ion as HCl and HF. [Italiano] Il metodo a) consente la determinazione, in emissioni atmosferiche convogliate, degli ossidi di zolfo (SO{sub 2}) e degli ossidi di azoto (NO{sub 2}). Il campionamento viene effettuato mediante sonda riscaldata, munita di sistema filtrante, e sistema di assorbimento in soluzione alcalina di permanganato di potassio. La soluzione di assorbimento viene analizzata mediante cromatografia a scambio ionico, determinando le concentrazioni di ioni solfato e nitrato come SO{sub 2} ed NO{sub 2}. Il metodo b) consente la determinazione, in emissioni atmosferiche convogliate, dell`acido cloridrico (HCl) e dell`acido fluoridrico (HF). Il campionamento viene effettuato mediante sonda riscaldata, munita di sistema filtrante, e sistema di assorbimento in soluzione alcalina (NaOH). La soluzione alcalina viene quindi analizzata mediante cromatografia a scambio ionico, deter,mminando le concentrazioni di ioni cloro e fluoro come HCl e HF.

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

Science.gov (United States)

Wilasco, Maria Ines de Albuquerque; Uribe-Cruz, Carolina; Santetti, Daniele; Fries, Gabriel Rodrigo; Dornelles, Cristina Toscani Leal; Silveira, Themis Reverbel da

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. 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. 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 (patresia, 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. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Association between the IL1B (-511), IL1B (+3954), IL1RN (VNTR) polymorphisms and Graves' disease risk: a meta-analysis of 11 case-control studies.

Science.gov (United States)

Chen, Min-Li; Liao, Ning; Zhao, Hua; Huang, Jian; Xie, Zheng-Fu

2014-01-01

Data on the association between the interleukin-1 (IL-1) gene polymorphisms and Graves' disease (GD) risk were conflicting. A meta-analysis was undertaken to assess this association. We searched for case-control studies investigating the association between the IL1B (-511), IL1B (+3954), IL1RN (VNTR) polymorphisms and GD risk. We extracted data using standardized forms and calculated odds ratios (OR) with 95% confidence intervals (CI). A total of 11 case-control studies were included in this meta-analysis. Available data indicated that the IL1B (-511) polymorphism was associated with GD risk in the overall populations (Caucasians and Asians) in homozygote model (TT vs. CC, OR = 0.86, 95% CI: 0.76-0.97, Pz  = 0.015), but not in dominant and recessive models (TT+TC vs. CC: OR = 0.95, 95% CI: 0.81-1.12, Pz  =  0.553 and TT vs. TC+CC: OR = 0.82, 95% CI: 0.60-1.12, Pz  =  0.205, respectively). No association between the IL1B (+3954), IL1RN (VNTR) polymorphisms and GD risk was found in the overall populations in any of the genetic models. In subgroup analyses according to ethnicity, the IL1B (-511) polymorphism was associated with GD risk in Asians in recessive and homozygote models (TT vs. TC+CC: OR =  0.68, 95% CI: 0.55-0.84, Pz VNTR) polymorphisms and GD risk was indicated in Asians, and we found no association between the IL1B (-511), IL1B (+3954), IL1RN (VNTR) polymorphisms and GD risk in Caucasians in any of the genetic models. The IL1B (-511) polymorphism, but not the IL1B (+3954) and IL1RN (VNTR) polymorphisms was associated with GD risk in Asians. There was no association between these polymorphisms and GD risk in Caucasians.

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.

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.

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

; yet they appear healthy and do not exhibit overt clinical or laboratory abnormalities. We induced comparable levels of aAb-IL-6 in different mouse strains by vaccination with immunogenic IL-6 analogues. We observed that the induced aAb-IL-6 protected against collagen-induced arthritis and experimental...

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

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.

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.

[Effects of canine IL-2 and IL-7 genes on enhancing immunogenicity of canine parvovirus VP2 gene vaccine in mice].

Science.gov (United States)

Chen, Huihui; Zhong, Fei; Li, Xiujin; Wang, Lu; Sun, Yan; Neng, Changai; Zhang, Kao; Li, Wenyan; Wen, Jiexia

2012-11-04

To investigate the effects of canine interleukin-2 (cIL-2) and cIL-7 genes on enhancing the immunogenicity of canine parvovirus (CPV) VP2 DNA vaccine. The bicistronic vectors of cIL-2 and cIL-7 genes were constructed using the eukaryotic expression vector containing internal ribosome entry site (IRES). The cIL-2/ cIL-7 dicistronic vector plus previously constructed vectors, including CPV VP2 DNA vaccine vector, cIL-2 vector and cIL-7 vector, were used to co-immunize mice with different combinations, consisting of VP2 alone, VP2 + cIL-2, VP2 + cIL-7 and VP2 + cIL-2/cIL-7. The VP2-specific antibody levels in immunized mice were measured by ELISA at different time post-immunization. The proliferation indices and interferon-gamma expression were measured by lymphocyte proliferation assay and ELISA, respectively. The cIL-2/cIL-7 bicistronic vector was correct and could mediate cIL-2 and cIL-7 gene expression in eukaryotic cells. Immunization results revealed that the antibody titers and the neutralizing antibody levels of the mice co-immunized with VP2 + cIL-7/cIL-2 vectors were significantly higher than that with either VP2 + cIL-2 vectors or VP2 + cIL-7 vectors (P vaccine.

Lemongrass effects on IL-1beta and IL-6 production by macrophages.

Science.gov (United States)

Sforcin, J M; Amaral, J T; Fernandes, A; Sousa, J P B; Bastos, J K

2009-01-01

Cymbopogon citratus has been widely recognised for its ethnobotanical and medicinal usefulness. Its insecticidal, antimicrobial and therapeutic properties have been reported, but little is known about its effect on the immune system. This work aimed to investigate the in vivo effect of a water extract of lemongrass on pro-inflammatory cytokine (IL-1beta and IL-6) production by macrophages of BALB/c mice. The action of lemongrass essential oil on cytokine production by macrophages was also analysed in vitro. The chemical composition of the extract and the oil was also investigated. Treatment of mice with water extract of lemongrass inhibited macrophages to produce IL-1beta but induced IL-6 production by these cells. Lemongrass essential oil inhibited the cytokine production in vitro. Linalool oxide and epoxy-linalool oxide were found to be the major components of lemongrass water extract, and neral and geranial were the major compounds of its essential oil. Taken together, these data suggest an anti-inflammatory action of this natural product.

Role of IL-1 beta and COX2 in silica-induced IL-6 release and loss of pneumocytes in co-cultures.

Science.gov (United States)

Herseth, Jan I; Refsnes, Magne; Låg, Marit; Schwarze, Per E

2009-10-01

The pro-inflammatory cytokines IL-1 beta, TNF-alpha and IL-6 are of great importance in the development of silica-induced lung damage and repair. In this study we investigated the role of IL-1 beta, TNF-alpha and COX2 in silica-induced regulation of IL-6 release and pneumocyte loss in various mono- and co-cultures of monocytes, pneumocytes and endothelial cells. All co-cultures with monocytes, and especially cultures including endothelial cells, showed an increase of silica-induced release of IL-6 compared to the respective monocultures. Treatment with the antagonist IL-1 ra strongly decreased IL-1 beta and IL-6 release in contact co-cultures of monocytes and pneumocytes. COX2 up-regulation by silica and IL-1 beta was eliminated by IL-1 ra. Inhibition of COX2 markedly reduced both IL-1 beta and IL-6 release. IL-1 ra was more effective than COX2-inhibition in reduction of IL-6, but not of IL-1 beta. Silica-induced pneumocyte loss was reduced by IL-1 beta, but this effect was not counteracted by the IL-1 receptor antagonist. Our findings suggest that silica-induced IL-6 release from pneumocytes is mainly mediated via IL-1 beta release from the monocytes, via both COX2-dependent and -independent pathways. Notably, COX2-derived mediators seem crucial for a positive feed-back regulation of IL-1 beta release from the monocytes. In contrast to silica-induced IL-6, the reduction in pneumocyte loss by IL-1 beta does not seem to be regulated through an IL-1R1-dependent mechanism.

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.

Data Evaluation Problems in the Pulsed Neutron Source Method; Problemes d'Evaluation des Donnees dans les Applications de la Methode de la Source Pulsee; Problemy otsenki dannykh pri primenenii metoda istochnika impul'snykh nejtronov; Problemas de Evaluacion de Datos en el Metodo de la Fuente de Neutrones Pulsados

Energy Technology Data Exchange (ETDEWEB)

Pal, L.; Bod, L.; Szatmary, Z. [Central Research Institute for Physics, Hungarian Academy of Sciences, Budapest (Hungary)

1965-08-15

the weighted least-squares method using the decay constants of minimum standard deviation evaluated from the maximum likelihood function. Since, for the materials investigated, the values of the transport mean free path were not known, a fast converging iteration procedure was elaborated for the determination of the transport mean free path. The computer evaluation made it possible to determine the coefficients of the B{sup 6} and higher order terms of the decay constant. The diffusion parameters of the hydrogenous materials investigated were calculated by the Radkowsky prescription from the energy dependence of the integral scattering cross-sections. The calculations have shown that the Radkowsky prescription is a useful empirical method for the evaluation of the transport mean free path of numerous hydrogenous materials. (author) [French] Pour obtenir les parametres de diffusion des neutrons thermiques, on emploie depuis plus de dix ans la methode des neutrons puises. Cette methode convient tout particulierement pour l'etude des ralentisseurs hydrogenes. Les auteurs donnent les resultats des mesures pour l'eau, le benzene, le toluene, le xylene, le cyclohexane, le n-hexane et le diphenyle et discutent les methodes permettant d'evaluer avec le minimum d'erreurs les parametres de diffusion interessants, a partir des donnees mesurees. Ils etudient en detail au point de vue theorique et experimental l'effet du temps de vol qui se fait sentir lors des recherches sur les ralentisseurs a des temperatures elevees pour des raisons techniques, et influe sur la valeur de la constante de decroissance; ils indiquent les conditions geometriques dans lesquelles on peut obtenir une bonne precision. Ilsdeterminent en outre l'effet du temps mort du detecteur de neutrons et du systeme d'amplification sur la valeur de la constante de decroissance: l'effet du temps mort peut etre neglige si [i(t) {tau}]{sup 2} << 1, ou i (t) dt est le nombre des neutrons detectes dans l'intervalle de

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

Directory of Open Access Journals (Sweden)

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.

Biological significance of soluble IL-2 receptor

Directory of Open Access Journals (Sweden)

Calogero Caruso

1993-01-01

Full Text Available A NUMBER of receptors for growth factors and differentiation antigens have been found to be secreted or released by cells. Following mononuclear cell (MNC activation and interleukin-2 receptor (IL-2R expression, a soluble form of the Alpha;-chain of IL-2R (sIL-2R is released. The sIL-2R has been shown to be present in the culture supernatants of activated MNCs as well as in normal sera and, in higher amounts, in sera from subjects affected by several diseases including neoplastic, infectious and autoimmune ones, and in sera from transplanted patients suffering allograft rejection. The blood sIL-2R levels depend on the number of producing cells and the number of molecules per cell, so that sIL-2R blood values may represent an index of the number and the functional state of producing cells, both normal and neoplastic. Thus, monitoring of the immune system, mostly T-cells and haematological malignancies might be targets for the measurement of sIL-2R. Since many conditions may influence sIL-2R production, little diagnostic use may result from these measurements. However, since blood sIL-2R levels may correlate with disease progression and/or response to therapy, their measurement may be a useful index of activity and extent of disease. The precise biological role of the soluble form of the IL-2R is still a matter of debate. However, we know that increased sIL-2R levels may be observed in association with several immunological abnormalities and that sIL-2R is able to bind IL-2. It is conceivable then that in these conditions the excess sIL-2R released in vivo by activated lymphoid cells or by neoplastic cells may somehow regulate IL-2-dependent processes. On the other hand, it cannot exclude that sIL-2R is a by-product without biological significance. Finally, it is puzzling that in many conditions in which an increase of blood sIL-2R values has been observed, MNCs display a decreased in vitro capacity to produce sIL-2R. These seemingly contrasting

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)

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

International Nuclear Information System (INIS)

Liang Zhenming; Liu Xia

2005-01-01

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

IL-1α Up-Regulates IL-6 Expression in Bovine Granulosa Cells via MAPKs and NF-κB Signaling Pathways

Directory of Open Access Journals (Sweden)

Meng Yang

2017-01-01

Full Text Available Background/Aims: IL-6 is one of the main cytokines in regulating ovarian follicular development and ovulation. However, the factors that regulate IL-6 expression in follicles are still unclear. The aim of this study was to elucidate the mechanisms underlying the effect of IL-1α on IL-6 expression in granulosa cells. Methods: IL-6 expression after IL-1α with/without inhibitors treatment was analyzed by RT-qPCR and ELISA. The phosphorylation of proteins induced by IL-1α was analyzed by western blot. The intracellular cAMP level was assayed by immunoassay kit. Results: IL-1α has a dose-dependent effect on IL-6 expression in granulosa cells. This promoting effect can be significantly attenuated by Erk, c-Jun, p38 and IκB proteins inhibitors, respectively. Moreover, the phosphorylation levels of Erk, c-Jun, p38 and IκBα proteins were significantly increased after IL-1α treatment. In addition, we also found that IL-1α not only reversed the cAMP attenuated IL-6 expression， but also increased IL-1α mRNA expression in granulosa cells. Conclusion: The regulation of IL-1α on IL-6 expression is mediated by activation of MAPKs and NF-κB signaling pathways. Moreover，IL-1α may regulate the ovulation-related genes expression in granulosa cells by an autocrine and/or paracrine manner.

Il degrado abusivo e il "degrado legale" del territorio: gli ecomostri

Directory of Open Access Journals (Sweden)

Anna Cicchetti

2010-07-01

Full Text Available Il fenomeno di una urbanizzazione senza criteri né misure, collegata a ragioni turistiche, molto spesso opportunistiche, è affrontato dalla giurisprudenza nella sua azione di controllo del territorio: ne sono un caso esemplare gli “ecomostri”, ormai comunemente e tristemente sono conosciuti dalla società civile. Queste costruzioni di grande impatto territoriale, ambientale e paesaggistico, in alcuni casi sono legittimati da interventi normativi non bene soppesati e in altri avvengono in maniera c.d. abusiva, con l’unica conseguenza, in entrambe le ipotesi, di deturpare l’ambiente circostante sotto molteplici profili, non ultimo quello incidente su località turistiche. Il contributo si pone l’obiettivo di contribuire ad una politica turistica attenta al profilo ambientale: occorre individuare una maggiore cogenza e conoscenza normativa a favore di una pianificazione urbanistica e politica del paesaggio, in grado di sostenere il recupero, la riqualificazione e valorizzazione delle bellezze naturali presenti sul territorio. Solo il coinvolgimento e la necessaria collaborazione di tutti i soggetti del territorio per una programmazione orientata a realizzare uno «sviluppo capace di rispondere ai bisogni delle generazioni attuali, senza compromettere la capacità delle generazioni future di rispondere ai propri».

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.

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

Science.gov (United States)

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

2011-07-01

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

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)

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

. Further, IL-1R antagonism improves normoglycemia and ß-cell function in type 2 diabetic patients. Inhibition of lysine deacetylases (KDACi) counteracts ß-cell toxicity induced by the combination of IL-1 and IFN¿ and reduces diabetes incidence in non-obese diabetic (NOD) mice. We hypothesized that KDACi......Aims: Pro-inflammatory cytokines and chemokines, in particular IL-1ß, IFN¿, and CXCL10, contribute to ß-cell failure and loss in DM via IL-1R, IFN¿R, and TLR4 signaling. IL-1 signaling deficiency reduces diabetes incidence, islet IL-1ß secretion, and hyperglycemia in animal models of diabetes...

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...

The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma.

Science.gov (United States)

Stronach, Euan A; Cunnea, Paula; Turner, Christina; Guney, Tankut; Aiyappa, Radhika; Jeyapalan, Senthuran; de Sousa, Camila H; Browne, Alacoque; Magdy, Nesreen; Studd, James B; Sriraksa, Ruethairat; Gabra, Hani; El-Bahrawy, Mona

2015-10-13

Platinum based drugs are the cornerstone of chemotherapy for ovarian cancer, however the development of chemoresistance hinders its success. IL-8 is involved in regulating several pro-survival pathways in cancer. We studied the expression of IL-8 and IL-8 receptors in platinum sensitive and resistant cell lines. Using qRT-PCR and immunohistochemistry, both platinum sensitive (PEA1, PEO14) and resistant (PEA2, PEO23) show increased expression of IL-8 and IL-8 receptors. IL-8RA shows nuclear and cytoplasmic expression, whilst IL-8RB is present solely in the cytoplasm. Knockdown of IL-8 increased sensitivity to cisplatin in platinum sensitive and reversed platinum resistance in resistant cell lines, decreased the expression of anti-apoptotic Bcl-2 and decreased inhibitory phosphorylation of pro-apoptotic Bad. IL-8 receptor antagonist treatment also enhanced platinum sensitivity. Nuclear localisation of IL-8RA was only detected in platinum resistant tumours. Inhibition of IL-8 signalling can enhance response in platinum sensitive and resistant disease. Nuclear IL-8RA may have potential as a biomarker of resistant disease.

Oral Escherichia coli Colonization Factor Antigen I (CFA/I) Fimbriae Ameliorate Arthritis via IL-35, not IL-27

Science.gov (United States)

Kochetkova, Irina; Thornburg, Theresa; Callis, Gayle; Holderness, Kathryn; Maddaloni, Massimo; Pascual, David W.

2014-01-01

A Salmonella therapeutic expressing enterotoxigenic E. coli colonization factor antigen I (CFA/I) fimbriae protects against collagen-induced arthritis (CIA) by eliciting two regulatory T cell (Treg) subsets: TGF-β-producing Foxp3−CD39+CD4+ and IL-10-producing Foxp3+CD39+CD4+ T cells. However, it is unclear if CFA/I fimbriae alone are protective, and if other regulatory cytokines are involved especially in the context for the EBI3-sharing cytokines, Treg-derived IL-35 and APC-derived IL-27, both capable of suppressing Th17 cells and regulating autoimmune diseases. Subsequent evaluation revealed that a single oral dose of purified, soluble CFA/I fimbriae protected against CIA as effectively as Salmonella-CFA/I, and found Foxp3+CD39+CD4+ T cells as the source of secreted IL-35, whereas IL-27 production by CD11c+ cells was inhibited. Inquiring into their relevance, CFA/I fimbriae-treated IL-27 receptor-deficient (WSX-1−/−) mice were equally protected against CIA as wild-type mice suggesting a limited role for IL-27. In contrast, CFA/I fimbriae-mediated protection was abated in EBI3−/− mice accompanied by the loss of TGF-β- and IL-10-producing Tregs. Adoptive transfer of B6 CD39+CD4+ T cells to EBI3−/− mice with concurrent CFA/I plus IL-35 treatment effectively stimulated Tregs suppressing proinflammatory CII-specific Th cells. Opposingly, recipients co-transferred with B6 and EBI3−/− CD39+CD4+ T cells and treated with CFA/I plus IL-35 failed in protecting mice implicating the importance for endogenous IL-35 to confer CFA/I-mediated protection. Thus, CFA/I fimbriae stimulate IL-35 required for the co-induction of TGF-β and IL-10. PMID:24337375

IL-33 and IgE stimulate mast cell production of IL-2 and regulatory T cell expansion in allergic dermatitis.

Science.gov (United States)

Salamon, P; Shefler, I; Moshkovits, I; Munitz, A; Horwitz Klotzman, D; Mekori, Y A; Hershko, A Y

2017-11-01

We have previously shown that mast cells (MCs) suppress chronic allergic dermatitis in mice. The underlying mechanism involves MC-derived IL-2, which supports regulatory T cell (Treg) response at the site of inflammation. However, it is not clear what are the factors that drive MCs to produce IL-2. To understand the mechanisms that lead to IL-2 production from MCs in chronic allergic dermatitis. Isolated murine bone marrow-derived MCs (BMMCs) were incubated with various stimulators, and IL-2 production was assessed by RT-PCR and ELISA. The response of signalling pathways was evaluated by MAPK inhibitors and Western blot analysis. The effect of MC-IL-2 on Tregs was studied by incubation of splenic T cells with conditioned media obtained from activated BMMCs. Dermatitis was elicited by repeated exposures of mouse ears to oxazolone. MCs in mouse and human skin samples were evaluated by immunostaining. BMMCs released IL-2 in response to IL-33, and IL-2 production was further enhanced by concomitant FcεRI activation. The effect of IL-33 was mediated by activation of the MAPK family members. IL-2 in conditioned media from IL-33 and IgE-stimulated BMMCs led to considerable expansion of Tregs in vitro. IL-33 levels were elevated in oxazolone-challenged ears along with increased numbers of IL-2-expressing MCs. Human skin with chronic inflammation also contained IL-2-expressing MCs that colocalized with IL-33 staining in the dermis. IL-33, in collaboration with IgE, is critical for MC-IL-2 production in allergic skin disease, thus leading to Treg stimulation and suppression of allergic dermatitis. © 2017 John Wiley & Sons Ltd.

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.

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.

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...

Clinical significance of determination of levels of several cytokines (IL-1β, IL-2, IL-10 and TNF) in expressed prostatic fluid (EPS) from patients with various types of chronic prostatitis

International Nuclear Information System (INIS)

Gao Juxing; Zhang Jiyun

2006-01-01

Objective: To investigate the levels of several cytokines in EPS from patients with different types of chronic prostatitis. Methods: The EPS levels of IL-1β, IL-2, IL-10 and TNF were determined with RIA in 86 patients with various types of chronic prostatitis as well as in 30 controls. Results: The EPS levels of IL-1β, IL-2 and TNF in all the 86 patients with various types of chronic prostatitis were significantly higher than those in the controls (P 10/HP, lecithin body < + +) (n=31) were significantly higher than those in patients with CPPS IIIB (WRC < 10/HP, lecithin body normal, n=29)(P<0.05 or P<0.01 ), while the IL-10 levels were significantly lower (P<0.01). Conclusion: EPS levels of the cytokines IL-β, IL-2, TNF and IL-10 might be of value for diagnosis and classification of chronic prostatitis. (authors)

IL-32 promotes angiogenesis

NARCIS (Netherlands)

Nold-Petry, C.A.; Rudloff, I.; Baumer, Y.; Ruvo, M.; Marasco, D.; Botti, P.; Farkas, L.; Cho, S.X.; Zepp, J.A.; Azam, T.; Dinkel, H.; Palmer, B.E.; Boisvert, W.A.; Cool, C.D.; Taraseviciene-Stewart, L.; Heinhuis, B.; Joosten, L.A.; Dinarello, C.A.; Voelkel, N.F.; Nold, M.F.

2014-01-01

IL-32 is a multifaceted cytokine with a role in infections, autoimmune diseases, and cancer, and it exerts diverse functions, including aggravation of inflammation and inhibition of virus propagation. We previously identified IL-32 as a critical regulator of endothelial cell (EC) functions, and we

Maternal Genetic Variants of IL4/IL13 Pathway Genes on IgE With "Western or Eastern Environments/Lifestyles".

Science.gov (United States)

Zhang, Guicheng; Khoo, Siew-Kim; Mäkelä, Mika J; Candelaria, Pierre; Hayden, Catherine M; von Hertzen, Leena; Laatikainen, Tiina; Vartiainen, Erkki; Goldblatt, Jack; Haahtela, Tari; LeSouëf, Peter N

2014-07-01

We investigated maternal genetic effects of four IL-4/IL-13 pathway genes as well as their interactions with the "Western or Eastern lifestyles/environments" on IgE in Karelian children. This study included 609 children and their mothers. Total IgE levels in children and mothers were measured and 10 single nucleotide polymorphisms (SNPs) in IL-4, IL-4Ra, IL-13, and STAT6 were genotyped in mothers and their children. The maternal G allele of IL-13 130 (rs20541) was significantly (P=0.001) associated with decreased IgE in children in the Karelian population (Pooling Finnish and Russian children), as well as in Finnish (P=0.030) and Russian children (P=0.018). The IgE levels were significantly (P=0.001) higher in Russian children whose mothers were homozygous for the G allele of the IL-4Ra 50 (rs1805010) SNP than that in Russian children of mothers who were AG heterozygotes or AA homozygotes. After accounting for children's genotypes, we observed interactive effects on children's IgE for maternal IL-13 130 genotypes (P=0.014) and maternal IL-4Ra 50 genotypes (P=0.0003) with "Western or Eastern" lifestyles/environments. With the adjustment for multiple comparisons using a false discovery rate (FDR) of 0.05, the interactive effect of the maternal IL-4Ra50 SNP was significant. Maternal genetic variants in IL-4/IL-13 pathway genes, such as IL-13 130 and IL-4Ra50, influenced IgE levels in school children that were independent of the children's genetic effects. These effects differ in "Western or Eastern" environments.

IL DUELLO NEL RINASCIMENTO E IL RIPENSAMENTO ETICO SUL DUELLO DI FRANCESCO PATRIZI

Directory of Open Access Journals (Sweden)

Fulvio Šuran

2012-01-01

Full Text Available In questa prima parte del saggio ci soff ermeremo in modo particolare al periodo che intercorre tra la seconda metà del XV secolo e la prima metà del XVI secolo, in quanto è in questo lasso di tempo che si trovano serie e chiare testimonianze riguardanti la questione del duello. E questo sia nelle opere letterarie che in quelle riguardanti la precettistica. Per quanto riguarda quelle di precettistica, oltre al gran numero di trattati, è da tener presente anche il gran numero delle loro riedizioni, specialmente di quelli più famosi. Dove, oltre all'immancabile comunanza d’interessi fra poeti epici e trattatisti del duello, si noterà anche una sostanziale identità terminologica - per esempio sia i poeti sia i trattatisti ritengono che il duello sia una ‘prova’ di giudizio fi nale. Questo non comporta, nel contempo, una convergenza di convinzioni fi losofi che, in quanto, come si vedrà, il duello letterario diff erisce da quello reale proprio per la sua diversa comprensione fi losofi ca del combattere. Pertanto con la presente relazione si cercherà di dispiegare la problematica che questo istituto di per sé ha comportato nel periodo storico preso in considerazione. Il duello infatti si configurava come una questione sociale tutt'altro che irrilevante per la sua connotazione ambivalente di ordalia – quale forma particolare di rapporto fra uomo e sacro – e di inculpata tutela – quale forma particolare di ricorso alla violenza privata a tutela di un fondamentale diritto naturale. In tutti e due i casi si tratta di una forma di onore, sia individuale sia nobiliare, del quale il Patrizi ne discuterà la fondatezza interpretandolo specialmente in qualità di virtù. In questa defi nizione dell'onore – che il Patrizi aff ronta con un gusto platonico – si possono scorgere questioni di alta portata politica, che ponevano sotto varia forma la questione dei rapporti tra individuo e Stato. In tal modo il duello d’onore assumeva un

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

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

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.

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....

Occupational Exposure to Trichloroethylene and Serum Concentrations of IL-6, IL-10, and TNF-alpha

Science.gov (United States)

Bassig, Bryan A.; Zhang, Luoping; Tang, Xiaojiang; Vermeulen, Roel; Shen, Min; Smith, Martyn T.; Qiu, Chuangyi; Ge, Yichen; Ji, Zhiying; Reiss, Boris; Hosgood, H. Dean; Liu, Songwang; Bagni, Rachel; Guo, Weihong; Purdue, Mark; Hu, Wei; Yue, Fei; Li, Laiyu; Huang, Hanlin; Rothman, Nathaniel; Lan, Qing

2015-01-01

To evaluate the immunotoxicity of trichloroethylene (TCE), we conducted a cross-sectional molecular epidemiology study in China of workers exposed to TCE. We measured serum levels of IL-6, IL-10, and TNF-α, which play a critical role in regulating various components of the immune system, in 71 exposed workers and 78 unexposed control workers. Repeated personal exposure measurements were taken in workers before blood collection using 3 M organic vapor monitoring badges. Compared to unexposed workers, the serum concentration of IL-10 in workers exposed to TCE was decreased by 70% (P = 0.001) after adjusting for potential confounders. Further, the magnitude of decline in IL-10 was >60% and statistically significant in workers exposed to <12 ppm as well as in workers with exposures ≥ 12 ppm of TCE, compared to unexposed workers. No significant differences in levels of IL-6 or TNF-α were observed among workers exposed to TCE compared to unexposed controls. Given that IL-10 plays an important role in immunologic processes, including mediating the Th1/Th2 balance, our findings provide additional evidence that TCE is immunotoxic in humans. PMID:23798002

Ginger Extract Reduces the Expression of IL-17 and IL-23 in the Sera and Central Nervous System of EAE Mice.

Science.gov (United States)

Jafarzadeh, Abdollah; Azizi, Sayyed-Vahab; Nemati, Maryam; Khoramdel-Azad, Hossain; Shamsizadeh, Ali; Ayoobi, Fatemeh; Taghipour, Zahra; Hassan, Zuhair Mohammad

2015-12-01

IL-17/IL-23 axis plays an important role in the pathogenesis of several autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). The immunomodulatory properties of ginger are reported in previous studies. To evaluate the effects of ginger extract on the expression of IL-17 and IL-23 in a model of EAE. EAE was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein and then treated with PBS or ginger extracts, from day +3 to +30. At day 31, mice were scarificed and the expression of IL-17 and IL-23 mRNA in spinal cord were determined by using real time-PCR. The serum levels of cytokines were measured by ELISA. The mRNA expression of IL-17, IL-23 P19 and IL-23 P40 in CNS and serum levels of IL-17 and IL-23 were significantly higher in PBS-treated EAE mice than non-EAE group (pginger-treated EAE mice the mRNA expression of IL-17, P19 and P40 in CNS and serum IL-23 levels were significantly decreased as compared to PBS-treated EAE mice (pginger-treated EAE group had significantly lower expression of IL-17, P19 and P40 in CNS and lower serum IL-17 and IL-23 levels than PBS-treated EAE group (pGinger extract reduces the expression of IL-17 and IL-23 in EAE mice. The therapeutic potential of ginger for treatment of MS could be considered in further studies.

Clinical significance of changes of serum gas, IL-6 and IL-10 levels after treatment in patients with peptic ulcer

International Nuclear Information System (INIS)

Ye Yuexian

2009-01-01

Objective: To explore the clinical significance of changes of serum Gas, Interleukin-6(IL-6) and Interleukin-10(IL-10) levels in patients with peptic ulcer. Methods: Serum Gas, IL-6 and IL-10 (with RIA) levels were determined in 61 patients with peptic ulcer both before and after treatment as well as in 35 controls. Results: Before treatment the serum Gas, IL-6 and IL-10 levels were significantly higher in the patients with peptic ulcer than those in controls (P 0.05). Conclusion: Serum Gas, IL-6 and IL-10 levels were closely related to the diseases process of peptic ulcer and were of prognostic values. (authors)

IL-36 cytokines in autoimmunity and inflammatory disease.

Science.gov (United States)

Ding, Liping; Wang, Xiaohui; Hong, Xiaoping; Lu, Liwei; Liu, Dongzhou

2018-01-05

The inteleukin-36 (IL-36) cytokines include IL-36α, IL-36β, IL-36γ and IL-36Ra, which belong to the IL-1 family and exert pro-inflammatory effects on various target cells such as keratinocytes, synoviocytes, dendritic cells and T cells. Emerging evidence has suggested a role of IL-36 in the pathogenesis of many inflammatory diseases. Here, we provide a brief review on the activation of IL-36 family cytokines and their involvement in autoimmunity and inflammatory diseases, which will provide further insights in understanding the functions of IL-36 family cytokines in the pathophysiology of autoimmunity and inflammatory diseases.

Evaluation of IL-1β, IL-1ra, and IL-10 levels and outcome of periodontal therapy in chronic periodontitis with familial Mediterranean fever.

Science.gov (United States)

Bostanci, Vildan; Toker, Hulya; Senel, Soner; Poyraz, Omer; Akpinar, Aysun; Görgün, Emine Pirim; Bakar, Olcay

2017-01-01

This study aimed to examine the IL-1β, IL-1ra, and IL-10 cytokine levels in gingival crevicular fluid (GCF) and serum of familial Mediterranean fever (FMF) and chronic periodontitis (CP) patients, and their response to nonsurgical periodontal therapy. A total of 50 patients, 15 FMF patients with generalized chronic periodontitis (FMF-CP), 15 systemically healthy patients with generalized chronic periodontitis (CP), ten systemically and periodontal healthy controls (HC), and ten periodontally healthy FMF patients (FMF-HC) were enrolled in the study. The cytokine levels in GCF and serum were determined by ELISA. Probing depth, clinical attachment level, and gingival and plaque indices in each participant were also measured. The GCF and clinical parameters at baseline and 6 weeks were recorded. The study indicated statistically significant healing of the clinical parameters in both FMF-CP and CP groups after periodontal treatment. GCF IL-1β levels at 6 weeks in FMF-CP group were significantly lower than the CP group (p  0.05). The results of our study suggested that there was a positive correlation between gingival inflammation and serum cytokine levels in FMF patients and also colchicine treatment showed protective effects on GCF cytokine levels in FMF-CP group. Following treatment, GCF IL-1β and GCF IL-1ra levels were decreased in FMF-CP group. GCF IL-10 levels were increased in FMF-CP group compared to other groups. Also, the serum cytokine levels associated with periodontal inflammation in FMF patients.

Efficacy of melatonin, IL-25 and siIL-17B in tumorigenesis-associated properties of breast cancer cell lines.

Science.gov (United States)

Gelaleti, Gabriela Bottaro; Borin, Thaiz Ferraz; Maschio-Signorini, Larissa Bazela; Moschetta, Marina Gobbe; Jardim-Perassi, Bruna Victorasso; Calvinho, Guilherme Berto; Facchini, Mariana Castilho; Viloria-Petit, Alicia M; de Campos Zuccari, Debora Aparecida Pires

2017-08-15

Mammary tumorigenesis can be modulated by melatonin, which has oncostatic action mediated by multiple mechanisms, including the inhibition of the activity of transcription factors such as NF-κB and modulation of interleukins (ILs) expression. IL-25 is an active cytokine that induces apoptosis in tumor cells due to differential expression of its receptor (IL-17RB). IL-17B competes with IL-25 for binding to IL-17RB in tumor cells, promoting tumorigenesis. This study purpose is to address the possibility of engaging IL-25/IL-17RB signaling to enhance the effect of melatonin on breast cancer cells. Breast cancer cell lines were cultured monolayers and 3D structures and treated with melatonin, IL-25, siIL-17B, each alone or in combination. Cell viability, gene and protein expression of caspase-3, cleaved caspase-3 and VEGF-A were performed by qPCR and immunofluorescence. In addition, an apoptosis membrane array was performed in metastatic cells. Treatments with melatonin and IL-25 significantly reduced tumor cells viability at 1mM and 1ng/mL, respectively, but did not alter cell viability of a non-tumorigenic epithelial cell line (MCF-10A). All treatments, alone and combined, significantly increased cleaved caspase-3 in tumor cells grown as monolayers and 3D structures (pmelatonin treatment. All treatments reduced VEGF-A protein expression in tumor cells (pmelatonin and IL-25-driven signaling in breast cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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. 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. 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 detailed investigations.

Intensive cytokine induction in pandemic H1N1 influenza virus infection accompanied by robust production of IL-10 and IL-6.

Directory of Open Access Journals (Sweden)

Xuelian Yu

Full Text Available 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

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

DEFF Research Database (Denmark)

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

2013-01-01

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

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.

Raised IL-6 Levels

African Journals Online (AJOL)

user

Cardiovascular Associated Complications in HIV. Positive Zambians before ... compare plasma levels of IL-6 in HIV positive and. HIV negative .... cancer. Results from this study showed that IL-6 levels in. HIV positive ART naive individuals were significantly higher than in the HIV positive individuals on ART. Our findings ...

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

IL-21: an executor of B cell fate.

Science.gov (United States)

Konforte, Danijela; Simard, Nathalie; Paige, Christopher J

2009-02-15

IL-21 is a type I cytokine that shares the common receptor gamma-chain with IL-2, IL-4, IL-7, IL-9, and IL-15. B cells are one of the lymphoid cell types whose development and function are regulated by IL-21. Depending on the interplay with costimulatory signals and on the developmental stage of a B cell, IL-21 can induce proliferation, differentiation into Ig-producing plasma cells, or apoptosis in both mice and humans. Alone and in combination with Th cell-derived cytokines IL-21 can regulate class switch recombination to IgG, IgA, or IgE isotypes, indicating its important role in shaping the effector function of B cells. This review highlights the role of IL-21 in B cell development, function, and disease and provides some perspectives on the future studies in this area.

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.

Effect of long-term inhalation of glucocorticoids on the level of leptin, IL-13 and IL-2 in bronchial asthmatic children

International Nuclear Information System (INIS)

Pan Jiongwei

2011-01-01

Objective: To determine the effect of long-term inhalation of glucocorticoids on the level of leptin, IL-13, and IL-2 in bronchial asthmatic patient. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum IL-13 and IL-2 level in 60 healthy persons (normal control group) and 70 bronchial asthma patients untreated and 3, 6, 12 months post-treatment, meanwhile leptin was determined by radio immunoassay. Results: The serum levels of leptin, Il-13, and IL-2 in were significantly increased in patient with bronchial asthma compared with that in the normal control group. The serum levels of leptin, IL-13, and IL-2 in children with asthma were decreased gradually after inhaling glucocorticoids for 3 months (P<0.05). The treatment of inhaled glucocorticoids for 6 and 12 months can attenuate the elevation of leptin, IL-13, and IL-2 compared with that before the treatment. Conclusion: Long-term inhaled glucocorticoid is an important means for asthma, and the effects are related to the decrease of level of leptin, IL-13, and IL-2. (authors)

IL-1Ra: its role in rheumatoid arthritis

Directory of Open Access Journals (Sweden)

M. Cutolo

2011-09-01

Full Text Available Interleukin-1 (IL-1 is one of the pivotal cytokines in initiating and driving the processes of rheumatoid arthritis (RA, and the body’s natural response, IL-1 receptor antagonist (IL-1Ra, has been shown conclusively to block its effects. IL-1 mediate several clinical symptoms of the inflammatory reaction (i.e. fever, pain, sleep disturbances. IL-1 is considered a key mediator in RA joint damage because of its greater capacity (greater than TNF of increasing matrix degradation by inducing the production of MMPs and PGE2 in synovial cells, as well by its role as mediator of bone and cartilage destruction. In addition, IL-1 decreases the repair process by suppressing matrix synthesis and shows a strong synergism with TNF in inducing many inflammatory genes at both local and systemic level. The induced endogenous production of IL-1Ra, in presence of the RA synovitis, is too low to contrast the high affinity of IL-1 for the cell receptors. Therefore, IL-1Ra presence should result in very effective prevention of IL-1 signal transduction particularly in the inflammatory site. In laboratory and animal studies inhibition of IL-1 by either antibodies to IL-1 or IL-1Ra proved beneficial to the outcome. IL-1Ra is a member of the IL-1 superfamily. The effects of different DMARDs on IL-1Ra levels in RA patients support the important role that selected anticytokine treatments might exert in the pathophysiology of the disease. However, since anti TNFα therapy it is not effective in all RA patients, nor does it fully control the arthritic process in affected joints of good responders and complete TNF suppression should be avoided, the combined treatment with intermediate doses of TNF and IL-1 blockers, reaching synergistic suppression of arthritis, seems warranted in RA.

Influence of IL1B, IL6 and IL10 gene variants and plasma fatty acid interaction on metabolic syndrome risk in a cross-sectional population-based study.

Science.gov (United States)

Maintinguer Norde, Marina; Oki, Erica; Ferreira Carioca, Antonio Augusto; Teixeira Damasceno, Nágila Raquel; Fisberg, Regina Mara; Lobo Marchioni, Dirce Maria; Rogero, Marcelo Macedo

2018-04-01

Metabolic syndrome (MetS) is a cluster of interrelated risk factors for type 2 diabetes mellitus, and cardiovascular disease, with underlying inflammatory pathophysiology. Genetic variations and diet are well-known risk factor for MetS, but the interaction between these two factors is less explored. The aim of the study was to evaluate the influence of interaction between SNP of inflammatory genes (encoding interleukin (IL)-6, IL-1β and IL-10) and plasma fatty acids on the odds of MetS, in a population-based cross-sectional study. Among participants of the Health Survey - São Paulo, 301 adults (19-59 y) from whom a blood sample was collected were included. Individuals with and without MetS were compared according to their plasma inflammatory biomarkers, fatty acid profile, and genotype frequency of the IL1B (rs16944, rs1143623, rs1143627, rs1143634 and rs1143643), IL6 (rs1800795, rs1800796 and rs1800797) and IL10 (rs1554286, rs1800871, rs1800872, rs1800890 and rs3024490) genes SNP. The influence of gene-fatty acids interaction on MetS risk was investigated. IL6 gene SNP rs1800795 G allele was associated with higher odds for MetS (OR = 1.88; p = 0.017). Gene-fatty acid interaction was found between the IL1B gene SNP rs116944 and stearic acid (p inter = 0.043), and between rs1143634 and EPA (p inter = 0.017). For the IL10 gene SNP rs1800896, an interaction was found for arachidonic acid (p inter = 0.007) and estimated D5D activity (p inter = 0.019). The IL6 gene SNP rs1800795 G allele is associated with increased odds for MetS. Plasma fatty acid profile interacts with the IL1B and IL10 gene variants to modulate the odds for MetS. This and other interactions of risk factors can account for the unexplained heritability of MetS, and their elucidation can lead to new strategies for genome-customized prevention of MetS. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Changes of serum IL-1 and sIL-2R levels after intravenous photo-coagulation in patients with varicose greater saphenous vein

International Nuclear Information System (INIS)

Han Li'na; Gu Ying; Liu Fanguang

2004-01-01

Objective: To determine the changes of serum interleukin 2 (IL-2) and soluble interleukin 2 receptor (sIL-2R) levels in patients with varicose greater saphenous vein after intravenous photocoagulation. Methods: Fifty patients with varicose greater saphenous vein were divided into two groups (mild and severe) according to their clinical symptoms. Serum IL-2 and sIL-2R levels were determined with RIA and ELISA respectively in these patients and 30 controls. Results: Serum levels of IL-2 and sIL-2R in patients of the mild group were about the same as those in the controls. In patients of the severe group, levels of IL-2 decreased and levels of sIL-2R increased significantly. After photocoagulation, the IL-2 levels dropped at first but gradually rose; the reverse was true for the sIL-2R levels. The final levels of IL-2 and sIL-2R approached those before treatment in the mild group. In the severe group, the final IL-2 levels were higher and sIL-2R levels lower than those before photocoagulation. Conclusion: Determination of serum IL-2 and sIL-2R levels revealed information about the immune status of the patients and could be applied for judgement of the treatment effect

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

Association of IL1A and IL1B loci with primary open angle glaucoma

Directory of Open Access Journals (Sweden)

Mukhopadhyay Indranil

2010-06-01

Full Text Available Abstract Background Recent studies suggest that glaucoma is a neurodegenerative disease in which secondary degenerative losses occur after primary insult by raised Intraocular pressure (IOP or by other associated factors. It has been reported that polymorphisms in the IL1A and IL1B genes are associated with Primary Open Angle Glaucoma (POAG. The purpose of our study was to investigate the role of these polymorphisms in eastern Indian POAG patients. Methods The study involved 315 unrelated POAG patients, consisting of 116 High Tension Glaucoma (HTG patients with intra ocular pressure (IOP > 21 mmHg and 199 non-HTG patients (presenting IOP IL1A (-889C/T; rs1800587, IL1B (-511C/T; rs16944 and IL1B (3953C/T; rs1143634. Haplotype frequency was determined by Haploview 4.1 software. The association of individual SNPs and major haplotypes was evaluated using chi-square statistics. The p-value was corrected for multiple tests by Bonferroni method. Results No significant difference was observed in the allele and genotype frequencies for IL1A and IL1B SNPs between total pool of POAG patients and controls. However, on segregating the patient pool to HTG and non-HTG groups, weak association was observed for IL1A polymorphism (-889C/T where -889C allele was found to portray risk (OR = 1.380; 95% CI = 1.041-1.830; p = 0.025 for non-HTG patients. Similarly, 3953T allele of IL1B polymorphism (+3953C/T was observed to confer risk to HTG group (OR = 1.561; 95% CI = 1.022-2.385; p = 0.039. On haplotype analysis it was observed that TTC was significantly underrepresented in non-HTG patients (OR = 0.538; 95% CI = 0.356- 0.815; p = 0.003 while TCT haplotype was overrepresented in HTG patients (OR = 1.784; 95% CI = 1.084- 2.937; p = 0.022 compared to control pool. However, after correction for multiple tests by Bonferroni method, an association of only TTC haplotype with non-HTG cases sustained (pcorrected = 0.015 and expected to confer protection. Conclusion The study

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)

Association study of IL10, IL1beta, and IL1RN and schizophrenia using tag SNPs from a comprehensive database: suggestive association with rs16944 at IL1beta.

Science.gov (United States)

Shirts, Brian H; Wood, Joel; Yolken, Robert H; Nimgaonkar, Vishwajit L

2006-12-01

Genetic association studies of several candidate cytokine genes have been motivated by evidence of immune dysfunction among patients with schizophrenia. Intriguing but inconsistent associations have been reported with polymorphisms of three positional candidate genes, namely IL1beta, IL1RN, and IL10. We used comprehensive sequencing data from the Seattle SNPs database to select tag SNPs that represent all common polymorphisms in the Caucasian population at these loci. Associations with 28 tag SNPs were evaluated in 478 cases and 501 unscreened control individuals, while accounting for population sub-structure using the genomic control method. The samples were also stratified by gender, diagnostic category, and exposure to infectious agents. Significant association was not detected after correcting for multiple comparisons. However, meta-analysis of our data combined with previously published association studies of rs16944 (IL1beta -511) suggests that the C allele confers modest risk for schizophrenia among individuals reporting Caucasian ancestry, but not Asians (Caucasians, n=819 cases, 1292 controls; p=0.0013, OR=1.24, 95% CI 1.09, 1.41).

IL-2 induction of IL-1 beta mRNA expression in monocytes. Regulation by agents that block second messenger pathways

DEFF Research Database (Denmark)

Kovacs, E J; Brock, B; Varesio, L

1989-01-01

We have previously shown that in mixed cultures of PBL incubation with human rIL-2 induces the rapid expression of IL-1 alpha and IL-1 beta mRNA. Because studies have demonstrated that IL-2R can be expressed on the surface of human peripheral blood monocytes, we chose to investigate whether IL-1 ...

Higher proliferation of peritumoral endothelial cells to IL-6/sIL-6R than tumoral endothelial cells in hepatocellular carcinoma

International Nuclear Information System (INIS)

Zhuang, Peng-Yuan; Wang, Jian-Dong; Tang, Zhao-Hui; Zhou, Xue-Ping; Quan, Zhi-Wei; Liu, Ying-Bin; Shen, Jun

2015-01-01

This study aimed to explore the responses to the interleukin-6 (IL-6)/soluble interleukin-6 receptor (sIL-6R) complex in peritumoral endothelial cells (PECs) and tumor endothelial cells (TECs), as well as determine the signaling pathways in the angiogenesis of hepatocellular carcinoma (HCC). The expression of IL-6, IL-6R, gp130, CD68, HIF-1α, and microvessel density (MVD) were assessed with an orthotopic xenograft model in nude mice. ECs were incubated under hypoxic conditions to detect IL-6 and gp130. The proliferation of PECs and TECs in the presence of IL-6 and sIL-6R, as well as the expression of gp130, JAK2/STAT3, PI3K/AKT in endothelial cells were measured. Peritumoral IL-6, IL-6R, gp130, CD68, and HIF-1α expression, as well as MVD, gradually increased during tumor growth. Hypoxia could directly induce IL-6 expression, but not gp130 in PECs. The co-culture of IL-6/sIL-6R induced much higher PEC proliferation and gp130 expression, as well as the elevated phosphorylation of JAK2 and STAT3, however not the phosphorylation of PI3K and AKT. PECs exhibited higher proliferation in response to IL-6/sIL-6R co-treatment compared with TECs in HCC via the up-regulation of gp130 /JAK2/STAT3. PEC and its associated peritumoral angiogenesis microenvironment may be a potential novel target for anti-angiogenic treatment. The online version of this article (doi:10.1186/s12885-015-1763-2) contains supplementary material, which is available to authorized users

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.

Disintegration-Rate Determination by 4 {pi} Counting; Determination du taux de desintegrations par comptage 4 {pi}; Opredelenie skorosti raspada pri pomotsi 4 {pi} schetchikov; Determinacion de la velocidad de desintegracion por recuento 4 {pi}

Energy Technology Data Exchange (ETDEWEB)

Pate, Brian D [Chemistry Department, Washington University, St. Louis, MO (United States)

1960-06-15

The history of the development of the 4 {pi} counting method is reviewed. The unique properties of the 4 {pi} counter system are described and the criteria are specified which place disintegration rate measurements, made with the system, on an absolute basis. The types of radioactive decay process to which the method is applicable are outlined, together with the various errors to which a given measurement is liable. Departure of response probability from unity, absorption of radiation in the source-mounting system, and source self-absorption are discussed in detail. (author) [French] L'auteur fait l'historique des progres de la methode de comptage 4 {pi}. Il decrit les proprietes remarquables du dispositif de comptage 4 {pi} et precise les conditions dans lesquelles les mesures du taux de desintegration se font avec ce dispositif sur une base absolue. Il donne un apercu des types de processus de desintegration radioactive, ainsi que de diverses erreurs auxquelles est sujette une mesure donnee. Il examine en detail le cas ou la probabilite de reponse s'ecarte de l'unite, l'absorption des rayonnements dans le support de la source et l'autoabsorption de la source. (author) [Spanish] En la memoria el autor expone el desarrollo del metodo de recuento 4 {pi}. Describe las caracteristicas particulares de este metodo y explica las razones por las que las mediciones de la velocidad de desintegracion efectuadas segun ese procedimiento tienen un caracter absoluto. Se indican, asimismo, los tipos de procesos de desintegracion radiactiva a los que se puede aplicar el metodo, asi como los diferentes defectos de que puede adolecer una medicion determinada. Tambien se estudia detenidamente el caso en que la probabilidad de respuesta no es igual a la unidad, la absorcion de radiaciones en el soporte de la fuente y la autoabsorcion de la misma. (author) [Russian] Daetsya obzor istorii razvitiya metoda scheta s pomoshch'yu 4 {pi} schetchikov. Privoditsya opisanie unikal'nykh svojstv

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.

Membrane-bound IL-12 and IL-23 serve as potent mucosal adjuvants when co-presented on whole inactivated influenza vaccines.

Science.gov (United States)

Khan, Tila; Heffron, Connie L; High, Kevin P; Roberts, Paul C

2014-05-03

Potent and safe adjuvants are needed to improve the efficacy of parenteral and mucosal vaccines. Cytokines, chemokines and growth factors have all proven to be effective immunomodulatory adjuvants when administered with a variety of antigens. We have previously evaluated the efficacy of membrane-anchored interleukins (IL) such as IL-2 and IL-4 co-presented as Cytokine-bearing Influenza Vaccines (CYT-IVACs) using a mouse model of influenza challenge. Here, we describe studies evaluating the parenteral and mucosal adjuvanticity of membrane-bound IL-12 and IL-23 CYT-IVACs in young adult mice. Mucosal immunization using IL-12 and IL-23 bearing whole influenza virus vaccine (WIV) was more effective at eliciting virus-specific nasal IgA and reducing viral lung burden following challenge compared to control WIV vaccinated animals. Both IL-12 and IL-23 bearing WIV elicited the highest anti-viral IgA levels in serum and nasal washes. This study highlights for the first time the mucosal adjuvant potential of IL-12 and IL-23 CYT-IVAC formulations in eliciting mucosal immune responses and reducing viral lung burden. The co-presentation of immunomodulators in direct context with viral antigen in whole inactivated viral vaccines may provide a means to significantly lower the dose of vaccine required for protection.

Dynamic monitoring of serum IFN-γ, IL-2, and IL-6 contents in patients with Graves' disease

International Nuclear Information System (INIS)

Zou Jianwen; Li Weiguo

2006-01-01

Objective: To investigate the possible role of cytokines (IFN-γ, IL-2, IL-6) in the pathogenesis of Graves' disease. Methods: Serum FT 3 , FT 4 , TSH (with CLIA), IL-2, IL-6 (with RIA) and IFN-γ (with ELISA) contents were measured in the following subjects: (1) 42 patients with Graves' disease before any treatment, (2) 40 patients in remission after successful treatment with antithyroid drugs (ATD), (3) 25 patients in relapse (around 6 months after cessation of two years' ATD treatment, (4) 40 controls. Results: The serum IFN-γ and IL-6 contents in the patients before treatment and patients in relapse were significantly higher than those in the controls (P 3 , FT 4 levels while the serum IL-2 contents were linearly negatively correlated with FT 3 , FT 4 levels before treatment. Conclusion: Contents of these cytokines fluctuated dynamically along with the status of Graves' disease and might be related to the pathogenesis in some way. (authors)

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.

IL-6 and mouse oocyte spindle.

Directory of Open Access Journals (Sweden)

Jashoman Banerjee

Full Text Available Interleukin 6 (IL-6 is considered a major indicator of the acute-phase inflammatory response. Endometriosis and pelvic inflammation, diseases that manifest elevated levels of IL-6, are commonly associated with higher infertility. However, the mechanistic link between elevated levels of IL-6 and poor oocyte quality is still unclear. In this work, we explored the direct role of this cytokine as a possible mediator for impaired oocyte spindle and chromosomal structure, which is a critical hurdle in the management of infertility. Metaphase-II mouse oocytes were exposed to recombinant mouse IL-6 (50, 100 and 200 ng/mL for 30 minutes and subjected to indirect immunofluorescent staining to identify alterations in the microtubule and chromosomal alignment compared to untreated controls. The deterioration in microtubule and chromosomal alignment were evaluated utilizing both fluorescence and confocal microscopy, and were quantitated with a previously reported scoring system. Our results showed that IL-6 caused a dose-dependent deterioration in microtubule and chromosomal alignment in the treated oocytes as compared to the untreated group. Indeed, IL-6 at a concentration as low as 50 ng/mL caused deterioration in the spindle structure in 60% of the oocytes, which increased significantly (P<0.0001 as IL-6 concentration was increased. In conclusion, elevated levels of IL-6 associated with endometriosis and pelvic inflammation may reduce the fertilizing capacity of human oocyte through a mechanism that involves impairment of the microtubule and chromosomal structure.

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)

Autocrine IL-6 mediates pituitary tumor senescence

Science.gov (United States)

Fuertes, Mariana; Ajler, Pablo; Carrizo, Guillermo; Cervio, Andrés; Sevlever, Gustavo; Stalla, Günter K.; Arzt, Eduardo

2017-01-01

Cellular senescence is a stable proliferative arrest state. Pituitary adenomas are frequent and mostly benign, but the mechanism for this remains unknown. IL-6 is involved in pituitary tumor progression and is produced by the tumoral cells. In a cell autonomous fashion, IL-6 participates in oncogene-induced senescence in transduced human melanocytes. Here we prove that autocrine IL-6 participates in pituitary tumor senescence. Endogenous IL-6 inhibition in somatotroph MtT/S shRNA stable clones results in decreased SA-β-gal activity and p16INK4a but increased pRb, proliferation and invasion. Nude mice injected with IL-6 silenced clones develop tumors contrary to MtT/S wild type that do not, demonstrating that clones that escape senescence are capable of becoming tumorigenic. When endogenous IL-6 is silenced, cell cultures derived from positive SA-β-gal human tumor samples decrease the expression of the senescence marker. Our results establish that IL-6 contributes to maintain senescence by its autocrine action, providing a natural model of IL-6 mediated benign adenoma senescence. PMID:27902467

Contributo di dati di gravità nella valutazione del vulcanismo CAMP in Africa Nord-Occidentale

OpenAIRE

Fabbri, Julius

2015-01-01

2013/2014 La domanda alla base di questa ricerca è stata se il metodo della gravimetria satellitare possa essere utilizzato per seguire le unità geologiche anche in luoghi difficilmente accessibili. L’obiettivo di questa ricerca è di verificare se le missioni satellitari di nuova generazione permettano di identificare la più grande delle province ignee della Terra (Bertrand et al., 2013), nota come CAMP (Central Atlantic Magmatic Province) in Africa nord-occidentale. Oltre alle motivazioni...

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

Science.gov (United States)

Raviprakash, Nune; Manna, Sunil Kumar

2014-01-01

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

IL10-Deficiency in CD4+ T Cells Exacerbates the IFNγ and IL17 Response During Bacteria Induced Colitis

Directory of Open Access Journals (Sweden)

Virginia Seiffart

2015-07-01

Full Text Available Background/Aims: IL10 is a key inhibitor of effector T cell activation and a mediator of intestinal homeostasis. In addition, IL10 has emerged as a key immunoregulator during infection with various pathogens, ameliorating the excessive T-cell responses that are responsible for much of the immunopathology associated with the infection. Because IL10 plays an important role in both intestinal homeostasis and infection, we studied the function of IL10 in infection-associated intestinal inflammation. Methods: Wildtype mice and mice deficient in CD4+ T cell-derived or regulatory T cells-derived IL10 were infected with the enteric pathogen Citrobacter (C. rodentium and analyzed for the specific immune response and pathogloy in the colon. Results: We found that IL10 expression is upregulated in colonic tissue after infection with C. rodentium, especially in CD4+ T cells, macrophages and dendritic cells. Whereas the deletion of IL10 in regulatory T cells had no effect on C. rodentium induced colitis, infection of mice deficient in CD4+ T cell-derived IL10 exhibited faster clearance of the bacterial burden but worse colitis, crypt hyperplasia, and pathology than did WT mice. In addition, the depletion of CD4+ T cell-derived IL10 in infected animals was accompanied by an accelerated IFNγ and IL17 response in the colon. Conclusion: Thus, we conclude that CD4+ T cell-derived IL10 is strongly involved in the control of C. rodentium-induced colitis. Interference with this network could have implications for the treatment of infection-associated intestinal inflammation.

[Brd3 promotes IL-6 production via enhancing acetylase CBP recruitment and histone 3 acetylation within IL6 promoter].

Science.gov (United States)

Ren, Wenhui; Sun, Donghao; Wang, Chunmei; Li, Nan

2016-10-01

Objective To investigate the role of bromodomain containing 3 (Brd3) in LPS-triggered interleukin-6 (IL-6) production in macrophages and the underlying mechanism. Methods CRISPR-Cas9 technology was used to screen an RAW264.7 cell line with Brd3 knockout (Brd3 -/- ). The Brd3 -/- cells were used as an experimental group, and the parential cells expressing wide-type Brd3 as a control group. The IL-6 level in cell culture supernatant was detected by ELISA after 100 ng/mL LPS challenging. Effect of Brd3 knockout on the expression and activation of signal pathways involved in IL-6 expression, including the NF-κB and mitogen-activated protein kinase (MAPK) pathways were examined by Western blot analysis. Chromatin immunoprecipitation (ChIP) assay was used to evaluate the recruitment of acetylase CREB-binding protein (CBP) to IL6 gene promoter and the acetylation level of histone 3 within IL6 gene promoter. Results LPS treatment significantly downregulated Brd3 expression in mouse peritoneal macrophages. LPS-induced production of IL-6 was significantly inhibited in Brd3 -/- macrophages. The expressions and activation of signal molecules within NF-κB and MAPK pathways were barely affected. Brd3 knockout significantly decreased the recruitment of acetylase CBP to IL6 gene promoter, and the acetylation level of histone3 within IL6 gene promoter was also repressed. Conclusion Brd3 promotes LPS-triggered IL-6 production via promoting the recruitment of CBP to IL6 promoter and enhancing the acetylation level of histone 3 within IL6 promoter.

RNA-Seq Analysis of IL-1B and IL-36 Responses in Epidermal Keratinocytes Identifies a Shared MyD88-Dependent Gene Signature.

Science.gov (United States)

Swindell, William R; Beamer, Maria A; Sarkar, Mrinal K; Loftus, Shannon; Fullmer, Joseph; Xing, Xianying; Ward, Nicole L; Tsoi, Lam C; Kahlenberg, Michelle J; Liang, Yun; Gudjonsson, Johann E

2018-01-01

IL-36 cytokines have recently emerged as mediators of inflammation in autoimmune conditions including psoriasis vulgaris (PsV) and generalized pustular psoriasis (GPP). This study used RNA-seq to profile the transcriptome of primary epidermal keratinocytes (KCs) treated with IL-1B, IL-36A, IL-36B, or IL-36G. We identified some early IL-1B-specific responses (8 h posttreatment), but nearly all late IL-1B responses were replicated by IL-36 cytokines (24 h posttreatment). Type I and II interferon genes exhibited time-dependent response patterns, with early induction (8 h) followed by no response or repression (24 h). Altogether, we identified 225 differentially expressed genes (DEGs) with shared responses to all 4 cytokines at both time points (8 and 24 h). These involved upregulation of ligands ( IL1A, IL1B , and IL36G ) and activating proteases ( CTSS ) but also upregulation of inhibitors such as IL1RN and IL36RN . Shared IL-1B/IL-36 DEGs overlapped significantly with genes altered in PsV and GPP skin lesions, as well as genes near GWAS loci linked to autoimmune and autoinflammatory diseases (e.g., PsV, psoriatic arthritis, inflammatory bowel disease, and primary biliary cholangitis). Inactivation of MyD88 adapter protein using CRISPR/Cas9 completely abolished expression responses of such DEGs to IL-1B and IL-36G stimulation. These results provide a global view of IL-1B and IL-36 expression responses in epidermal KCs with fine-scale characterization of time-dependent and cytokine-specific response patterns. Our findings support an important role for IL-1B and IL-36 in autoimmune or autoinflammatory conditions and show that MyD88 adaptor protein mediates shared IL-1B/IL-36 responses.

Polycyclic aromatic hydrocarbons reciprocally regulate IL-22 and IL-17 cytokines in peripheral blood mononuclear cells from both healthy and asthmatic subjects.

Directory of Open Access Journals (Sweden)

Coline Plé

Full Text Available Pollution, including polycyclic aromatic hydrocarbons (PAH, may contribute to increased prevalence of asthma. PAH can bind to the Aryl hydrocarbon Receptor (AhR, a transcription factor involved in Th17/Th22 type polarization. These cells produce IL17A and IL-22, which allow neutrophil recruitment, airway smooth muscle proliferation and tissue repair and remodeling. Increased IL-17 and IL-22 productions have been associated with asthma. We hypothesized that PAH might affect, through their effects on AhR, IL-17 and IL-22 production in allergic asthmatics. Activated peripheral blood mononuclear cells (PBMCs from 16 nonallergic nonasthmatic (NA and 16 intermittent allergic asthmatic (AA subjects were incubated with PAH, and IL-17 and IL-22 productions were assessed. At baseline, activated PBMCs from AA exhibited an increased IL-17/IL-22 profile compared with NA subjects. Diesel exhaust particle (DEP-PAH and Benzo[a]Pyrene (B[a]P stimulation further increased IL-22 but decreased IL-17A production in both groups. The PAH-induced IL-22 levels in asthmatic patients were significantly higher than in healthy subjects. Among PBMCs, PAH-induced IL-22 expression originated principally from single IL-22- but not from IL-17- expressing CD4 T cells. The Th17 transcription factors RORA and RORC were down regulated, whereas AhR target gene CYP1A1 was upregulated. IL-22 induction by DEP-PAH was mainly dependent upon AhR whereas IL-22 induction by B[a]P was dependent upon activation of PI3K and JNK. Altogether, these data suggest that DEP-PAH and B[a]P may contribute to increased IL22 production in both healthy and asthmatic subjects through mechanisms involving both AhR -dependent and -independent pathways.

Test of numerical methods for the integration of kinetic equations in tropospheric chemistry; Confronto di metodi numerici per l'integrazione di sistemi di equazioni differenziali ordinarie di tipo STIFF inserite nel modello fotochimico Calgrid

Energy Technology Data Exchange (ETDEWEB)

Lorenzini, R.; Passoni, L. [ENEA, Centro Ricerche Ezio Clementel, Bologna (Italy). Dipt. Ambiente

1999-07-01

The integration of ordinary differential equations systems (ODEs) is of significant concern to tropospheric and stratospheric chemistry modelers. The solution of the ODEs requires a large computational effort because of their stiff nature; in a three-dimensional photochemical model the solution of the ODEs required at least 70% of the total CPU time. Several numerical integration techniques exist which attempt to provide accurate and computationally efficient solutions. In this work it is presented a comparison of some of the techniques in terms of solution accuracy and required computational time. It has been compared the Hybrid Solver (Young and Boris, 1977), the Quasi Steady-State Approximation method (Hesstvedt et al., 1978) and the Chemical Solver for Ordinary Differential Equations (Aro, 1996), by using the CALGRID photochemical model. The accuracy is evaluated by comparing the results of every method with the solutions obtained by the Livermore Solver for Ordinary Differential Equations (Hindmarsh, 1980). The comparison has been made varing the parameters of the error tolerances, and taking into account the trade-off between solution accuracy and computational efficiency. [Italian] L'integrazione di sistemi di equazioni differenziali ordinarie (ODEs), e' un problema significativo per i modellisti della chimica troposferica e stratosferica. A causa della loro natura stiff la soluzione degli ODEs richiese un notevole sforzo computazionale; in un modello fotochimico tridimensionale la soluzione degli ODEs richiede almeno il 70% del tempo totale di CPU. Esistono diverse tecniche di integrazione numerica che possono fornire soluzioni accurate e computazionalmente efficienti: in questo lavoro presentiamo un confronto fra alcune tecniche in termini di accuratezza della soluzione e tempo computazionale richiesto. Si sono confrontati il Solver Ibrido (Young and Boris, 1977), il metodo Quasi Steady-State Approximation (Hesstvedt et al., 1978) ed il Chemical

Central Role of IL-23 and IL-17 Producing Eosinophils as Immunomodulatory Effector Cells in Acute Pulmonary Aspergillosis and Allergic Asthma.

Science.gov (United States)

Guerra, Evelyn Santos; Lee, Chrono K; Specht, Charles A; Yadav, Bhawna; Huang, Haibin; Akalin, Ali; Huh, Jun R; Mueller, Christian; Levitz, Stuart M

2017-01-01

Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A. fumigatus conidia in vivo. Eosinopenic mice had higher mortality rates, decreased recruitment of inflammatory monocytes, and decreased expansion of lung macrophages after challenge with conidia. All of these functions underscore a potential protective role for eosinophils in acute aspergillosis. Given the postulated role for IL-17 in asthma pathogenesis, we assessed whether eosinophils could act as sources of IL-23 and IL-17 in models where mice were sensitized to either A. fumigatus antigens or ovalbumin (OVA). We found IL-23p19+ IL-17AF+ eosinophils in both allergic models. Moreover, close to 95% of IL-23p19+ cells and >90% of IL-17AF+ cells were identified as eosinophils. These data establish a new paradigm in acute and allergic aspergillosis whereby eosinophils act not only as effector cells but also as immunomodulatory cells driving the IL-23/IL-17 axis and contributing to inflammatory cell recruitment.

Expression of TNF, IL-17A, IL-4 and IL-10 cytokines in irradiated peripheral blood mononuclear cells 'In vitro'; Expressão das citocinas TNF, IL-17A, IL-4 e IL-10 em células mononucleares do sangue periférico irradiadas 'in vitro'

Energy Technology Data Exchange (ETDEWEB)

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, E-mail: maribrayner@yahoo.com.br [Universidade Federal de Pernambuco (GERAR/DEN/UFPE), Recife, PE (Brazil). Grupo de Estudos em Radioproteção e Radioecologia; Dantas, Samuel César [Instituto de Medicina Integrada Prof. Antônio Figueira (IMIP), PE (Brazil); Veras, Robson Cavalcante; Medeiros, Isac Almeida de [Universidade Federal da Paraiba (DCF/UFPB), PB (Brazil). Departamento de Ciências Farmacêuticas

2017-07-01

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)

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

International Nuclear Information System (INIS)

Wang Tongwu

2009-01-01

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

Effects of flurbiprofen axetil on postoperative serum IL-2 and IL-6 levels in patients with colorectal cancer.

Science.gov (United States)

Jiang, W W; Wang, Q H; Peng, P; Liao, Y J; Duan, H X; Xu, M; Li, Y; Zhang, P B

2015-12-09

We explored the effects of flurbiprofen axetil on interleukin (IL)-2 and IL-6 levels in postoperative patients with colorectal cancer. A total of 120 patients (American Society of Anesthesiologists I and II) scheduled to undergo colorectal cancer surgery were randomly divided into 3 groups (N = 40 in each group): flurbiprofen axetil group (group F), morphine group (group M), and tramadol group (group T). Group M received 0.1 mg/kg morphine, group T received 1.5 mg/kg tramadol, and group F received 1.5 mg/kg flurbiprofen axetil. Patients in the 3 groups were administered treatments through intravenous injection 10 min before surgery. Serum IL-2 and IL-6 levels were detected. Postoperative adverse reactions were recorded, such as nausea, vomiting, and pruritus. The serum IL-6 level of the 3 groups increased 3 h after surgery. Compared with group M, IL-6 level was higher in group T and group F at 1 day after the surgery, and the differences between group M and the other groups were significant (P Flurbiprofen axetil promoted the secretion of IL-2 and inhibited IL-6; additionally, flurbiprofen axetil may have a lower incidence of adverse reactions compared to other treatments.

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.

Interleukin-6 (IL-6) receptor/IL-6 fusion protein (Hyper IL-6) effects on the neonatal mouse brain: possible role for IL-6 trans-signaling in brain development and functional neurobehavioral outcomes.

Science.gov (United States)

Brunssen, Susan H; Moy, Sheryl S; Toews, Arrel D; McPherson, Christopher A; Harry, G Jean

2013-01-01

Adverse neurodevelopmental outcomes are linked to perinatal production of inflammatory mediators, including interleukin 6 (IL-6). While a pivotal role for maternal elevation in IL-6 has been established in determining neurobehavioral outcomes in the offspring and considered the primary target mediating the fetal inflammatory response, questions remain as to the specific actions of IL-6 on the developing brain. CD-1 male mice received a subdural injection of the bioactive fusion protein, hyper IL-6 (HIL-6) on postnatal-day (PND)4 and assessed from preweaning until adulthood. Immunohistochemical evaluation of astrocytes and microglia and mRNA levels for pro-inflammatory cytokines and host response genes indicated no evidence of an acute neuroinflammatory injury response. HIL-6 accelerated motor development and increased reactivity to stimulation and number of entries in a light/dark chamber, decreased ability to learn to withhold a response in passive avoidance, and effected deficits in social novelty behavior. No changes were observed in motor activity, pre-pulse startle inhibition, or learning and memory in the Morris water maze or radial arm maze, as have been reported for models of more severe developmental neuroinflammation. In young animals, mRNA levels for MBP and PLP/DM20 decreased and less complexity of MBP processes in the cortex was evident by immunohistochemistry. The non-hydroxy cerebroside fraction of cerebral lipids was increased. These results provide evidence for selective effects of IL-6 signaling, particularly trans-signaling, in the developing brain in the absence of a general neuroinflammatory response. These data contribute to our further understanding of the multiple aspects of IL-6 signaling in the developing brain. Published by Elsevier Inc.

Estrogen and progesterone decrease let-7f microRNA expression and increase IL-23/IL-23 receptor signaling and IL-17A production in patients with severe asthma.

Science.gov (United States)

Newcomb, Dawn C; Cephus, Jacqueline Yvonne; Boswell, Madison G; Fahrenholz, John M; Langley, Emily W; Feldman, Amy S; Zhou, Weisong; Dulek, Daniel E; Goleniewska, Kasia; Woodward, Kimberly B; Sevin, Carla M; Hamilton, Robert G; Kolls, Jay K; Peebles, R Stokes

2015-10-01

Women have an increased prevalence of severe asthma compared with men. IL-17A is associated with severe asthma and requires IL-23 receptor (IL-23R) signaling, which is negatively regulated by let-7f microRNA. We sought to Determine the mechanism by which 17β-estradiol (E2) and progesterone (P4) increase IL-17A production. IL-17A production was determined by using flow cytometry in TH17 cells from women (n = 14) and men (n = 15) with severe asthma. Cytokine levels were measured by using ELISA, and IL-23R and let-7f expression was measured by using quantitative PCR in TH17-differentiated cells from healthy women (n = 13) and men (n = 14). In sham-operated or ovariectomized female mice, 17β-E2, P4, 17β-E2+P4, or vehicle pellets were administered for 3 weeks before ex vivo TH17 cell differentiation. Airway neutrophil infiltration and CXCL1 (KC) expression were also determined in ovalbumin (OVA)-challenged wild-type female recipient mice with an adoptive transfer of OVA-specific TH17 cells from female and male mice. In patients with severe asthma and healthy control subjects, IL-17A production was increased in TH17 cells from women compared with men. IL-23R expression was increased and let-7f expression was decreased in TH17-differentiated cells from women compared with men. In ovariectomized mice IL-17A and IL-23R expression was increased and Let-7f expression was decreased in TH17 cells from mice administered 17β-E2+P4 compared with those administered vehicle. Furthermore, transfer of female OVA-specific TH17 cells increased acute neutrophil infiltration in the lungs of OVA-challenged recipient mice compared with transfer of male OVA-specific TH17 cells. 17β-E2+P4 increased IL-17A production from TH17 cells, providing a potential mechanism for the increased prevalence of severe asthma in women compared with men. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Association of single nucleotide polymorphisms of IL23R and IL17 with ulcerative colitis risk in a Chinese Han population.

Directory of Open Access Journals (Sweden)

Pengli Yu

Full Text Available BACKGROUND: Previous studies implicated that IL23R and IL17 genes play an important role in autoimmune inflammation. Genome-wide association studies have also identified multiple single nucleotide polymorphisms (SNPs in the IL23R gene region associated with inflammatory bowel diseases. This study examined the association of IL23R and IL17A gene SNPs with ulcerative colitis susceptibility in a population in China. METHODOLOGY: A total of 270 ulcerative colitis and 268 healthy controls were recruited for the analyses of 23 SNPs in the IL23R and IL17A regions. Genomic DNA was extracted and analysis of these 23 SNPs using ligase detection reaction allelic (LDR technology. Genotype and allele associations were calculated using SPSS 13.0 software package. PRINCIPAL FINDINGS: Compared to the healthy controls, the variant alleles IL23R rs7530511, and rs11805303 showed a statistically significant difference for ulcerative colitis susceptibility (0.7% vs 3.3%, P = 0.002; 60.4% vs 53.2%, P = 0.0017, respectively. The linkage disequilibrium (LD patterns of these SNPs were measured and three LD blocks from the SNPs of IL23R and one block from those of IL17A were identified. A novel association with ulcerative colitis susceptibility occurred in haplotypes of IL23R (Block1 H3 P = 0.02; Block2 H2 P = 0.019; Block3 H4 P = 0.029 and IL17A (H4 P = 0.034. Pair-wise analyses showed an interaction between the risk haplotypes in IL23R and IL17A (P = 0.014. CONCLUSIONS: Our study demonstrated that rs7530511, and rs11805303 of IL23R were significantly associated with ulcerative colitis susceptibility in the Chinese population. The most noticeable finding was the linkage of IL23R and IL17A gene region to ulcerative colitis risk due to the gene-gene interaction.

IL-20 gene expression is induced by IL-1beta through mitogen-activated protein kinase and NF-kappaB-dependent mechanisms

DEFF Research Database (Denmark)

Otkjaer, Kristian; Kragballe, Knud; Johansen, Claus

2007-01-01

IL-20 is a novel member of the IL-10 cytokine family with pleiotropic effects. Current knowledge of what triggers and regulates IL-20 gene expression is sparse. The aim of this study was to investigate the regulation of IL-20 expression in cultured normal human keratinocytes. The expression of IL...

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

The interleukin (IL-1a precursor is biologically active and is likely a key alarmin in the IL-1 family of cytokines

Directory of Open Access Journals (Sweden)

Busun eKim

2013-11-01

Full Text Available Among the eleven members of the IL-1 family cytokines, the precursors of IL-1a, IL-1b, and IL-33 have relatively long N-terminal pro-sequences of approximately one hundred amino acid residues prior to the N-terminus of the mature forms. Compared to the mature forms secreted from the cell, 80-90% of the primary translation product is in the intracellular compartment in the precursor form. However, the precursors are readily released from cells during infections but also with non-infectious conditions such a hypoxia and trauma. In this setting, the precursors act rapidly as alarmins in the absence of a processing mechanism to remove the pro-sequence and generate a mature form. In the case of IL-1a, the release of the precursor activates adjacent cells via receptor-mediated signaling. However, there are no data comparing the specific activity of the IL-1a precursor to the mature form. In the present study, we compared the precursor and mature forms of recombinant human IL-1a, IL-1b and IL-33 proteins on the induction of cytokines from A549 cells as well as from human peripheral blood mononuclear cells (PBMC. Similar to the mature form, the IL-1a precursor was active in inducing IL 6 and TNFa, whereas the precursor forms of IL 1b and IL-33 were not active. On PBMC, precursor and mature IL-1a at 0.04 and 0.2 nano-mole were equally active in inducing IL-6. Given the fact that during necrotic cell death, the IL-1a precursor is released intact and triggers IL-1 receptors on tissue macrophages, these data identify the precursor form of IL-1a as a key player in sterile inflammation.

Transgenic Expression of IL15 Improves Antiglioma Activity of IL13Rα2-CAR T Cells but Results in Antigen Loss Variants.

Science.gov (United States)

Krenciute, Giedre; Prinzing, Brooke L; Yi, Zhongzhen; Wu, Meng-Fen; Liu, Hao; Dotti, Gianpietro; Balyasnikova, Irina V; Gottschalk, Stephen

2017-07-01

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and is virtually incurable with conventional therapies. Immunotherapy with T cells expressing GBM-specific chimeric antigen receptors (CAR) is an attractive approach to improve outcomes. Although CAR T cells targeting GBM antigens, such as IL13 receptor subunit α2 (IL13Rα2), HER2, and EGFR variant III (EGFRvIII), have had antitumor activity in preclinical models, early-phase clinical testing has demonstrated limited antiglioma activity. Transgenic expression of IL15 is an appealing strategy to enhance CAR T-cell effector function. We tested this approach in our IL13Rα2-positive glioma model in which limited IL13Rα2-CAR T-cell persistence results in recurrence of antigen-positive gliomas. T cells were genetically modified with retroviral vectors encoding IL13Rα2-CARs or IL15 (IL13Rα2-CAR.IL15 T cells). IL13Rα2-CAR.IL15 T cells recognized glioma cells in an antigen-dependent fashion, had greater proliferative capacity, and produced more cytokines after repeated stimulations in comparison with IL13Rα2-CAR T cells. No autonomous IL13Rα2-CAR.IL15 T-cell proliferation was observed; however, IL15 expression increased IL13Rα2-CAR T-cell viability in the absence of exogenous cytokines or antigen. In vivo , IL13Rα2-CAR.IL15 T cells persisted longer and had greater antiglioma activity than IL13Rα2-CAR T cells, resulting in a survival advantage. Gliomas recurring after 40 days after T-cell injection had downregulated IL13Rα2 expression, indicating that antigen loss variants occur in the setting of improved T-cell persistence. Thus, CAR T cells for GBM should not only be genetically modified to improve their proliferation and persistence, but also to target multiple antigens. Summary: Glioblastoma responds imperfectly to immunotherapy. Transgenic expression of IL15 in T cells expressing CARs improved their proliferative capacity, persistence, and cytokine production. The emergence of antigen

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

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)

Lo sfondo filosofico della fisica moderna

CERN Document Server

Heisenberg, Werner

1999-01-01

Questa raccolta di saggi, inedita nella sua composizione e nuova in senso assoluto per l'Italia, presenta il pensiero di Heisenberg in tutta la sua articolazione e completezza: le riflessioni filosofiche fondamentali, le originali considerazioni epistemologiche, il credo etico-religioso, la visione della realtà e le due memorie scientifiche nelle quali venne elaborata la meccanica delle matrici, che fissò la nascita della cosiddetta «seconda quantistica», determinando la crisi della fisica classica e delineando l'orizzonte di senso da cui è derivato il successivo principio di indeterminazione. Emerge un pensatore che ha fornito contributi essenziali sia alla storia del pensiero filosofico che a quello scientifico del Novecento, e che ha rappresentato un vero e proprio «punto di svolta» della cultura contemporanea. Un punto di svolta che ha condotto il «metodo» della scienza dal gretto riduzionismo dell'epoca classica a una sua più concreta elaborazione in senso storicistico e complesso. Werner Heise...

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.

IL-11, IL-1α, IL-6, and TNF-α are induced by solar radiation in vitro and may be involved in facial subcutaneous fat loss in vivo.

Science.gov (United States)

Li, Wen-Hwa; Pappas, Apostolos; Zhang, Li; Ruvolo, Eduardo; Cavender, Druie

2013-07-01

The loss of subcutaneous (sc) fat is associated with aging. Inflammatory cytokines, such as interleukin-1 α (IL-1α), interleukin-11 (IL-11) and tumor necrosis factor-α (TNF-α), are known to inhibit the differentiation of preadipocytes. This study investigated the potential role of inflammatory cytokines in solar-radiation-induced facial fat loss. Cultured fibroblasts, keratinocytes, and skin equivalents were exposed to various doses of radiation from a solar simulator. Inflammatory cytokines' mRNA production and protein secretion were examined by qRT-PCR and ELISA, respectively. In some experiments, epidermal-dermal equivalents were pretreated topically with a broad-spectrum sunscreen prior to solar simulated radiation (SSR). Human facial preadipocytes treated with recombinant IL-11 or with conditioned media from solar-irradiated equivalents were evaluated for the level of adipocyte differentiation by image analyses, Oil red O staining, and the expression of adipocyte differentiation markers. IL-11, IL-1α, IL-6, and TNF-α protein secretion were induced from epidermal-dermal equivalents by exposure to SSR. A sunscreen prevented SSR-induced inflammatory cytokines production from such equivalents. Exposure of facial preadipocytes to conditioned medium from solar-irradiated epidermal-dermal equivalents inhibited their differentiation into mature adipocytes. Consequently, conditioned medium from sunscreen-pretreated, solar-irradiated equivalents did not inhibit differentiation of preadipocytes. A cocktail of neutralizing antibodies to IL-11, IL-1α, IL-6 and TNF-α significantly reduced the SSR-induced inhibition of preadipocyte differentiation. These results support the hypothesis that SSR-induced inflammatory cytokine may be involved in the photoaging-induced loss of facial subcutaneous fat. Inhibition of this process, e.g. by sunscreens, might slow or prevent photoaging-induced changes in facial contouring. Copyright © 2013 Japanese Society for Investigative

Double-Sampling Method for Carrying Out Quality Control of a Fabrication Process; Methode du Double Echantillonnage pour le Controle de la Qualite d'un Procede de Fabrication; Metod dvukh obraztsov dlya osushchestvleniya kontrolya za kachestvom v protsesse izgotovleniya; Metodo de Muestreo Doble para el Control de Calidad de un Proceso de Fabricacion

Energy Technology Data Exchange (ETDEWEB)

Cerrolaza, J. A.; Lago, A.; Montojo, Rosa M. [Junta de Energia Nuclear, Madrid (Spain)

1966-02-15

taille des echantillons et le degre de controle sont determines en fonction des risques inherents a la premiere et a la deuxieme condition. Bien que cette methode soit applicable, elle est fort peu pratique quand il s'agit de controler des pieces de reacteurs, car les echantillons qu'elle exige sont de dimensions excessives. Le memoire expose une methode analogue a celle de Cave mais qui consiste a etablir un double echantillonnage dans lequel la taille moyenne de l'echantillon est beaucoup plus reduite. (author) [Spanish] La fabricacion de componentes que han de ser empleados en reactores nucleares presenta dos caracteristicas fundamentales que condicionan el proceso: la exigencia de una calidad muy elevada que limita a valores muy bajos el porcentaje de piezas defectuosas admisibles, y el coste muy alto de cada uno de los componentes. Estas dos condiciones obligan a que el control durante la fabricacion posea una curva de operacion con potencia muy elevada, y, por otra parte, a que el numero de piezas destruidas en cada inspeccion sea un pequeno como se pueda, siempre que se cumpla la condicion anterior. Los metodos usuales de control, basados en fijar el riesgo de primera especie, no son aplicables, ya que en general su eficacia no es suficiente. Cave ha desarrollado un metodo en que, tanto el tamano de las muestras como los limites de control, se fijan en funcion de los riesgos de primera y segunda especie. Este metodo, si bien es aplicable, resulta poco practico en el control de componentes para reactores, ya que se necesitan muestras de un tamano excesivamente grande. En el presente trabajo se desarrolla un metodo semejante al de Cave, pero en el que se establece un muestreo doble, con lo que el tamano medio de la muestra es mucho mas reducido. (author) [Russian] Pri izgotovlenii komponentov dlja ispol'zovanija v reaktorah reshajushhee znachenie imejut dva osnovnyh faktora, a imenno: neobhodimost' obespechit' ochen' vysokoe kachestvo, dopuskajushhee lish' ochen

Verifica di costruibilità in sicurezza con l’ausilio di strumenti grafici

Directory of Open Access Journals (Sweden)

Pietro Capone

2013-10-01

Full Text Available Il tema del presente contributo si inserisce a cavallo di due filoni di studi propri del Construction Management: la Sicurezza Cantieri e la Costruibilità. Per affrontare la questione si fa riferimento ad  un approccio che riconosce un ruolo chiave all’attività progettuale in generale ed, in particolare, alla evoluzione del Progetto Esecutivo in Costruttivo. Il metodo proposto consente, intervenendo sulla rappresentazione grafica degli elaborati progettuali, da una parte la valutazione specifica e dettagliata delle condizioni di sicurezza per la realizzazione dell’elemento in oggetto, e contestualmente di verificarne le condizioni di cantierabilità, in una fase precedente il cantiere e quindi in un momento in cui è ancora possibile intervenire, se del caso, con modifiche, più o meno significative sul progetto senza che esso ne risulti snaturato nella sua primitiva impostazione.

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.

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

Clinical significance of changes of serum IL-2, IL-6 and TNF-α levels after treatment in patients with periodontitis

International Nuclear Information System (INIS)

Wei Dong

2005-01-01

Objective: To investigate the changes of serum IL-2, IL-6 and TNF-α levels after one month of comprehensive treatment in patients with periodontitis. Methods: Serum IL-2, IL-6 and TNF-α levels were measured with RIA in 48 patients with periodontitis both before and after treatment as well as in 35 controls. Results: Before treatment, serum levels of IL-6, TNF- α in the patients were significantly higher and IL-2 levels were significantly lower than those in the controls (both P 0.05). However, the IL-2 levels were still significantly lower than those in controls (P<0.05). Conclusion: There was disturbance of immuno-modulation in patients with periodontitis as expressed by the changes of cytokines levels in the course of the disease. (authors)

La prolusione di rocco e le dottrine del processo penale

Directory of Open Access Journals (Sweden)

Renzo Orlandi

2015-03-01

Full Text Available L’articolo analizza le conseguenze del pensiero giuridico di Arturo Rocco, dal 1910 nella dottrina di procedura penale, ossia, il metodo tecnico-giuridico (esegesi, sistematica e critica. La dogmatica di procedura pena- le inizia con la monografia di Giovanni Conso, nel 1955. L’insoddisfazione con il tecnicismo giuridico e con la mancanza di maturità scientifica si è manifestata con Carnelutti nel 1946 (Cerenterola, sottolineando le peculiarità strutturali del procedimento penale. In questa prospettiva, il testo sottolinea la conferenza di Franco Cordero nel 1964 (Lecce, così come le lezioni da James Goldschmidt. Inoltre, negli anni sessanta, divennero importanti diritti fondamentali, di fronte alla Costituzione democratica, con un nuovo orientamento dottrinale. Il diritto processuale penale è stato considerato come diritto costituzionale applicato. Si segnalano gli insegnamenti di Amodio, Amato, Chiavario, Ferrua, Grevi, Iluminati, Massa e Nobili. Successivamente, l’articolo mette in evidenza il CPP del 1988, l’internazionalizzazione dei sistemi giuridici, l’importanza del diritto comparato e dei diritti fondamentali. Si conclude con il nuovo ordine mondiale dei diplomi internazionali e tribunali sovranazionali, con nuove esigenze, oltre il tecnicismo giuridico.

Intrathymic radioresistant stem cells follow an IL-2/IL-2R pathway during thymic regeneration after sublethal irradiation

International Nuclear Information System (INIS)

Zuniga-Pfluecker, J.C.K.; Kruisbeek, A.M.

1990-01-01

Sublethally irradiated mice undergo thymic regeneration which follows a phenotypic pattern of events similar to that observed during normal fetal development. Thymic regeneration after irradiation is the product of a limited pool of intrathymic radioresistant stem cells undergoing simultaneous differentiation. We show that in this model of T cell development, thymic regeneration follows a pathway in which the IL-2R is transiently expressed on CD4-/CD8- cells. IL-2R expression occurred during the exponential growth period of thymic regeneration, and IL-2R blocking prevented this explosive growth. Flow cytometry analysis revealed that the IL-2R blockade affected primarily the development of the immature CD3-/CD4-/CD8- (triple negative) cells and their ability to generate CD3+/CD4+/CD8+ or CD3+/CD4+/CD8- and CD3+/CD4-/CD8+ thymocytes. Thus, our findings demonstrate that blocking of the IL-2R resulted in an arrest in proliferation and differentiation by intrathymic radioresistant stem cells, indicating that the IL-2/IL-2R pathway is necessary for the expansion of immature triple negative T cells

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

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)

“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.

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.

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.

Elevated levels of IL-6 and IL-18 in manic and hypomanic states in rapid cycling bipolar disorder patients

DEFF Research Database (Denmark)

Munkholm, Klaus; Weikop, Pia; Kessing, Lars Vedel

2015-01-01

obtained in affective states of varying polarity during 6-12 months in 37 rapid cycling bipolar disorder patients and compared with repeated measurements in 40 age- and gender matched healthy control subjects, using rigorous laboratory-, clinical- and statistical methodology. Adjusting for demographical...... were to assess alterations of peripheral cytokine levels between affective states in rapid cycling bipolar disorder patients and to compare these with levels in healthy control subjects. In a longitudinal design, repeated measurements of plasma levels of IL-6, IL-10, IL-18, IL-1β and TNF-α were......, clinical- and lifestyle factors, levels of IL-6 (prapid cycling bipolar disorder patients in a manic/hypomanic state, compared with a depressed and a euthymic state. Compared with healthy control subjects, unadjusted levels of IL-6 (p

Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

Directory of Open Access Journals (Sweden)

Julia Diegelmann

Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

Increased Parenchymal Damage and Steatohepatitis in Caucasian Nonalcoholic Fatty Liver Disease Patients with Common IL1B and IL6 Polymorphisms

Science.gov (United States)

Nelson, James E.; Handa, Priya; Aouizerat, Bradley; Wilson, Laura; Vemulakonda, L Akhila; Yeh, Matthew M.; Kowdley, Kris V.

2016-01-01

Background Nonalcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1β and IL-6 have been shown to be elevated in nonalcoholic steatohepatitis (NASH). The goal of this study was to investigate the relationship between IL1B and IL6 gene polymorphisms and histologic features of NAFLD in the NASH CRN cohort. Methods 604 adult (≥18 yrs) non-Hispanic Caucasians with biopsy-proven NAFLD were genotyped for the following SNPs: IL1B, rs16944, rs1143634; IL6, rs1800795, rs10499563. Logistic regression was used to examine the relationship between genotype and a definitive diagnosis and advanced histological features of NASH after controlling for the following variables selected a priori: age, sex, diabetes, obesity and HOMA-IR level. Results The IL6 rs10499563 C allele was independently associated with the presence of definitive NASH, and increased ballooning and Mallory bodies. The IL1B rs1143634 TT genotype was associated with advanced fibrosis and increased Mallory bodies. The IL6 rs1800795 C allele was associated with increased risk for severe steatosis, >66% but also decreased risk for advanced fibrosis and lobular inflammation and Mallory body formation. Conclusions These results suggest that common variants in the IL6 and IL1B genes may increase susceptibility for NASH and confer a higher risk of hepatic parenchymal damage including increased ballooning, increased Mallory bodies, and bridging fibrosis or cirrhosis. In contrast, the IL6 rs1800795 C allele may confer a higher risk for steatosis, but less parenchymal damage. Our findings support the development of therapeutics aimed at IL-1β and IL-6 suppression. PMID:27730688