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Sample records for bassa entalpia il

  1. Book Review: Dams, displacement, and the delusion of development: Cahora Bassa and its legacies in Mozambique, 1965–2007

    CSIR Research Space (South Africa)

    Meissner, Richard

    2015-10-01

    Full Text Available Journal of International Affairs Book Review: Dams, displacement, and the delusion of development: Cahora Bassa and its legacies in Mozambique, 1965–2007 Richard Meissner Council for Scientific and Industrial Research, Pretoria, South Africa...

  2. Heavy metal concentrations and distribution in surface soils of the Bassa Industrial Zone 1, Douala, Cameroon

    International Nuclear Information System (INIS)

    Asaah, Victor A.; Abimbola, Akinlolu F.; Suh, Cheo E.

    2006-01-01

    Partial extraction was carried out on 33 soil samples collected from the Bassa Industrial Zone 1, Douala, Cameroon. From the samples analyzed the following metal concentrations (range) were obtained (in ppm): Ag (0-1.3), As (0-64), Cd(0-7.3), Co(0-31), Cr(34-423), Cu(12-909), Mn(55-3282), Mo(0-81.6), Ni(9-284), Pb (0-3320), Sb (0-30), Sc (0.6-7.5), V (26-110), Zn (30-3782) and Fe (in wt%) (1.50-47.31). Results obtained reveal background and anomalous populations for most of the metals except Sc and V, which have only background populations. Multi-element geochemical anomalies occur within the vicinity of industries, waste dump sites, metal workshops and mechanical workshops. R-mode factor analysis reveals three element associations and two singular elements (As, Cd) accounting for 94% of the total data variance. The three associations are: Ag-Cu-Cr-Fe-Mn-Mo-Ni-Sb; Co-Cu-Pb-Sb-Zn and Sc-V. The geoaccumulation indices show that soils in the Bassa Industrial Zone are moderately to very highly pollute. These metal-laden soils constitute a major health risk to the local population and a cause for concern. This study successfully relates the concentration and distribution of toxic metals in the soils of Bassa Industrial Zone to urban effluents generated mainly from industrial activities. (author)

  3. Comuni in guerra. Amministrazione, popolazione e risorse nella Bassa Romagna

    Directory of Open Access Journals (Sweden)

    Elisa Dondi

    2016-11-01

    Full Text Available Presentiamo gli esiti di una ricerca svolta negli archivi storici comunali di Massa Lombarda, Russi e Bagnacavallo sul tema dell'alimentazione durante la seconda guerra mondiale. Si sono analizzate le funzioni affidate ai Comuni, le condizioni alimentari dei tre comuni rurali e le reazioni alle privazioni della popolazione. Attraverso lo studio di un caso locale abbiamo cercato di cogliere gli aspetti generali che caratterizzano il vettovagliamento del fronte interno italiano.

  4. Misure in laboratorio di acustica edilizia a bassa frequenza: un approccio modale - Laboratory measurements of building acoustics at low frequency: a modal approach

    Directory of Open Access Journals (Sweden)

    Andrea Prato

    2016-07-01

    Full Text Available Nei tipici ambienti ordinari e di laboratorio (40-80 m3 e a bassa frequenza (50-100 Hz, il campo acustico risulta non diffuso a causa della presenza dei modi. In tali condizioni, le misure classiche di acustica edilizia (isolamento acustico per via aerea e da impatto, tempi di riverbera-zione sono inadeguate per caratterizzare correttamente le proprietà acustiche di partizioni, si-stemi di pavimentazioni e spazi chiusi. L’approccio modale permette di valutare tali proprietà studiando il comportamento dei modi. Sulla base di ciò, appropriate procedure di misura e nuovi descrittori sono proposti e discussi in modo da fornire possibili soluzioni per tali problematiche. ------ In typical laboratory and ordinary rooms (40-80 m3 and at low frequencies (50-100 Hz, the acoustic field is non-diffuse due to the presence of room modes. Under such conditions, standard building acoustics measurements (airborne and impact sound insulation, reverberation time and descriptors are not adequate to correctly characterize the acoustic property of partitions, flooring systems and rooms. The modal approach allows to evaluate such properties by studying the behavior of modes. On the basis of this, proper measurement procedures and new descriptors are proposed and discussed in order to provide possible solutions for such issues.

  5. Cahora Bassa and Tete Province (Mozambique): A great potential for an industrial hub in Southern Africa

    International Nuclear Information System (INIS)

    Sebitosi, A.B.; Graca, A. da

    2009-01-01

    Mozambique is host to the great Zambezi River Basin and the World Famous Cahora Bassa power plant that generates some 13,000 GWh annually. The bulk of this energy (85%) is exported but the revenue raised does not appear to have any appreciable impact on the host economy. Moreover it is estimated that a further 10% of the generated energy is lost along the 1414 km long transmission line to South Africa. So quite evidently, Mozambique would benefit more if its energy were utilized by locally based industry. This would also save on the losses that are currently incurred during regional transmission. In this paper the authors visit Tete, the Mozambican Province that hosts the Zambezi Basin. They examine its natural and human resources. They observe that its strategic location gives it easy access to regional markets. They also hold interviews with a number of administrators in the Province. Finally, they conclude that Tete is uniquely advantaged to develop into the next regional industrial hub for the Southern African region. This would also greatly add value to the local resources. To realize this dream will require, conviction supported by strong and timely political commitment as well as hard work. Current trends towards integrated regional trading blocks will provide an even easier access to potential markets and human skills pools.

  6. Il rumore elettrico Dalla fisica alla progettazione

    CERN Document Server

    Pallottino, Giovanni Vittorio

    2011-01-01

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

  7. Nuovi orizzonti sulle trasformazioni di fase a bassa temperatura negli acciai

    DEFF Research Database (Denmark)

    Villa, Matteo

    In termine “acciai” si riferisce a leghe contenenti almeno il 50% in peso di ferro assieme ad altri elementi chimici, tra cui carbonio in contenuto inferiore al 2.1% in peso. Inoltre, gli acciai sono classificati come ad alto contenuto di carbonio quando il contenuto in peso di questo elemento ec...

  8. Phytoremediation potential of weeds in heavy metal contaminated soils of the Bassa Industrial Zone of Douala, Cameroon.

    Science.gov (United States)

    Lum, A Fontem; Ngwa, E S A; Chikoye, D; Suh, C E

    2014-01-01

    Phytoremediation is a promising option for reclaiming soils contaminated with toxic metals, using plants with high potentials for extraction, stabilization and hyperaccumulation. This study was conducted in Cameroon, at the Bassa Industrial Zone of Douala in 2011, to assess the total content of 19 heavy metals and 5 other elements in soils and phytoremediation potential of 12 weeds. Partial extraction was carried out in soil, plant root and shoot samples. Phytoremediation potential was evaluated in terms of the Biological Concentration Factor, Translocation Factor and Biological Accumulation Coefficient. The detectable content of the heavy metals in soils was Cu:70-179, Pb:8-130, Zn:200-971, Ni:74-296, Co:31-90, Mn:1983-4139, V:165-383, Cr:42-1054, Ba:26-239, Sc:21-56, Al:6.11-9.84, Th:7-22, Sr:30-190, La:52-115, Zr:111-341, Y:10-49, Nb:90-172 in mg kg(-1), and Ti:2.73-4.09 and Fe:12-16.24 in wt%. The contamination index revealed that the soils were slightly to heavily contaminated while the geoaccumulation index showed that the soils ranged from unpolluted to highly polluted. The concentration of heavy metals was ranked as Zn > Ni > Cu > V > Mn > Sc > Co > Pb and Cr in the roots and Mn > Zn > Ni > Cu > Sc > Co > V > Pb > Cr > Fe in the shoots. Dissotis rotundifolia and Kyllinga erecta had phytoextraction potentials for Pb and Paspalum orbicularefor Fe. Eleusine indica and K. erecta had phytostabilisation potential for soils contaminated with Cu and Pb, respectively.

  9. Construção de um calorímetro de baixo custo para a determinação de entalpia de neutralização

    OpenAIRE

    Assumpção, M. H. M. T.; Wolf, L. D.; Bonifácio, V. G.; Fatibello-Filho, O.

    2010-01-01

    Neste artigo descreve-se a construção de um calorímetro simples, utilizando materiais de fácil aquisição, para a determinação de entalpia de neutralização (pressão constante) de reações ácido-base. Foram utilizadas para o desenvolvimento do experimento soluções de ácidos e bases fortes e fracos, além de termômetro e recipiente de poliestireno expandido (isopor) para a medida e manutenção da temperatura, respectivamente. Com este experimento, foi então possível determinar a entalpia de neutral...

  10. 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.

  11. Sviluppo di un nuovo trigger con identificazione di quark-b per il canale Z($\

    CERN Document Server

    Donato, Silvio

    La ricerca del decadimento del bosone di Higgs H -> b b è uno dei canali più importanti per verificare se la particella di massa 125 GeV circa, recentemente scoperto da ATLAS e CMS, corrisponde effettivamente al bosone di Higgs previsto dal Modello Standard. Questo decadimento, insieme a H -> tau tau, è fondamentale per misurare l'accoppiamento del bosone con i fermioni. Il fondo di QCD rende poco sensibile l'osservazione di questo decadimento nella produzione diretta del bosone di Higgs. Per questo motivo il decadimento H -> b b viene ricercato quando l'Higgs è prodotto in associazione con i bosoni vettore W/Z, attraverso il cosiddetto processo di ``Higgs-strahlung''. Il decadimento leptonico dei bosoni vettore ad alto pT permette di ridurre il fondo di QCD e di realizzare trigger per osservare il canale. In questa tesi è stato realizzato un trigger per osservare il canale H + Z -> b b + nu nu nella regione a bassa EtMiss (fino a 80 GeV) con l'esperimento CMS. Per avere il trigger con un rate accettabi...

  12. Enthalpy-entropy compensation based on isotherms of mango Compensação entalpia-entropia baseada nas isotermas de mango

    Directory of Open Access Journals (Sweden)

    Javier Telis-Romero

    2005-06-01

    Full Text Available Moisture equilibrium data of mango pulp were determined using the static gravimetric method. Adsorption and desorption isotherms were obtained in the range of 30-70 ºC, to water activities (a w from 0.02 to 0.97. The application of the GAB model to the experimental results, using direct nonlinear regression analysis, provided agreement between experimental and calculated values. The net isosteric heat of sorption was estimated from equilibrium sorption data, using the Clausius-Clapeyron equation. Isosteric heats of sorption were found to increase with increasing temperature and could be well adjusted by an exponential relationship. The enthalpy-entropy compensation theory was applied to sorption isotherms and plots of deltaH versus deltaS provided the isokinetic temperatures, indicating an enthalpy controlled sorption process.Dados de equilíbrio da umidade da polpa de manga foram determinados utilizando-se o método estático gravimétrico. As isotermas de adsorção e dessorção foram obtidas na faixa de 30-70 ºC e as atividades de água (a w de 0,02 a 0,97. A utilização do modelo de GAB nos resultados experimentais, através da análise de regressão não linear, proporcionou um bom ajuste entre os dados experimentais e os valores calculados. O calor isostérico de sorção foi estimado a partir dos dados de equilíbrio de sorção, utilizando-se a equação de Clausius-Clayperon. Notou-se que os calores isostéricos de sorção crescem com o aumento da temperatura e pode ser bem ajustado através de uma relação exponencial. A teoria da compensação entalpia-entropia foi aplicada às isotermas de sorção e gráficos deltaH versus deltaS forneceram as temperaturas isocinéticas, indicando um processo de sorção entalpicamente controlado.

  13. Il Gioco

    Directory of Open Access Journals (Sweden)

    David Beronio

    2016-02-01

    Full Text Available Chi si occupa di teatro incontra il gioco innanzitutto come una categoria estetica insita nei processi che caratterizzano l’atto teatrale. Ma dall’approfondimento di tali meccanismi emerge anche la potenzialità conoscitiva del gioco, come condizione umana di profonda consapevolezza di sé. Attraverso un percorso che passa attraverso Breton, Platone, Huizinga, e Alessandro Fersen, viene qui proposta una lettura del gioco come carattere fondamentale dell’arte e della conoscenza.

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

    Science.gov (United States)

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

    2015-01-01

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

  15. Screenings of lung cancer with low dose spiral CT: results of a three year pilot study and design of the randomised controlled trial Italung-CT; Screening della neoplasia polmonare con TC spirale a bassa dose: risultati di uno studio pilota triennale e disegno dello studio clinico randomizzato Italung-CT

    Energy Technology Data Exchange (ETDEWEB)

    Picozzi, Giulia [Firenze Univ., Firenze (Italy). Radiodiagnostica I-Dipartimento di Fisiopatologia Clinica; Paci, Enrico [Azienda Ospedaliera Universitaria di Careggi, Firenze (Italy). Unita' di Epidemiologia Clinica e Descrittiva Centro per lo Studio e la Prevenzione Oncologica; Lopes Pegna, Andrea [Azienda Ospedaliera Universitaria di Careggi, Firenze (Italy). U.O. Pneumologia] [and others

    2005-02-01

    Purpose: To report the results of a three-year observational pilot study of lung cancer screening with low dose computed tomography (CT) and to present the study design of a randomised clinical trial named as Italung CT. Materials and methods: Sixty (47 males and 13 females, mean age 64{+-}4.5 years) heavy smokers (at least 20 packs-year) underwent three low-dose spiral CT screening tests one year apart on a single slice or multislice CT scanner. Indeterminate nodules were managed according to the recommendations of the Early Lung Cancer Action Project. Results: Indeterminate nodules were observed in 33 (55%) of the subjects (60% at the baseline screening test, 24% at the first annual test and 16% at the second annual test). The size of the largest indeterminate nodule was <5mm in diameter in 20 subjects. 10 of whom showed the nodule at the baseline test. Forty-five subjects (75%) completed the first annual test and 42 (70%) the second annual test. One (1.6%) prevalent lung cancer (adenosquamous carcinoma) and one (2.2%) incident lung cancer (small cell cancer at the first annual examination) were observed, as well as pulmonary localisation of Hodgkin's lymphoma (at the second annual test). In addition, one subject underwent lung surgery for a chondromatous hamartoma. Conclusions: The results of the pilot study are substantially in line with those of other observational studies of greater sample size. This justifies optimism about the reliability of the results in the screened arm of the Italung Ct trial which hast just began. [Italian] Scopo: Riportare i risultati di uno studio pilota osservazionale di screening della neoplasia polmonare con TC a bassa dose della durata di tre anni e presentare il disegno dello studio clinico randomizzato Italung-CT. Materiale e metodi: Sessanta (47 uomini e 13 donne, eta' media 64{+-}4,5 anni) forti fumatori (almeno 20 pacchetti/anno) sono stati sottoposti ad un esame basale e a due controlli annuali con TC single o

  16. Il mondo dentro il mondo

    CERN Document Server

    Barrow, John D

    1991-01-01

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

  17. Treatment of toxic and hazardous organic wastes by wet oxidation process with oxygenated water at low temperature; Trattamento dei rifiuti tossici e nocivi organici mediante il processo di ossidazione ad umido con acqua ossigenata a bassa temperatura

    Energy Technology Data Exchange (ETDEWEB)

    Piccinno, T; Salluzzo, A; Nardi, L [ENEA - Dipartimento Ciclo del Combustibile, Centro Ricerche Energia, Casaccia (Italy); Gili, M; Luce, A; Troiani, F [ENEA - Dipartimento Ciclo del Combustibile, Centro Ricerche Energia, Saluggia (Italy); Cornacchia, G [ENEA - Dipartimento Ciclo del Combustibile, Centro Ricerche Energia, Trisaia (Italy)

    1989-11-15

    The wet oxidation process using air or molecular oxygen is a well-known process from long time. It is suitable to oxidize several types of waste refractory to the usual biological, thermal and chemical treatments. The drastic operating conditions (high pressures and temperatures) prevented its industrial development. In the last years a new interest was assigned to the process for the treatment of nuclear wastes (organic resins and exhaust organic wastes); the treatment is carried out at widely reduced operating conditions (atmospheric pressure and boiling temperature) by means of metallic catalysts and hydrogen peroxide. With some limits, the wet oxidation with hydrogen peroxide at low temperature can be applied to conventional waste waters containing toxic organic compounds. In the present report are summarized the activities developed at ENEA Fuel Cycle Department by the task force 'Deox' constituted by laboratory and plant specialists in order to verify the application of the wet oxidation process to the treatment of the toxic wastes. (author)

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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 ...

  3. 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

  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.

  5. 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

  6. 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.

  7. 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.

  8. Il dono del racconto

    DEFF Research Database (Denmark)

    Polito, Paola

    1998-01-01

    L'articolo indaga a vari livelli strutturali del romanzo "Il coraggio del pettirosso" (rete metaforica, dialogismo diegetico, dialogismo come fenomeno di voce, strategie discorsive messe in atto dalla voce narrante, stile colloquiale) la complessa realizzazione testuale del genere narrativo...

  9. Il Primo Dizionario

    Directory of Open Access Journals (Sweden)

    Minne G. de Boer

    2015-07-01

    Full Text Available Recensione e commento a: Il Primo Dizionario italiano-olandese/Het Eerste Woordenboek Nederlands-Italiaans, Amsterdam 1672/2014, a cura di Vincenzo Lo Cascio. Amstelveen: Fondazione

  10. 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

  11. 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.

  12. 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 .

  13. 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.

  14. 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.

  15. 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....

  16. Dostoevskij e il sillogismo

    Directory of Open Access Journals (Sweden)

    Richard Peace

    2013-12-01

    Full Text Available Si presenta di seguito la prima traduzione italiana del saggio di Richard Peace Dostoevsky and the Syllogism, pubblicato in lingua originale nel volume IX (2005 della collana Dostoevsky Studies, New Series. Il saggio è dedicato alla rielaborazione del sillogismo aristotelico da parte dei personaggi dostoevskiani nell’ambito del dibattito fra le due principali correnti filosofiche della Russia ottocentesca: l’ «occidentalismo» e lo «slavofilismo». Peace evidenzia come Dostoevskij miri a dimostrare che il ragionamento sillogistico sia estraneo alla forma mentis russa attraverso i fallimenti argomentativi dei suoi «ideofori»

  17. 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.

  18. Il Raffrescamento per Ventilazione

    DEFF Research Database (Denmark)

    Perino, Marco; Heiselberg, Per Kvols

    2016-01-01

    termicamente e sempre più a tenuta d'aria. Tali misure hanno consentito indubbiamente di ridurre la domanda energetica per il riscaldamento invernale, ma hanno determinato delle crescenti problematiche di surriscaldamento dell'ambiente interno. Molti degli edifici ad alta efficienza energeti-ca di nuova...

  19. Helping You Buy ILS

    Science.gov (United States)

    Cibbarelli, Pamela R.

    2010-01-01

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

  20. Il pericolo degli ebook

    Directory of Open Access Journals (Sweden)

    Maria Chiara Pievatolo

    2014-01-01

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

  1. Il Simposio di Platone

    Directory of Open Access Journals (Sweden)

    Maria Chiara Pievatolo

    2013-01-01

    Full Text Available Pensate che i testi antichi siano semplicemente vecchi? Che l’amore platonico non vada mai  al sodo? Leggere il Simposio di Platone confrontandosi direttamente col testo, com’è possibile fare grazie al Perseus Project, vi farà cambiare idea.

  2. 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.

  3. 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.

  4. 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...

  5. Il libro di fisica

    CERN Document Server

    Asimov, Isaac

    1986-01-01

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

  6. 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...

  7. 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.

  8. Il GEOatleta moderno

    Directory of Open Access Journals (Sweden)

    Francesco Bartoli

    2006-12-01

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

  9. Il muro nella mente:

    Directory of Open Access Journals (Sweden)

    Carmen Concilio

    2013-07-01

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

  10. Il bilinguismo disegnato

    Directory of Open Access Journals (Sweden)

    Graziella Favaro

    2013-07-01

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

  11. 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)

  12. 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...

  13. 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

  14. 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 ...

  15. 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. 

  16. Mimesis e il giallo

    Directory of Open Access Journals (Sweden)

    Minne de Boer

    2015-12-01

    Full Text Available Recensione di: Ilaria Marzia Orsini, Donne in giallo: la detective story tra genere e gender, Milano/Udine, Mimesis/DeGenere – USB Ultra Slim Books, 2014, 128 p., ISBN: 97888575245680, € 11,00. Bruna Durante, Specchio delle mie trame: la vita secondo dieci scrittori italiani. Con interviste a Eraldo Baldini, Gianni Biondillo, Giancarlo De Cataldo, Giorgio Faletti, Marcello Fois, Carlo Lucarelli, Raul Montanari, Santo Piazzese, Andrea G. Pinketts, Gaetano Savatteri, Milano/Udine, Mimesis/DeGenere, 2014, 180 p., ISBN: 9788857518176, € 13,60.Carlo Oliva, Giallo popolare: il poliziesco alla radio, a cura di Nicoletta Di Ciolla e Nicoletta Vallorani, Milano/Udine, Mimesis/DeGenere, 2013, 150 p., ISBN: 9788857518183, € 12,00.

  17. Il GEOatleta moderno

    Directory of Open Access Journals (Sweden)

    Francesco Bartoli

    2006-12-01

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

  18. Il cumulo dei redditi.

    Directory of Open Access Journals (Sweden)

    V. BARATTIERI

    2014-08-01

    Full Text Available L’imposizione dei redditi familiari è diffusa nella maggior parte dei paesi sviluppati, seppure con varianti profondamente diverse per mitigare l’onere. La tassazione separata è in vigore solo in Canada, Grecia e Nuova Zelanda, on chè , tra i paesi latini, in Argentina. Non sempre però la tassazione separata risulta più favorevole, in quanto alcune forme peculiari del cumulo, quali “splitting” ed il quoziente familiare, consentono un trattamento preferenziale per le famiglie rispetto ai nn coniugati. I vantaggi del quoziente familiare sono ancora maggiori , specie per le famiglie numerose, e questo sembra anacronistico in un momento in cui vi è larga convergenza d’opinioni sull’opportunità di non incoraggiare l’espansione demografica.

  19. 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 ...

  20. 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.

  1. 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

  2. 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

  3. 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)

  4. IL CAMPO GEOMAGNETICO

    Directory of Open Access Journals (Sweden)

    F. MOLINA

    1972-06-01

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

  5. 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.

  6. 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

  7. 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.

  8. Il marketing del nuovo millennio

    OpenAIRE

    M. Addis

    2007-01-01

    Con la consueta maestria, Kolter, supportato da Keller, mette a disposizione dei suoi numerosi lettori uno strumento di grande efficacia, dalla struttura estremamente agile, che potrà essere apprezzato da coloro che il marketing lo insegnano e dai professionisti che cercano un'opera di riferimento autorevole e aggiornata ma al contempo di facile consultazione, che possa accompagnarli nello svolgimento delle attività quotidiane. Il testo è una guida essenziale alla disciplina del marketing,...

  9. 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.

  10. 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.

  11. 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.

  12. Il libro agente della socializzazione

    Directory of Open Access Journals (Sweden)

    Daniela Sideri

    2017-06-01

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

  13. Il potere di Prometeo e il dovere di Kant

    Directory of Open Access Journals (Sweden)

    Stefano Picchetti

    2006-10-01

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

  14. 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...

  15. Il programma dell'universo

    CERN Document Server

    Lloyd, Seth

    2006-01-01

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

  16. 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....

  17. 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.

  18. 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)

  19. Pauropolis. Pianificare il controllo attraverso il progetto della sicurezza.

    OpenAIRE

    Ragonese, Marco

    2008-01-01

    2006/2007 “Il grado di sicurezza misura la democrazia di un paese”, con questa frase un esponente della destra salutava l’approvazione nel parlamento italiano del nuovo pacchetto di norme in tema, appunto, di sicurezza. L’affermazione indica sintomaticamente come la questione, seppur non nuova, abbia acquisito un ruolo centrale nel dibattito contemporaneo, facilitata da una perfusione mediatica che ha trasformato l’evento dei primi giorni del settembre 2001 nel simbolo controverso della cr...

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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...

  6. Estimation of production characteristic curves of geothermal wells and of the permeability of rocky formations through one single mass flow-pressure-enthalpy (W-P-h) measurement at the wellhead; Estimacion de curvas caracteristicas de produccion de pozos geotermicos y de permeabilidades de formaciones rocosas a partir de una sola medicion flujo masico-presion- entalpia (W-P-h) a boca de pozo

    Energy Technology Data Exchange (ETDEWEB)

    L Moya, Sara; Aragon, Alfonso [Instituto de Investigaciones Electricas, Cuernavaca (Mexico)

    1997-12-31

    The proposed methodology described ahead (Moya et al.,1996; Moya et al.,1997a, 1997b and 1997c) simplifies the construction of production characteristic curves of geothermal wells and of its associated thermal productivity, in requiring one single measurement of mass flow-pressure-enthalpy (W-P-h) at the wellhead. Therefore it is an ecological option, technically and economically more feasible. On the other hand, the methodology also allows to diagnose the rocky formation absolute permeability in the well feeding zone. This permeability is usually determined through well bottom pressure tests, than in some cases are difficult to interpret. The permeability inferred by means of the proposed technology represents a complementary tool for these field tests and for the laboratory measurements on drilling cores. [Espanol] La metodologia propuesta que se describe a continuacion [Moya et al., 1995d; Moya et al., 1996; Moya et al., 1997a, 1997b y 1997c] simplifica la construccion de curvas caracteristicas de produccion de pozos geotermicos y de su productividad termica asociada al requerir solo una medicion de flujo masico-presion-entalpia (W-P-h) a boca de pozo. Es por tanto una alternativa ecologica, tecnica y economicamente mas factible. Por otra parte, la metodologia tambien permite diagnosticar el valor de la permeabilidad absoluta de la formacion rocosa en la zona de alimentacion al pozo. Esta permeabilidad se determina usualmente a partir de pruebas de presion a fondo de pozo que en algunos casos son dificiles de interpretar. La permeabilidad inferida mediante la metodologia propuesta representa una herramienta complementaria a estas pruebas de campo y a las mediciones de laboratorio sobre nucleos de perforacion.

  7. Estimation of production characteristic curves of geothermal wells and of the permeability of rocky formations through one single mass flow-pressure-enthalpy (W-P-h) measurement at the wellhead; Estimacion de curvas caracteristicas de produccion de pozos geotermicos y de permeabilidades de formaciones rocosas a partir de una sola medicion flujo masico-presion- entalpia (W-P-h) a boca de pozo

    Energy Technology Data Exchange (ETDEWEB)

    L Moya, Sara; Aragon, Alfonso [Instituto de Investigaciones Electricas, Cuernavaca (Mexico)

    1998-12-31

    The proposed methodology described ahead (Moya et al.,1996; Moya et al.,1997a, 1997b and 1997c) simplifies the construction of production characteristic curves of geothermal wells and of its associated thermal productivity, in requiring one single measurement of mass flow-pressure-enthalpy (W-P-h) at the wellhead. Therefore it is an ecological option, technically and economically more feasible. On the other hand, the methodology also allows to diagnose the rocky formation absolute permeability in the well feeding zone. This permeability is usually determined through well bottom pressure tests, than in some cases are difficult to interpret. The permeability inferred by means of the proposed technology represents a complementary tool for these field tests and for the laboratory measurements on drilling cores. [Espanol] La metodologia propuesta que se describe a continuacion [Moya et al., 1995d; Moya et al., 1996; Moya et al., 1997a, 1997b y 1997c] simplifica la construccion de curvas caracteristicas de produccion de pozos geotermicos y de su productividad termica asociada al requerir solo una medicion de flujo masico-presion-entalpia (W-P-h) a boca de pozo. Es por tanto una alternativa ecologica, tecnica y economicamente mas factible. Por otra parte, la metodologia tambien permite diagnosticar el valor de la permeabilidad absoluta de la formacion rocosa en la zona de alimentacion al pozo. Esta permeabilidad se determina usualmente a partir de pruebas de presion a fondo de pozo que en algunos casos son dificiles de interpretar. La permeabilidad inferida mediante la metodologia propuesta representa una herramienta complementaria a estas pruebas de campo y a las mediciones de laboratorio sobre nucleos de perforacion.

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

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    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.

  9. 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.

  10. 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.

  11. Biological significance of soluble IL-2 receptor

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    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

  12. Il gioco le leggi naturali governano il caso

    CERN Document Server

    Eigen, Manfred

    1986-01-01

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

  13. 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

  14. 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)

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

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    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.

  16. I lectores medioevali tra il libro e il testo

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    Federica Riviello

    2012-06-01

    Full Text Available L’intento del lavoro è di problematizzare alcuni aspetti, generalmente ritenuti emblematici, della relazione tra i litterati medievali e il libro – nelle sue declinazioni di Testo sacro, Libro della natura e auctoritates. L’impiego, come strumenti di lavoro, di concetti di recente elaborazione e di osservazioni di pensatori contemporanei sull’argomento, non è finalizzato ad attualizzare tale relazione, quanto piuttosto ad ampliare i punti di vista su di essa e a metterne alla prova la capacità di offrire originali spunti di riflessione. Le proposte teoriche di Jacques Derrida, Michel Foucault e Roland Barthes sono qui adoperate come esemplificazioni di un’interpretazione che ha storicamente reso quasi paradigmatico il modo di leggere dei docti, specialmente altomedievali. Tuttavia, alcune definizioni della Scrittura – il libro per eccellenza – proposte da questi ultimi, nonché la teorizzazione del suo quadruplice senso sembrano smussare la radicalità di queste osservazioni. Concetti quali “funzione-autore” di Foucault e “testo” di Barthes sono invece adottati per considerare all’interno di una diversa cornice teorica il confronto dei doctores, in particolare bassomedievali, con le cosiddette auctoritates. Nella visione ordinaria la reverenza nei confronti dell’autore, divino o umano, la ricerca e la riproposizione fedele di un significato univoco dell’opera aldilà dei segni, naturali o culturali, che lo veicolano costituiscono tratti tipici dell’atteggiamento dei lettori medievali. A fronte di questi aspetti, tuttavia, è possibile sottolinearne altri eterodossi e perlopiù trascurati, quali la rilevanza attribuita all’interpretazione, prassi ineludibile e da disciplinare, al ruolo del lettore e alla sua fruizione attiva e produttiva dei testi. The aim of the work is to problematize some aspects generally considered representative of the relationship between medieval savants and the book - in its variations

  17. IL-21 Receptor Expression in Human Tendinopathy

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    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.

  18. 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.

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

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    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.

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

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    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.

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

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    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.

  2. 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.

  3. 25-Hydroxyvitamin D, IL-31, and IL-33 in Children with Allergic Disease of the Airways

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    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.

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

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    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.

  5. 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.

  6. Il Gambling Compulsivo: rilevanza epidemiologica

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    A. Coacci

    2003-05-01

    Full Text Available

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

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

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

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

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

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

  7. 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...

  8. 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

  9. Il fuoco della fusione termonucleare controllata

    CERN Document Server

    Caldirola, Piero; Sindoni, Elio

    1984-01-01

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

  10. IL-6 Receptor Isoforms and Ovarian Cancer

    Science.gov (United States)

    2013-01-01

    grown these cells in culture and have generated stable cell clones which express Tomato Red so that these cells can be followed through fluorescent...occurring in ovarian cell lines, we examined the effect of IL6 and IL6Ra expression on cell migration in vitro . Migration through uncoated cell culture ...or IL6R were plated on tissue culture plates and scratch wounds were made. Over the course of the experiment, photographs of the cultures were

  11. Il viaggio gastronomico di Paolo Monelli.

    OpenAIRE

    Salarelli, Alberto

    2013-01-01

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

  12. 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...

  13. Sinergetica il segreto del successo della natura

    CERN Document Server

    Haken, Hermann

    1983-01-01

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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. FISH PRODUCTION ESTIMATES FOR GBEDIKERE LAKE, BASSA, KOGI STATE, NIGERIA

    Directory of Open Access Journals (Sweden)

    Samuel Olusegun Adeyemi

    2013-10-01

    Full Text Available Annual estimates of the fish caught by local fishermen in randomly selected fishing villages adjacent to Gbedikere Lake were determined using Catch Assessment (CAS. The studies were carried out within two seasons of low water (February and high water (September periods between 2006 to 2008. Annual fish catch varied from 537.4 mts to 576.9 mts at high water. Mean catch per boat ranged from 7.40 kg to 10.60 kg among the landing sites. A total of 12 fish species were identified belonging to ten families. The catches were dominated by the cichlids with Orechromis niloticus dominating the overall catch compositions. Production estimate was compared with the catches obtained through experimental gill-net sampling and potential fish yield estimates using Ryder’s Morpho - Edaphic Index (MEI as modified by Henderson and Welcomme (1974. Contributions of the gears in use were also done with cast nets ranking above others (29%, followed by the set net (25%, hook and lines (16.6%, traps (16.6%, clap net (8.3%. Management measures were suggested.

  19. 92 Negativization in Bassa Language Imoh Philip Manda* Abstract ...

    African Journals Online (AJOL)

    Ike Odimegwu

    three basic strategies used in negativizing sentence structures, two of which attach to the ... knowledge in the linguistic literature and create an awareness of how it operates in ... and morphosyntactic theories iv. ... Morava (1977:168) quotes.

  20. Cabora Bassa Fish Populations Before and During the First Filling ...

    African Journals Online (AJOL)

    Of a maximum of 38 species found one, Sarotherodon andersoni, was a new Middle Zambezi record. Lotic and shallow-water ... Soon after closure the first year-class predominated over all other age-groups; these juveniles, and small adult species, concentrated under mats of Elchhomia crassipes. One further species new ...

  1. 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.

  2. 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)

  3. 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)

  4. [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.

  5. 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...

  6. 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.

  7. 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.

  8. 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

  9. Knocking out IL-6 by vaccination

    DEFF Research Database (Denmark)

    Galle, Pia; Hougs, Lotte; Barington, Torben

    2004-01-01

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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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)

  16. 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.

  17. 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...

  18. 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.

  19. 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.

  20. 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

  1. 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)

  2. 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.

  3. 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

  4. Caravaggio e il Maccheronico di Teofilo Folengo

    Directory of Open Access Journals (Sweden)

    Bernardo Piciché

    2013-06-01

    Full Text Available Il presente studio ipotizza un’affinità tra Caravaggio e Teofilo Folengo, argomentando che la pittura del primo presenta analogie estetiche e etiche con la produzione in latino maccheronico del secondo. Il Baldus costituisce un tipico esempio di quella che Genette definirà come «parodia seria»: attraverso il rovesciamento e la irrisione beffarda Folengo ingaggia tenzone contro l’arte paludata e il travisamento dei valori cristiani. Non si tratta qui di stabilire un’influenza di Folengo su Caravaggio, bensì un’analogia, in virtù di un filo di congiunzione ideale, la cui presumibilità viene corroborata anche dal substrato biografico-culturale e da comune spirito religioso. Sia in Folengo che in Caravaggio sono stati individuati i caratteri di un certo modo della cultura lombarda di essere “contro” al punto che il duo Folengo-Caravaggio sembra epitomizzare l’antitesi al decorum curialcortigianesimo di Castiglione e Raffaello. Il Cristo-paradosso costituisce la vera fonte ispiratrice per entrambi. La comparazione tra due arti deve tenere conto dei diversi strumenti espressivi, e questo costituirà uno dei soggetti di riflessione nel testo. Se l’ipotesi della consentaneità viene ragionevolmente difesa, perché non individuare una componente maccheronica anche nell’arte di Caravaggio? Agli storici d’arte, tuttavia, decidere se si possa considerare il maccheronico come categoria pittorica

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. Tecnologia italiana per il vuoto spinto

    CERN Document Server

    2002-01-01

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

  11. Michel Foucault e il problema della genealogia

    Directory of Open Access Journals (Sweden)

    Enrico Abeni

    2011-01-01

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

  12. PER ALDO NOSEDA: IL CRITICO MUSICALE

    Directory of Open Access Journals (Sweden)

    Chiara Fiaccadori

    2014-03-01

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

  13. 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.

  14. Il viaggio gastronomico di Paolo Monelli

    Directory of Open Access Journals (Sweden)

    Alberto Salarelli

    2013-01-01

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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    Paolo Intoccia

    2017-11-01

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

  1. 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...

  2. 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

  3. 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.

  4. 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.

  5. 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)

  6. 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.

  7. 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.

  8. 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%.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

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

    NARCIS (Netherlands)

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

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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  1. [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.

  2. 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.

  3. 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.

  4. 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

  5. IL-8 as antibody therapeutic target in inflammatory diseases

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    DEFF Research Database (Denmark)

    Forslind, K; Svensson, Birte; Svenson, M

    2001-01-01

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

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

    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....

  8. 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...

  9. 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

  10. 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

  11. 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/.

  12. 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.

  13. 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

  14. Playware e robotica modulare per il gioco

    Directory of Open Access Journals (Sweden)

    Henrik H. Lund

    2009-01-01

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

  15. Il corpo, lo sport, le immagini

    Directory of Open Access Journals (Sweden)

    Nicola Porro

    2009-07-01

    Full Text Available E’ stato per primo Norbert Elias, nella sua critica al riduzionismo sociologico, a lamentare la difficoltà delle scienze sociali a misurarsi con le problematiche dello sport, così come delle emozioni, della sessualità, del gioco e della guerra. Attività umane che convergono in quell’autentico luogo sociale che è il corpo. Nel caso che ci interessa, si tratta di connettere il corpo, nella sua dimensione biologica, psichica e sociale, con quell’aspetto cruciale della civilizzazione che Elias definisce sportivizzazione.

  16. 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.

  17. 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...

  18. Il diritto al ricongiungimento familiare e la sua tutela multilivello

    OpenAIRE

    BANA, SOKOL

    2013-01-01

    L’unità familiare rappresenta, ovviamente, uno dei diritti primari della persona e il ricongiungimento familiare può ascriversi all’insieme di garanzie giuridiche poste a tutela della famiglia, intesa quale nucleo naturale e fondamentale della società. Il diritto a farsi accompagnare o a ricongiungersi ai membri della propria famiglia costituisce il presupposto da cui dipende la possibilità per lo straniero di esercitare il proprio diritto alla vita familiare. Il ricongiungimento familiare è ...

  19. 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

  20. Giordano Bruno e il Problema della Modernita

    Directory of Open Access Journals (Sweden)

    Stefano Ulliana

    2005-08-01

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

  1. 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)

  2. 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...

  3. 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.

  4. 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.

  5. Conditional IL-2 gene deletion: consequences for T cell proliferation

    Directory of Open Access Journals (Sweden)

    Kendall A Smith

    2012-05-01

    Full Text Available To explore the role of interleukin-2 (IL-2 in T cell proliferation, and to circumvent the IL-2 deficiency autoimmune syndrome of conventional il2 gene deletion, mice were created to allow conditional il2 gene deletion when treated with the estrogen analogue, tamoxifen (TAM as adults. Splenocytes from four different mouse strains, C57Bl/6 wild type (WT, conventional IL-2 (-/-, TAM-treated Cre recombinase negative (Cre-/IL2fl/fl, and Cre+/IL-2fl/fl (Cre+, were activated with anti-CD3 and anti-CD28, and monitored for CD4+ and CD8+ T cell lymphocyte blastogenesis, aerobic glycolysis, BrdU incorporation into newly synthesized DNA, and CFSE dye dilution to monitor cell division. IL-2 production was monitored by quantitative ELISA and multiple additional cytokines were monitored by protein-bead arrays. Splenocytes from conventional IL-2 (-/- and TAM-treated Cre+ mice resulted in undetectable IL-2 production, so that both strains were IL-2 deficient. As monitored by flow cytometry, activated CD4+ and CD8+ T cells from WT, Cre+ and Cre- mice all underwent blastogenesis, whereas far fewer cells from conventional IL-2 (-/- mice did so. By comparison, only cells from IL-2 sufficient WT and Cre- switched to aerobic glycolysis as evidenced by a drop in media pH. Blastogenesis was mirrored by BrdU incorporation and CFSE dye dilution by CD4+ and CD8+ T cells from WT, Cre+ and Cre- mice, which were all equivalent, while proliferation of cells from conventional IL-2 (-/- mice was compromised. Splenocytes from IL-2 deficient conventional IL-2 (-/- mice produced low or undetectable other γc-chain cytokines (IL-4, IL-7, IL-9, IL-13, IL-15, and IL-21, whereas production of these γc-chain cytokines from IL-2-deficient conditional IL-2 (-/- Cre+ mice were comparable with WT and Cre- mice. These results indicate that CD4+ and CD8+ T cell blastogenesis cannot be attributable to IL-2 alone, but a switch to aerobic glycolysis is attributable to IL-2, and proliferation

  6. 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.

  7. 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)

  8. [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.

  9. IL PIRANDELLISMO DI BUZZATI (Seconda Parte) - AJOL

    African Journals Online (AJOL)

    User

    del “Corriere”, ma al quale vuole confessare una strana storia iniziata all'epoca del suo apprendistato giornalistico. Il flashback, costellato da ..... pirandelliani anche della realtà primitiva della Sicilia, la storia che narra è una storia emblematica di un individuo maledetto, di un essere soggiogato dalle mani di un destino ...

  10. Supervising and leading teams in ILS

    CERN Document Server

    Allan, Barbara

    2013-01-01

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

  11. Il progetto Virgo, Einstein e i computer

    CERN Multimedia

    2003-01-01

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

  12. Clay Shirky, Internet e il collegio invisibile

    Directory of Open Access Journals (Sweden)

    Maria Chiara Pievatolo

    2011-10-01

    Full Text Available Come Internet sta cambiando il nostro modo di pensare? Fra le 172 risposte presentate da Edge, Clay Shirky ne propone una particolarmente interessante per i ricercatori di professione. Internet, scrive Shirky, ha aumentato straordinariamente la capacità espressiva dell’umanità. Ma che una risorsa divenga abbondante, da scarsa che era, è una sfortuna, almeno per chi su [...

  13. Il significato della relatività

    CERN Document Server

    Einstein, Albert

    1955-01-01

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

  14. 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.

  15. Family based association analysis of the IL2 and IL15 genes in allergic disorders

    DEFF Research Database (Denmark)

    Christensen, Ulla; Haagerup, Annette; Binderup, Helle

    2006-01-01

    ) identified in a family based association study of two Danish samples comprising a total of 235 families with allergic diseases. None of the IL15 SNPs showed significant association and the haplotype analysis yielded inconsistent results in the two samples. In contrast, the two IL2 SNPs showed association...... both separately and in haplotypes with several atopic phenotypes, most significantly with IgE-mediated allergy. (single SNP P-value 0.0005 for positive skin prick test, haplotype P-value 0.019 for positive RAST test). To our knowledge, this is the first study reporting association between IL2 and Ig...

  16. 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.

  17. Rappresentare il progetto di interaction Design

    Directory of Open Access Journals (Sweden)

    Michele Zannoni

    2013-03-01

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

  18. Vaghezza e chiarezza: tradurre Il grande Gatsby

    Directory of Open Access Journals (Sweden)

    Franca Cavagnoli

    2014-05-01

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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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...

  10. 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)

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

    Lifescience Database Archive (English)

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

  12. Il primato della libertà politica

    Directory of Open Access Journals (Sweden)

    Brunella Casalini

    2012-11-01

    Full Text Available Casalini ripercorre Politics out of History di Wendy Brown soffermandosi in particolare sul dialogo che Brown intrattiene con il pensiero di Marx, Nietzsche e Freud. L’accento posto sul nesso tra libertà individuale e libertà politica e sulla distinzione tra “moralismo” e “moralità” apre alla problematizzazione del nodo teoria-politica. Alla luce della crisi contemporanea della sinistra americana il ruolo del teorico è quindi quello di introdurre tratti di discontinuità in quel discorso di senso comune che la politica tende invece a cristallizzare. In conclusione, secondo Brown, questo scarto deve essere recepito anche dai Women Studies che, restando ancorati a identità statiche, rischiano di non riuscire a svolgere una necessaria «funzione omeopatica» all’interno dei regimi democratici.

  13. 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.

  14. 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

  15. I processorie Itanium "accelerano" il CERN

    CERN Multimedia

    2001-01-01

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

  16. Il museo della scienza di Villa Farnesina

    Directory of Open Access Journals (Sweden)

    Francesca Salvemini

    2005-02-01

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

  17. 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

  18. 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...

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

    Directory of Open Access Journals (Sweden)

    Nurcan Üçeyler

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

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

    Science.gov (United States)

    Puig, Lluís

    2017-06-01

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

  1. 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.

  2. 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.

  3. La matematica e il calcolatore l'avventura pisana

    CERN Document Server

    Capovani, Milvio

    2004-01-01

    La matematica ha invaso domini regolati dall'autorità e dall'abitudine e li ha radicalmente modificati; il calcolatore guida una profonda rivoluzione nel sistema mondo: la matematica, attraverso il calcolatore, si è diffusa in vari campi del sapere. Questi i temi trattati. La storia delle macchine per il calcolo a Pisa è incastonata in questo scenario.

  4. Il valore dell'eBook

    Directory of Open Access Journals (Sweden)

    Nicola Cavalli

    2013-03-01

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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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...

  12. 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.

  13. 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.

  14. Determinants of IL-6 levels during HIV infection

    DEFF Research Database (Denmark)

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

    2014-01-01

    . MATERIAL AND METHODS: Participants in three international HIV trials (SMART, ESPRIT and SILCAAT) with IL-6 plasma levels measured at baseline were included (N=9864). Factors independently associated with log2-transformed IL-6 level were identified by multivariate linear regression; exponentiated estimates......INTRODUCTION: Elevated IL-6 levels have been linked to increased risk of cardiovascular disease (CVD), cancer and death. Compared to the general population, treated HIV+ persons have 50-100% higher IL-6 levels, but few data on the determinants of IL-6 levels during HIV infection currently exist...

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

    International Nuclear Information System (INIS)

    Jiang Zhonglin

    2003-01-01

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

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

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0517 TITLE: IL-9-Producing Mast Cell Precursors and Food Allergy PRINCIPAL INVESTIGATOR: Dr. Simon P. Hogan PhD...IL-9-Producing Mast Cell Precursors and Food Allergy 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Yui Hsi Wang, Sunil...threatening anaphylaxis. We have identified a novel multi-functional IL-9-producing mucosal mast cells (MMC9s) that produce large amounts of IL-9, IL

  17. The Role of IL-33 in Gut Mucosal Inflammation

    Directory of Open Access Journals (Sweden)

    Luca Pastorelli

    2013-01-01

    Full Text Available Interleukin (IL-33 is a recently identified cytokine belonging to the IL-1 family that is widely expressed throughout the body and has the ability to induce Th2 immune responses. In addition, IL-33 plays a key role in promoting host defenses against parasites through the expansion of a novel population of innate lymphoid cells. In recent years, a growing body of evidence has shown that the proinflammatory properties displayed by IL-33 are detrimental in several experimental models of inflammation; in others, however, IL-33 appears to have protective functions. In 2010, four different research groups consistently described the upregulation of IL-33 in patients with inflammatory bowel disease (IBD. Animal models of IBD were subsequently utilized in order to mechanistically determine the precise role of IL-33 in chronic intestinal inflammation, without, however, reaching conclusive evidence demonstrating whether IL-33 is pathogenic or protective. Indeed, data generated from these studies suggest that IL-33 may possess dichotomous functions, enhancing inflammatory responses on one hand and promoting epithelial integrity on the other. This review focuses on the available data regarding IL-33/ST2 in the physiological and inflammatory states of the gut in order to speculate on the possible roles of this novel IL-1 family member in intestinal inflammation.

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

    Science.gov (United States)

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

    2017-09-01

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

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

    CERN Document Server

    Sironi, Giorgio

    2015-01-01

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

  20. 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

  1. Il volgare e il principe. Politica culturale e questione della lingua alla corte di Cosimo

    Directory of Open Access Journals (Sweden)

    Margherita Quaglino

    2015-09-01

    Full Text Available Il principato di Cosimo I rappresenta un periodo di snodo fondamentale per la questione della lingua italiana. Il contributo ripercorre la bibliografia degli ultimi vent’anni con l’intento di definirne le principali traiettorie e individuarne l’originalità e le prospettive future rispetto agli studi precedenti. Sono esaminati in particolare gli studi relativi all’opera di Benedetto Varchi e Vincenzio Borghini; ai volgarizzamenti di Giovan Battista Gelli e Cosimo Bartoli; alla redazione e all’edizione delle Vite di Vasari e al rapporto tra letterati e artisti nella celebrazione del potere.

  2. Il nuovo volto dell'universo

    CERN Document Server

    Radicati di Brozolo, L A

    1994-01-01

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

  3. Il cavo orale nel paziente obeso

    OpenAIRE

    Faggella, Antonella

    2008-01-01

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

  4. Il rilievo del ponte normanno di Serravalle

    Directory of Open Access Journals (Sweden)

    Fulvio Bernardini

    2015-02-01

    Full Text Available Un ponte normanno che versa in stato di totale abbando no nel contesto unico delle forre laviche ai piedi dell’Etna. Un topog rafo che, nonostante alcune difficoltà logistiche ne effettua il rilievo.An ancient norman bridge in disrepair at the foot of Etna, in Sicily. The project to restore the bridge needed a detailed scale model of the bridge and the surrounding area. The survey proved to be demanding due to the difficult conditions of the area: dense vegetation and steep terrain.

  5. 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.

  6. 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.

  7. 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.

  8. IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice.

    Directory of Open Access Journals (Sweden)

    Polyxeni T Mantani

    Full Text Available IL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any influence on atherosclerosis development in mice.Administration of 1 μg IL-25 per day for one week to atherosclerosis-prone apolipoprotein (apoE deficient mice, had limited effect on the frequency of T cell populations, but resulted in a large expansion of ILC2s in the spleen. The expansion was accompanied by increased levels of anti-phosphorylcholine (PC natural IgM antibodies in plasma and elevated levels of IL-5 in plasma and spleen. Transfer of ILC2s to apoE deficient mice elevated the natural antibody-producing B1a cell population in the spleen. Treatment of apoE/Rag-1 deficient mice with IL-25 was also associated with extensive expansion of splenic ILC2s and increased plasma IL-5, suggesting ILC2s to be the source of IL-5. Administration of IL-25 in IL-5 deficient mice resulted in an expanded ILC2 population, but did not stimulate generation of anti-PC IgM, indicating that IL-5 is not required for ILC2 expansion but for the downstream production of natural antibodies. Additionally, administration of 1 μg IL-25 per day for 4 weeks in apoE deficient mice reduced atherosclerosis in the aorta both during initiation and progression of the disease.The present findings demonstrate that IL-25 has a protective role in atherosclerosis mediated by innate responses, including ILC2 expansion, increased IL-5 secretion, B1a expansion and natural anti-PC IgM generation, rather than adaptive Th2 responses.

  9. 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.

  10. 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.

  11. 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

  12. Introducing an ILS methodology into research reactors

    International Nuclear Information System (INIS)

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

    2003-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Marzieh Soleimany

    2018-03-01

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

  14. 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».

  15. 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.

  16. IL-2 and IL-15 regulate CD154 expression on activated CD4 T cells

    DEFF Research Database (Denmark)

    Skov, S; Bonyhadi, M; Odum, Niels

    2000-01-01

    The cellular and humoral immune system is critically dependent upon CD40-CD154 (CD40 ligand) interactions between CD40 expressed on B cells, macrophages, and dendritic cells, and CD154 expressed primarily on CD4 T cells. Previous studies have shown that CD154 is transiently expressed on CD4 T cells...... after T cell receptor engagement in vitro. However, we found that stimulation of PBLs with maximal CD28 costimulation, using beads coupled to Abs against CD3 and CD28, led to a very prolonged expression of CD154 on CD4 cells (>4 days) that was dependent upon autocrine IL-2 production. Previously...... activated CD4 T cells could respond to IL-2, or the related cytokine IL-15, by de novo CD154 production and expression without requiring an additional signal from CD3 and CD28. These results provide evidence that CD28 costimulation of CD4 T cells, through autocrine IL-2 production, maintains high levels...

  17. Importance of IL-10 and IL-17 cytokines in human asthma as studied ...

    African Journals Online (AJOL)

    McRoy

    by ex vivo-stimulated peripheral blood mononuclear cells (PBMNC) by. ELISA. Hence it would be .... excess water and allowed to dry at 37oC for. 30 minutes. Calculation of .... Figure 3: Mean spot distribution for IL-10 in patients and controls.

  18. 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.

  19. 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.

  20. 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

  1. 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.

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  3. Sex Difference in Link between IL-6 and Stress

    Science.gov (United States)

    Jankord, Ryan; Turk, James R.; Schadt, James C.; Casati, Jennifer; Ganjam, Venkataseshu K.; Price, Elmer M.; Keisler, Duane H.; Laughlin, M. Harold

    2009-01-01

    Inflammation contributes to disease development, and the neuro-immuno-endocrine interface is a potential site of action for inflammatory products like IL-6 to affect health. Although plasma IL-6 can stimulate the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis, the precise role, if any, for IL-6 in the HPA response to non-immunological stressors is unclear. The purpose of this study was to test the hypothesis that IL-6 in the stalk median eminence (SME) can be directly involved in stimulating ACTH secretion in response to acute stress in female swine. This study was undertaken as a result of finding IL-6 localized to the external zone of the stalk median eminence (SME) next to the hypophyseal portal vessels. Results indicate that content of IL-6 in the SME decreases in response to acute stress along with an increase in phosphorylation of STAT3 in the anterior pituitary and a simultaneous increase in plasma concentrations of IL-6 and ACTH. Furthermore, we show that females concomitantly display greater SME content of IL-6 and greater HPA responsiveness to stress, thereby suggesting that IL-6 release from the SME is an integral factor contributing to enhanced stress responsiveness in females. Our results provide evidence for a direct link between IL-6 and ACTH release and reveal a sex difference in this relationship. PMID:17510233

  4. Role of IL-33 in inflammation and disease

    Directory of Open Access Journals (Sweden)

    Miller Ashley M

    2011-08-01

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

  5. 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.

  6. Il disegno gotico di San Giovanni Valdarno

    Directory of Open Access Journals (Sweden)

    Maria Teresa Bartoli

    2017-12-01

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

  7. 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 ...

  8. 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...

  9. [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.

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

    Science.gov (United States)

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

    2017-01-01

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

  11. IL-1 Receptor Antagonist Chimeric Protein: Context-Specific and Inflammation-Restricted Activation

    NARCIS (Netherlands)

    Rider, P.; Carmi, Y.; Yossef, R.; Guttman, O.; Eini, H.; Azam, T.; Dinarello, C.A.; Lewis, E.C.

    2015-01-01

    Both IL-1alpha and IL-1beta are highly inflammatory cytokines mediating a wide spectrum of diseases. A recombinant form of the naturally occurring IL-1R antagonist (IL-1Ra), which blocks IL-1R1, is broadly used to treat autoimmune and autoinflammatory diseases; however, blocking IL-1 increases the

  12. 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

  13. 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)

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

    International Nuclear Information System (INIS)

    Gao Wanqin

    2010-01-01

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

  15. 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...

  16. 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)

  17. 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.

  18. 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.

  19. 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

  20. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ~40 and ~1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed......Interleukin (IL)-6 is chronically elevated in type 2 diabetes but also during exercise. However, the exact metabolic role, and hence the physiological significance, has not been elucidated. The objective of this study was to investigate the in vivo effect of recombinant human (rh) IL-6 on human fat...... before, during, and 2 h after cessation of the infusion. Glucose metabolism was unaffected by rhIL-6. In contrast, rhIL-6 increased systemic fatty acid oxidation approximately twofold after 60 min, and it remained elevated even 2 h after the infusion. The increase in oxidation was followed by an increase...

  1. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ∼40 and ∼1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed......Interleukin (IL)-6 is chronically elevated in type 2 diabetes but also during exercise. However, the exact metabolic role, and hence the physiological significance, has not been elucidated. The objective of this study was to investigate the in vivo effect of recombinant human (rh) IL-6 on human fat...... before, during, and 2 h after cessation of the infusion. Glucose metabolism was unaffected by rhIL-6. In contrast, rhIL-6 increased systemic fatty acid oxidation approximately twofold after 60 min, and it remained elevated even 2 h after the infusion. The increase in oxidation was followed by an increase...

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

    CERN Document Server

    Atkins, Peter

    2004-01-01

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

  3. Il tempo perturbante di uno sguardo

    Directory of Open Access Journals (Sweden)

    Piero Zanini

    2010-06-01

    Full Text Available Nell’autunno del 1973 Pier Paolo Pasolini viene invitato a partecipare ad una rubrica televisiva intitolata Io e …, nella quale intellettuali, poeti, registi, musicisti, scrittori sono chiamati a scegliere e a parlare di un’opera d’arte a cui tengono in modo particolare. Dopo un crescendo di ripensamenti intorno al tema da trattare (una pietra, un muretto, una fontana Pasolini sceglie infine di concentrare la sua attenzione sulla forma della città, a partire da due luoghi tanto a lui familiari quanto tra loro radicalmente diversi: la medievale Orte, la fascista Sabaudia. Il risultato della sua partecipazione alla trasmissione è una sorta di ‘scritto corsaro’ per immagini, Pasolini e… la forma della città1, un documento importante e complesso per comprendere la “sostanza di Pasolini” [Contini, 1988] in quel momento particolare della sua vita che sono i primi anni Settanta.

  4. Il "rex sacrorum" in Africa: testimonianze

    Directory of Open Access Journals (Sweden)

    Chantal GABRIELLI

    2010-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Tonia Mingrone

    2012-01-01

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

  6. 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.

  7. Il rischio tecnologico vantaggi e svantaggi del progresso scientifico

    CERN Document Server

    Lewis, H W

    1995-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-06-14

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-07-19

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

  10. 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.

  11. Promoter Variation and Expression Levels of Inflammatory Genes IL1A, IL1B, IL6 and TNF in Blood of Spinocerebellar Ataxia Type 3 (SCA3) Patients.

    Science.gov (United States)

    Raposo, Mafalda; Bettencourt, Conceição; Ramos, Amanda; Kazachkova, Nadiya; Vasconcelos, João; Kay, Teresa; Bruges-Armas, Jácome; Lima, Manuela

    2017-03-01

    Age at onset in spinocerebellar ataxia type 3 (SCA3/MJD) is incompletely explained by the size of the CAG tract at the ATXN3 gene, implying the existence of genetic modifiers. A role of inflammation in SCA3 has been postulated, involving altered cytokines levels; promoter variants leading to alterations in cytokines expression could influence onset. Using blood from 86 SCA3 patients and 106 controls, this work aimed to analyse promoter variation of four cytokines (IL1A, IL1B, IL6 and TNF) and to investigate the association between variants detected and their transcript levels, evaluated by quantitative PCR. Moreover, the effect of APOE isoforms, known to modulate cytokines, was investigated. Correlations between cytokine variants and onset were tested; the cumulative modifier effects of cytokines and APOE were analysed. Patients carrying the IL6*C allele had a significant earlier onset (4 years in average) than patients carrying the G allele, in agreement with lower mRNA levels produced by IL6*C carriers. The presence of APOE*ɛ2 allele seems to anticipate onset in average 10 years in patients carrying the IL6*C allele; a larger number of patients will be needed to confirm this result. These results highlight the pertinence of conducting further research on the role of cytokines as SCA3 modulators, pointing to the presence of shared mechanisms involving IL6 and APOE.

  12. 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

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

    Science.gov (United States)

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

    1996-04-18

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

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

    Directory of Open Access Journals (Sweden)

    Ornella Tajani

    2013-06-01

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

  15. IL-12 Inhibits Lipopolysaccharide Stimulated Osteoclastogenesis in Mice

    Directory of Open Access Journals (Sweden)

    Masako Yoshimatsu

    2015-01-01

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

  16. Poststroke Neuropsychiatric Symptoms: Relationships with IL-17 and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    W. Swardfager

    2014-01-01

    Full Text Available Stroke variably activates interleukin- (IL- 17 expression, reduces regulatory T cells, and induces oxidative stress, which may support neurodegeneration. Ischemic stroke patients were screened for depressive symptoms (Center for Epidemiological Studies Depression (CES-D and cognitive status (Mini Mental State Examination. Proinflammatory cytokines (IL-17, IL-23, and interferon- [IFN-] γ, anti-inflammatory cytokine IL-10, and lipid hydroperoxide (LPH, a measure of oxidative stress, were assayed from fasting serum. Of 47 subjects (age 71.8 ± 14.4 years, 36% female, 19 had depressive symptoms (CES-D ≥ 16, which was associated with poorer cognitive status (F1,46=8.44, P=0.006. IL-17 concentrations did not differ between subjects with and without depressive symptoms (F1,46=8.44, P=0.572; however, IL-17 was associated with poorer cognitive status in subjects with depressive symptoms (F1,46=9.29, P=0.004. In those subjects with depressive symptoms, IL-17 was associated with higher LPH (ρ=0.518, P=0.023 and lower IL-10 (ρ=-0.484, P=0.036, but not in those without. In conclusion, poststroke depressive symptoms may be associated with cognitive vulnerability to IL-17 related pathways, involving an imbalance between proinflammatory and anti-inflammatory activity and increased oxidative stress.

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

    Directory of Open Access Journals (Sweden)

    Maria Ranieri

    2013-03-01

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

  18. The Role of IL-17 in Vitiligo: A Review

    Science.gov (United States)

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

    2016-01-01

    IL-17 is involved in the pathogenesis of several autoimmune diseases, however its role in vitiligo has not been well defined. Emerging human and mouse studies have demonstrated that systemic, tissue, and cellular levels of IL-17 are elevated in vitiligo. Many studies have also shown significant positive correlations between these levels and disease activity, extent, and severity. Treatments that improve vitiligo, such as ultraviolet B phototherapy, also modulate IL-17 levels. This review synthesizes our current understanding of how IL-17 may influence the pathogenesis of autoimmune vitiligo at the molecular level. This has implications for defining new vitiligo biomarkers and treatments. PMID:26804758

  19. Il romanzo paterno in adolescenza: Laio dimenticato dalla psicoanalisi

    Directory of Open Access Journals (Sweden)

    Arturo Casoni

    2015-12-01

    Full Text Available Il Complesso di Edipo ha ricevuto dal movimento psicoanalitico, sempre o quasi, una declinazione che sceglieva come attori principali il figlio maschio e la madre, con l’intervento successivo del padre. Si è così costruita una sorta di mitologia eterosessuale di quel triangolo, lasciando aperto il lato che collega il figlio al padre. Si tenta qui di saldare la parte mancante, a partire dalla narrazione del mito e arrivando alle dinamiche psichiche che caratterizzano le famiglie contemporanee, con particolare attenzione alla clinica dell’adolescenza contemporanea. 

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

    Science.gov (United States)

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

    2016-04-01

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

  1. Quantitative ligand and receptor binding studies reveal the mechanism of interleukin-36 (IL-36) pathway activation.

    Science.gov (United States)

    Zhou, Li; Todorovic, Viktor; Kakavas, Steve; Sielaff, Bernhard; Medina, Limary; Wang, Leyu; Sadhukhan, Ramkrishna; Stockmann, Henning; Richardson, Paul L; DiGiammarino, Enrico; Sun, Chaohong; Scott, Victoria

    2018-01-12

    IL-36 cytokines signal through the IL-36 receptor (IL-36R) and a shared subunit, IL-1RAcP (IL-1 receptor accessory protein). The activation mechanism for the IL-36 pathway is proposed to be similar to that of IL-1 in that an IL-36R agonist (IL-36α, IL-36β, or IL-36γ) forms a binary complex with IL-36R, which then recruits IL-1RAcP. Recent studies have shown that IL-36R interacts with IL-1RAcP even in the absence of an agonist. To elucidate the IL-36 activation mechanism, we considered all possible binding events for IL-36 ligands/receptors and examined these events in direct binding assays. Our results indicated that the agonists bind the IL-36R extracellular domain with micromolar affinity but do not detectably bind IL-1RAcP. Using surface plasmon resonance (SPR), we found that IL-1RAcP also does not bind IL-36R when no agonist is present. In the presence of IL-36α, however, IL-1RAcP bound IL-36R strongly. These results suggested that the main pathway to the IL-36R·IL-36α·IL-1RAcP ternary complex is through the IL-36R·IL-36α binary complex, which recruits IL-1RAcP. We could not measure the binding affinity of IL-36R to IL-1RAcP directly, so we engineered a fragment crystallizable-linked construct to induce IL-36R·IL-1RAcP heterodimerization and predicted the binding affinity during a complete thermodynamic cycle to be 74 μm The SPR analysis also indicated that the IL-36R antagonist IL-36Ra binds IL-36R with higher affinity and a much slower off rate than the IL-36R agonists, shedding light on IL-36 pathway inhibition. Our results reveal the landscape of IL-36 ligand and receptor interactions, improving our understanding of IL-36 pathway activation and inhibition. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-10-09

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

  3. 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)

  4. Altered promoter methylation of PDK4, IL1 B, IL6, and TNF after Roux-en Y gastric bypass

    DEFF Research Database (Denmark)

    Kirchner, Henriette; Nylen, Carolina; Laber, Samantha

    2014-01-01

    methylation of selected promoter regions was measured in whole blood before and after VLCD. A subgroup of seven patients was studied 1–2 days and 12± 3 months after RYGB. Promoter methylation was measured using methylated DNA capture and quantitative real-time polymerase chain reaction (PCR). Results VLCD....... The objective of this study was to test whether promoter methylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1 A), pyruvate dehydrogenase kinase isozyme-4 (PDK4), transcription factor A (TFAM), interleukin-1 beta (IL1 B), interleukin-6 (IL6) and tumor necrosis factor...... decreased promoter methylation of PPARGC1 A. Methylation of PPARGC1 A, TFAM, IL1 B, IL6, and TNF promoters was changed two days after RYGB. Similar changes were also seen on day one after cholecystectomy. Moreover, methylation increased in PDK4, IL1 B, IL6, and TNF promoters 12 months after RYGB. Conclusion...

  5. 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

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

    Directory of Open Access Journals (Sweden)

    Massimiliano Lo Turco

    2015-12-01

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

  7. 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.

  8. IL17/IL17RA as a Novel Signaling Axis Driving Mesenchymal Stem Cell Therapeutic Function in Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Mónica Kurte

    2018-04-01

    Full Text Available The therapeutic effect of mesenchymal stem cells (MSCs in multiple sclerosis (MS and the experimental autoimmune encephalomyelitis (EAE model has been well described. This effect is, in part, mediated through the inhibition of IL17-producing cells and the generation of regulatory T cells. While proinflammatory cytokines such as IFNγ, TNFα, and IL1β have been shown to enhance MSCs immunosuppressive function, the role of IL17 remains poorly elucidated. The aim of this study was, therefore, to investigate the role of the IL17/IL17R pathway on MSCs immunoregulatory effects focusing on Th17 cell generation in vitro and on Th17-mediated EAE pathogenesis in vivo. In vitro, we showed that the immunosuppressive effect of MSCs on Th17 cell proliferation and differentiation is partially dependent on IL17RA expression. This was associated with a reduced expression level of MSCs immunosuppressive mediators such as VCAM1, ICAM1, and PD-L1 in IL17RA−/− MSCs as compared to wild-type (WT MSCs. In the EAE model, we demonstrated that while WT MSCs significantly reduced the clinical scores of the disease, IL17RA−/− MSCs injected mice exhibited a clinical worsening of the disease. The disability of IL17RA−/− MSCs to reduce the progression of the disease paralleled the inability of these cells to reduce the frequency of Th17 cells in the draining lymph node of the mice as compared to WT MSCs. Moreover, we showed that the therapeutic effect of MSCs was correlated with the generation of classical Treg bearing the CD4+CD25+Foxp3+ signature in an IL17RA-dependent manner. Our findings reveal a novel role of IL17RA on MSCs immunosuppressive and therapeutic potential in EAE and suggest that the modulation of IL17RA in MSCs could represent a novel method to enhance their therapeutic effect in MS.

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

    OpenAIRE

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

    2017-01-01

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

  10. 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. 

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Serena Naim

    2013-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Lisa Shen

    2014-07-01

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

  14. 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.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Rebecca L Schmidt

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

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Seifi S, Mokhtari A

    2008-07-01

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

  19. IL-33 activates tumor stroma to promote intestinal polyposis.

    Science.gov (United States)

    Maywald, Rebecca L; Doerner, Stephanie K; Pastorelli, Luca; De Salvo, Carlo; Benton, Susan M; Dawson, Emily P; Lanza, Denise G; Berger, Nathan A; Markowitz, Sanford D; Lenz, Heinz-Josef; Nadeau, Joseph H; Pizarro, Theresa T; Heaney, Jason D

    2015-05-12

    Tumor epithelial cells develop within a microenvironment consisting of extracellular matrix, growth factors, and cytokines produced by nonepithelial stromal cells. In response to paracrine signals from tumor epithelia, stromal cells modify the microenvironment to promote tumor growth and metastasis. Here, we identify interleukin 33 (IL-33) as a regulator of tumor stromal cell activation and mediator of intestinal polyposis. In human colorectal cancer, IL-33 expression was induced in the tumor epithelium of adenomas and carcinomas, and expression of the IL-33 receptor, IL1RL1 (also referred to as IL1-R4 or ST2), localized predominantly to the stroma of adenoma and both the stroma and epithelium of carcinoma. Genetic and antibody abrogation of responsiveness to IL-33 in the Apc(Min/+) mouse model of intestinal tumorigenesis inhibited proliferation, induced apoptosis, and suppressed angiogenesis in adenomatous polyps, which reduced both tumor number and size. Similar to human adenomas, IL-33 expression localized to tumor epithelial cells and expression of IL1RL1 associated with two stromal cell types, subepithelial myofibroblasts and mast cells, in Apc(Min/+) polyps. In vitro, IL-33 stimulation of human subepithelial myofibroblasts induced the expression of extracellular matrix components and growth factors associated with intestinal tumor progression. IL-33 deficiency reduced mast cell accumulation in Apc(Min/+) polyps and suppressed the expression of mast cell-derived proteases and cytokines known to promote polyposis. Based on these findings, we propose that IL-33 derived from the tumor epithelium promotes polyposis through the coordinated activation of stromal cells and the formation of a protumorigenic microenvironment.

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

    International Nuclear Information System (INIS)

    Xue Hongfeng

    2006-01-01

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

  1. 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...

  2. Il rifiuto / Le refus / The refusal

    Directory of Open Access Journals (Sweden)

    Dominici M. R.

    2010-12-01

    Full Text Available L’articolo parte dalla problematica legata alla complessità dei flussi migratori, che vengono esaminati da diversi punti di vista: da un lato, viene evidenziato il tentativo di sottrarsi, da parte di molte persone, a situazioni ambientali di difficoltà, di sofferenza e di miseria ; dall’altro lato, si sottolinea come tale fenomeno possa essere collegato strettamente alla criminalità transnazionale.In entrambe le prospettive, si generano situazioni e rischi di vittimizzazione.Successivamente, prendendo a prestito vecchie favole, vi si costruiscono attorno le esperienze di situazioni reali che riguardano un bambino, il senso e la perdità di identità.Cet article aborde le problème de la complexité des flux migratoires. Ces derniers sont observés selon différents points de vue : d’une part, l’auter met en évidence que de nombreuses personnes essaient d’échapper à des situations éprouvantes, de souffrance et de misère ; d’autre part, l’auter souligne que ce phénomène peut être strictement lié à la criminalité transnationale.Dans les deux cas, des risques de victimisation se créent.Ensuite, en empruntant de vieilles fables, l’auter construit autour d’elles les expériences de vie réelle qui incluent un enfant, le sens et la perte d’identité. This article discusses the problem related to the complexity of migration from different points of view : on the one hand, the author underlines that a large number of people seeks to escape from difficult situations of poverty ; on the other hand, the author highlights that this phenomenon can be strictly related to transnational crime. In both cases, these situations increase the risks of victimization. Then, borrowing old fables, the author builds around them some experiences of real life including the ones of a child and of the sense and the loss of identity.

  3. 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.

  4. Information Literacy (IL) learning experiences: A literature review ...

    African Journals Online (AJOL)

    This paper is a review of extant literature on information literacy. The study reports literature on IL learning experiences in institutions across the globe. It also discusses the spectrum of literacy to give information literacy a context. Furthermore, the paper presents an overview of IL learning initiatives in academic ...

  5. Role of IL-1beta in type 2 diabetes

    DEFF Research Database (Denmark)

    Dinarello, Charles A; Donath, Marc Y; Mandrup-Poulsen, Thomas

    2010-01-01

    To understand the role of inflammation as the fundamental cause of type 2 diabetes and specifically to examine the contribution of IL-1beta.......To understand the role of inflammation as the fundamental cause of type 2 diabetes and specifically to examine the contribution of IL-1beta....

  6. Il marketing budget nel settore bancario e assicurativo.

    OpenAIRE

    Antonella Caru'; Federica Ielasi; Luciano Munari

    2012-01-01

    Il capitolo descrive i risultati della ricerca relativi alle modalità con cui le istituzioni bancarie e assicurative definiscono il budget e l'allocazione dei costi relativi alle attività di marketing; l'analisi evidenzia alcune differenze tra i comportamenti di assicurazioni e banche e, all'interno di queste ultime, tra diverse categorie di banche.

  7. IL-12p35 Inhibits Neuroinflammation and Ameliorates Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Jin Kyeong Choi

    2017-10-01

    Full Text Available Multiple sclerosis (MS is an inflammatory demyelinating disease in which cytokines produced by immune cells that infiltrate the brain and spinal cord play a central role. We show here that the IL-12p35, the alpha subunit of IL-12 or IL-35 cytokine, might be an effective biologic for suppressing neuroinflammatory responses and ameliorating the pathology of experimental autoimmune encephalomyelitis (EAE, the mouse model of human MS. We further show that IL-12p35 conferred protection from neuropathy by inhibiting the expansion of pathogenic Th17 and Th1 cells and inhibiting trafficking of inflammatory cells into the brain and spinal cord. In addition, in vitro exposure of encephalitogenic cells to IL-12p35 suppressed their capacity to induce EAE by adoptive transfer. Importantly, the IL-12p35-mediated expansion of Treg and Breg cells and its amelioration of EAE correlated with inhibition of cytokine-induced activation of STAT1/STAT3 pathways. Moreover, IL-12p35 inhibited lymphocyte proliferation by suppressing the expressions of cell-cycle regulatory proteins. Taken together, these results suggest that IL-12p35 can be exploited as a novel biologic for treating central nervous system autoimmune diseases and offers the promise of ex vivo production of large amounts of Tregs and Bregs for immunotherapy.

  8. Kaempferol impedes IL-32-induced monocyte-macrophage differentiation.

    Science.gov (United States)

    Nam, Sun-Young; Jeong, Hyun-Ja; Kim, Hyung-Min

    2017-08-25

    Kaempferol possesses a wide range of therapeutic properties, including antioxidant, anti-inflammatory, and anticancer properties. The present study sought to evaluate the effects and possible pharmacological mechanisms of kaempferol on interleukin (IL)-32-induced monocyte-macrophage differentiation. In this study, we performed flow cytometry assay, immunocytochemical staining, quantitative real-time PCR, enzyme-linked immuno sorbent assay, caspase-1 assay, and Western blotting to observe the effects and underlying mechanisms of kaempferol using the human monocyte cell line THP-1. The flow cytometry, immunocytochemical staining, and real-time PCR results show that kaempferol attenuated IL-32-induced monocyte differentiation to product macrophage-like cells. Kaempferol decreased the production and mRNA expression of pro-inflammatory cytokines, in this case thymic stromal lymphopoietin (TSLP), IL-1β, tumor necrosis factor (TNF)-α, and IL-8. Furthermore, kaempferol inhibited the IL-32-induced activation of p38 and nuclear factor-κB in a dose-dependent manner in THP-1 cells. Kaempferol also ameliorated the lipopolysaccharide-induced production of the inflammatory mediators TSLP, IL-1β, TNF-α, IL-8, and nitric oxide of macrophage-like cells differentiated by IL-32. In brief, our findings may provide new mechanistic insights into the anti-inflammatory effects of kaempferol. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Integrated Library System (ILS): An Option for Library and ...

    African Journals Online (AJOL)

    The purpose of this paper is to review the capability of integrated library system as an option for managing library information resources using Koha ILS used at Babcock University as a case study. The paper is a review of the functions and performance of Koha ILS. It also includes personal experiences of librarians and the ...

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

    African Journals Online (AJOL)

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

  11. IL-33 and Thymic Stromal Lymphopoietin in mast cell functions

    NARCIS (Netherlands)

    Saluja, Rohit; Zoltowska, Anna; Ketelaar, Maria Elizabeth; Nilsson, Gunnar

    2016-01-01

    Thymic Stromal Lymphopoietin (TSLP) and Interleukin 33 (IL-33) are two cytokines released by cells that are in proximity to our environment, e.g., keratinocytes of the skin and epithelial cells of the airways. Pathogens, allergens, chemicals and other agents induce the release of TSLP and IL-33,

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. [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.

  20. Il movimento degli scioperi nel XX secolo

    Directory of Open Access Journals (Sweden)

    Maria Theresa Schorer Petrone

    1983-06-01

    Full Text Available Cella, Gian Primo (organizador. Il movimento degli scioperi nel XX secolo. Bologna, Società Editrice Mulino, 1979. (primeiro parágrado do texto "O movimento das greves no século XX" constitui o resultado de laboriosa pesquisa realizada por um grupo de sociólogos— Guido 13oglioni, Lorenzo Bordogna, Gian Primo Cella, Pietro Kemeny, Giancarlo Provasi, Guido Romagnoli e Gian Enrico Rusconi — ligados às universidades de Turim, Parma, Trento e Cagliari.  Analisando com técnicas de quantificação, os mais variados aspectos das greves ocorridas desde o início deste século até 1970 na Grã Bretanha, Alemanha, Itália, França e nos Estados Unidos, e considerando esses niovimentos' os indicadores mais significativos da ação operária enquanto Manifestação sindical e reinvindicativa, acreditavam que poderiam de-teCtar as relações entre ação operária e as 'mudanças sociais.  O livro em questão é o resultado da primeira fase desta pesquisa em que se procurou reconstruir os movimentos grevistas e suas formas, chegando-se a construir modelos explicativos .

  1. Changes of serum IL-2, IL-4, IL-10 and IFN-γ levels after treatment with 131I-17-allylamino-17-demethoxygeldanamycin in VX2 rabbit models

    International Nuclear Information System (INIS)

    Gao Wen; Liu Lu; Zhou Yun

    2007-01-01

    Objective: To study the influence of 131 I-17-allylamino-17-demethoxygeldanamycin( 131 I-17-AAG) therapy on immune function in VX2 rabbit models with transplanted liver cancer. Methods: Serum IL-2, IL-4, IL-10 and IFN-γ levels were measured with RIA in 8 VX2 rabbit models with transplanted liver cancer 1-2 weeks after 10mCi 131 I-17-AAG treatment as well as in 8 controls rabbits (models with tumor but without treatment). Results: 1 week after 10mCi 131 I treatment, the serum IL - 2 and IFN-γ levels were significantly lower in the treated rabbits than those in controls (P 0.05). Serum IL-4 and IL-10 levels in the treated rabbits (both at 1 and 2 week) were not significantly different from those in controls (P>0.05). Conclusion: 131 I-17-AAG treatment had transient effects on cellular immunity with no influence on humoral immunity. As a whole, it is a safe to treat VX2 rabbit models with this preparation. (authors)

  2. Il mondo dei quanti la fisica quantistica per tutti

    CERN Document Server

    Ford, Kenneth W

    2006-01-01

    L'autore spiega come le leggi che governano l'enormemente piccolo e l'enormemente rapido sfidino il senso comune e mettano alla prova l'intelletto al limite delle sue possibilità. Ford introduce alle grandi idee di una teoria - la fisica quantistica - che continua a rimanere misteriosa nonostante i numerosi successi: la granularità (la materia e alcune sue proprietà, come l'energia, sono "grumose"), il dualismo onda-particella, il principio di indeterminazione, la natura dei bosoni e dei fermioni, il principio di sovrapposizione e la non separabilità (il fatto che un atomo possa trovarsi simultaneamente in due o più stati di moto diversi).

  3. IL6 gene promoter polymorphisms and type 2 diabetes

    DEFF Research Database (Denmark)

    Huth, Cornelia; Heid, Iris M; Vollmert, Caren

    2006-01-01

    Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, -174G>C (rs1800795) and -573G>C (rs1800796), have been investigated for association with type...... 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on >20,000 participants from 21 published and unpublished studies. Collected data represent eight different...... countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 -174G>C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found...

  4. IL-17/Th17 Pathway Is Activated in Acne Lesions

    Science.gov (United States)

    Kelhälä, Hanna-Leena; Palatsi, Riitta; Fyhrquist, Nanna; Lehtimäki, Sari; Väyrynen, Juha P.; Kallioinen, Matti; Kubin, Minna E.; Greco, Dario; Tasanen, Kaisa; Alenius, Harri; Bertino, Beatrice; Carlavan, Isabelle; Mehul, Bruno; Déret, Sophie; Reiniche, Pascale; Martel, Philippe; Marty, Carine; Blume-Peytavi, Ulrike; Voegel, Johannes J.; Lauerma, Antti

    2014-01-01

    The mechanisms of inflammation in acne are currently subject of intense investigation. This study focused on the activation of adaptive and innate immunity in clinically early visible inflamed acne lesions and was performed in two independent patient populations. Biopsies were collected from lesional and non-lesional skin of acne patients. Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed at the RNA and also protein level with real-time PCR (RT-PCR) and Luminex technology. Cytokines involved in Th17 lineage differentiation (IL-1β, IL-6, TGF-β, IL23p19) were remarkably induced at the RNA level. In addition, proinflammatory cytokines and chemokines (TNF-α, IL-8, CSF2 and CCL20), Th1 markers (IL12p40, CXCR3, T-bet, IFN-γ), T regulatory cell markers (Foxp3, IL-10, TGF-β) and IL-17 related antimicrobial peptides (S100A7, S100A9, lipocalin, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL-17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway is activated and may play a pivotal role in the disease process, possibly offering new targets of therapy. PMID:25153527

  5. 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.

  6. The modulatory role of cytokines IL-4 and IL-17 in the functional activity of phagocytes in diabetic pregnant women.

    Science.gov (United States)

    Fagundes, Danny L G; França, Eduardo L; Gonzatti, Michelangelo B; Rugde, Marilza V C; Calderon, Iracema M P; Honorio-França, Adenilda C

    2018-01-01

    The study investigated the role of cytokines IL-4 and IL-17 in the modulation of the functional activity of mononuclear phagocytes in diabetic pregnant women with hyperglycemia. Sixty pregnant women were assigned to the following groups: nondiabetic (ND), mild gestational hyperglycemia (MGH), gestational diabetes mellitus (GDM), or type 2 diabetes mellitus (DM2). The functional activity of phagocytes from maternal blood, cord blood, and colostrum was assessed by determining their superoxide release, phagocytosis, microbicidal activity, and intracellular Ca 2+ release. Irrespective of glycemic status, colostrum and blood cells treated with IL-4 and IL-17 increased superoxide release in the presence of enteropathogenic Escherichia coli (EPEC). The highest phagocytosis rate was observed in cells from the DM2 group treated with IL-4. In all the groups, phagocytes from colostrum, maternal blood, and cord blood exhibited higher microbicidal activity against EPEC when treated with cytokines. IL-17 increased intracellular Ca 2+ release by colostrum phagocytes in diabetic groups. The results indicate that the IL-4 and IL-17 modulate the functional activity of phagocytes in the maternal blood, cord blood, and colostrum of diabetic mother. The natural immunity resulting from the interaction between the cells and cytokines tested may be an alternative procedure to improve the prognosis of maternal and newborn infections. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  7. 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.

  8. Genetic deletion of IL-25 (IL-17E) confers resistance to dextran sulfate sodium-induced colitis in mice

    Science.gov (United States)

    IL-25 is emerging as a key regulator of inflammation in the intestinal mucosa because of its ability to promote Th2 while suppressing Th1 and Th17 cytokine responses. We investigated the contribution of endogenous IL-25 to DSS-induced colitis in mice. Mice were exposed to DSS in drinking water ad li...

  9. THE EFFECTS OF IL-1 AND IL-4 ON THE EPO-INDEPENDENT ERYTHROID PROGENITOR IN POLYCYTHEMIA-VERA

    NARCIS (Netherlands)

    DEWOLF, JTM; HENDRIKS, DW; ESSELINK, MT; HALIE, MR; VELLENGA, E

    1994-01-01

    Human recombinant interleukin-1 (IL-1) was studied for its effects on the erythroid progenitors from normal subjects and from patients with polycythaemia vera (PV). No supportive effect of IL-1 was noticed on the normal, erythropoietin (Epo) dependent, erythroid burst-forming unit (BFU-E) using

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    activity of 75 cpm/pg. Validation of the tracer confirmed preserved antibody epitopes and receptor binding ability. A robust Radio Immuno Assay (RIA) was developed and validated to detect natural human anti-IL-10 antibodies based on the formation of (125)I-labeled IL-10-IgG complexes in solution...

  11. Increased IL-35 producing Tregs and CD19+IL-35+ cells are associated with disease progression in leprosy patients.

    Science.gov (United States)

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

    2017-03-01

    The clinical forms of leprosy consist of a spectrum that reflects the host's immune response to the M. leprae; it provides an ideal model to study the host pathogen interaction and immunological dysregulation in humans. IL-10 and TGF-β producing Tregs are high in leprosy patients and responsible for immune suppression and M. leprae specific T cells anergy. In leprosy, involvement of IL-35 producing Tregs and Bregs remain unstudied. To study the role of IL-35 producing Tregs and Bregs in the human leprosy. Peripheral blood mononuclear cells from leprosy patients were isolated and stimulated with M. leprae antigen (MLCwA) for 48h. Intracellular cytokine IL-35 was evaluated in CD4 + CD25 + Tregs, CD19 + cells by FACS. Expression of PD-1 on CD4 + CD25 + Tregs, CD19 + cells and its ligand (PD-L1) on B cells, CD11c cells were evaluated by flow cytometry (FACS). Serum IL-35 level was estimated by ELISA. The frequency of IL-35 producing Tregs and Bregs cells were found to be high in leprosy patients (pleprosy patients. This study point out a shift in our understanding of the immunological features that mediate and regulate the immune suppression and the disease progression in leprosy patients with a new paradigm (IL-35 producing Tregs and Bregs) that is beyond TGF-β and IL-10 producing Treg cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. 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.

  13. 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

  14. Interleukin (IL)-1 in rat parturition: IL-1 receptors 1 and 2 and accessory proteins abundance in pregnant rat uterus at term - regulation by progesterone.

    Science.gov (United States)

    Ishiguro, Tomohito; Takeda, Jun; Fang, Xin; Bronson, Heather; Olson, David M

    2016-07-01

    The role of interleukin-1 (IL-1), a pro-inflammatory cytokine, in parturition is typically noted by changes in its concentrations. Studying the expression of its receptor family, IL-1 receptor (IL-1R) 1, IL-1R2, IL-1R accessory protein (IL-1RAcP), and its predominantly brain isoform, IL-1RAcPb, during late gestation in the uterus in the Long-Evans rat is another. We assessed changes in their mRNA and protein relative abundance in the uterus and compared IL-1RAcP and IL-1RAcPb mRNA abundance in uterus, cervix, ovaries, placenta, and whole blood of Long-Evans rats during late gestation or in RU486 and progesterone-treated dams using quantitative real-time PCR and western immunoblotting. IL-1R1, IL-1RAcP, and IL-1RAcPb mRNA abundance significantly increased in the uterus at delivery whereas IL-1R2 mRNA abundance significantly decreased. IL-1R1 protein increased at term and IL-1R2 protein decreased at term compared to nonpregnant uteri. IL1-RAcPb mRNA abundance was less than IL-1RAcP, but in the lower uterine segment it was the highest of all tissues examined. RU486 stimulated preterm delivery and an increase in IL-1R1 mRNA abundance whereas progesterone administration extended pregnancy and suppressed the increase in IL-1R1. These data suggest that changes in uterine sensitivity to IL-1 occur during late gestation and suggest another level of regulation for the control of delivery. The roles for IL-1RAcP and IL-1RAcPb need to be determined, but may relate to different intracellular signaling pathways. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  15. 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

  16. A state of acquired IL-10 deficiency in 0.4% of Danish blood donors

    DEFF Research Database (Denmark)

    de Lemos Rieper, Carina; Galle, Pia; Pedersen, Bente Klarlund

    2010-01-01

    Autoantibodies against a variety of growth factors and cytokines are present in preparations of pooled normal human IgG, such as IVIg. The present study demonstrated that healthy Danish blood donors produced high concentrations of anti-IL-10 IgG antibodies that bound IL-10 with extremely high...... in highly diluted plasma samples, providing the explanation for the fact that relatively low antibody activity can be detected in normal human pooled IgG, derived from the plasma of over 1000 blood donors....... family (IL-19, IL-20, IL-22, IL-24, IL-26, IL-28A, IL-28B, IL-29). The production of anti-IL-10 antibodies was stable from months to years, and high positive donors were likely to acquire a state of IL-10 deficiency in the circulation during this period. Anti-IL-10 antibodies were readily measurable even...

  17. Antibody blockade of IL-17 family cytokines in immunity to acute murine oral mucosal candidiasis.

    Science.gov (United States)

    Whibley, Natasha; Tritto, Elaine; Traggiai, Elisabetta; Kolbinger, Frank; Moulin, Pierre; Brees, Dominique; Coleman, Bianca M; Mamo, Anna J; Garg, Abhishek V; Jaycox, Jillian R; Siebenlist, Ulrich; Kammüller, Michael; Gaffen, Sarah L

    2016-06-01

    Antibodies targeting IL-17A or its receptor, IL-17RA, are approved to treat psoriasis and are being evaluated for other autoimmune conditions. Conversely, IL-17 signaling is critical for immunity to opportunistic mucosal infections caused by the commensal fungus Candida albicans, as mice and humans lacking the IL-17R experience chronic mucosal candidiasis. IL-17A, IL-17F, and IL-17AF bind the IL-17RA-IL-17RC heterodimeric complex and deliver qualitatively similar signals through the adaptor Act1. Here, we used a mouse model of acute oropharyngeal candidiasis to assess the impact of blocking IL-17 family cytokines compared with specific IL-17 cytokine gene knockout mice. Anti-IL-17A antibodies, which neutralize IL-17A and IL-17AF, caused elevated oral fungal loads, whereas anti-IL-17AF and anti-IL-17F antibodies did not. Notably, there was a cooperative effect of blocking IL-17A, IL-17AF, and IL-17F together. Termination of anti-IL-17A treatment was associated with rapid C. albicans clearance. IL-17F-deficient mice were fully resistant to oropharyngeal candidiasis, consistent with antibody blockade. However, IL-17A-deficient mice had lower fungal burdens than anti-IL-17A-treated mice. Act1-deficient mice were much more susceptible to oropharyngeal candidiasis than anti-IL-17A antibody-treated mice, yet anti-IL-17A and anti-IL-17RA treatment caused equivalent susceptibilities. Based on microarray analyses of the oral mucosa during infection, only a limited number of genes were associated with oropharyngeal candidiasis susceptibility. In sum, we conclude that IL-17A is the main cytokine mediator of immunity in murine oropharyngeal candidiasis, but a cooperative relationship among IL-17A, IL-17AF, and IL-17F exists in vivo. Susceptibility displays the following hierarchy: IL-17RA- or Act1-deficiency > anti-IL-17A + anti-IL-17F antibodies > anti-IL-17A or anti-IL-17RA antibodies > IL-17A deficiency. © Society for Leukocyte Biology.

  18. Il danese tranquillo Niels Bohr, un fisico e il suo tempo, 1885-1962

    CERN Document Server

    Pais, Abraham

    1993-01-01

    Niels Bohr è una figura centrale nella fisica del Novecento, padre fondatore della teoria atomica e della meccanica quantistica. La storia della sua vita, ricca e piena anche sul piano affettivo e personale, non può dunque ridursi a un resoconto dei suoi successi scientifici e Pais, allievo e poi amico di Bohr, ne è perfettamente consapevole. Il libro si sviluppa su vari piani: capitoli strettamente biografici o storico-scientifici si alternano a discussioni sulle idee di Bohr in campo politico e filosofico, sui suoi rapporti con Einstein, sul suo ruolo nei drammatici anni della guerra e su molti altri aspetti della vicenda umana.

  19. Il fantasma dell'universo che cos'è il neutrino

    CERN Document Server

    Votano, Lucia

    2015-01-01

    Ben prima della luce, a un decimillesimo di secondo dal Big Bang, i neutrini sono apparsi nell'universo. Dopo un secondo il brodo primordiale si era raffreddato abbastanza da consentire loro di muoversi liberi e ancora oggi, dopo quasi quattordici miliardi di anni, sono numerosissimi. Ma che cosa sono i neutrini? Elusivi come fantasmi, camaleontici, viaggiano indenni attraverso la materia arrivando dritti sino a noi dagli angoli più remoti e nascosti dell'universo. Per saperne di più seguiremo i fisici che li studiano in laboratori sotterranei o in luoghi estremi come i ghiacciai polari o le profondità marine.

  20. La camorra e il caso Cirillo

    Directory of Open Access Journals (Sweden)

    A cura di Sarah Mazzenzana

    2016-11-01

    Full Text Available La sezione “Storia e Memoria” offre una selezione di brani tratti dal “Rapporto sulla Camorra” redatto dalla Commissione Parlamentare Antimafia nel 1993. Per la prima volta nella storia la Commissione rivolge la sua attenzione specificamente alla Camorra, fenomeno criminale fino a quel momento sottovalutato. Pubblichiamo qui la terza parte del rapporto, la quale offre uno spaccato degli eventi che hanno permesso la crescita imprenditoriale della Camorra: la ricostruzione delle aree colpite dal terremoto dell’Irpinia del 1980, l’ascesa della Nuova Camorra Organizzata di Raffaele Cutolo e infine il sequestro dell’allora assessore regionale ai lavori pubblici, Ciro Cirillo, episodio che sconvolse la politica e le istituzioni mettendone a nudo le complicità. Parole chiave: camorra; Commissione Parlamentare Antimafia; terremoto; sequestro Cirillo; imprenditoria The section “History and Memory” reports a selection of excerpts from the “Rapporto sulla Camorra”, issued by the Italian Parliamentary Anti-Mafia Commission in 1993. For the first time in its history, the Parliamentary Anti-Mafia Commission drew its attention specifically on a phenomenon which until that moment had been understimated. This document offers a significant  and thorough  understanding of the Camorra by dealing with the historical events that allowed the Campania criminal organisation’s entrepreneurial development, including the building reconstruction of the areas hit by the 1980 Irpinia earthquake , the growth of the Nuova Camorra Organizzata and the kidnapping of politician Ciro Cirillo.  Keywords: camorra; Italian Parliamentary Anti-mafia Commission; earthquake; Cirillo kidnapping; enterprise

  1. The role of IL-1 gene polymorphisms (IL1A, IL1B, and IL1RN) as a risk factor in unsuccessful implants retaining overdentures.

    Science.gov (United States)

    Sampaio Fernandes, Margarida; Vaz, Paula; Braga, Ana Cristina; Sampaio Fernandes, João Carlos; Figueiral, Maria Helena

    2017-10-01

    Implant-supported overdentures are an alternative predictable rehabilitation method that has a high impact on improving the patient's quality of life. However, some biological complications may interfere with the maintenance and survival of these overdenture implants. The goal of this article was to assess the factors that affect peri-implant success, through a hypothetical prediction model for biological complications of implant overdentures. A retrospective observational, prevalence study was conducted in 58 edentulous Caucasian patients rehabilitated with implant overdentures. A total of 229 implants were included in the study. Anamnestic, clinical, and implant-related parameters were collected and recorded in a single database. "Patient" was chosen as the unit of analysis, and a complete screening protocol was established. The data analytical study included assessing the odds ratio, concerning the presence or absence of a particular risk factor, by using binary logistic regression modeling. Probability values (p values) inferior to 0.05 were considered as representing statistically significant evidence. The performed prediction model included the following variables: mean probing depth, metal exposure, IL1B_allele2, maxillary edentulousness, and Fusobacterium nucleatum. The F. nucleatum showed significant association with the outcome. Introducing a negative coefficient appeared to prevent complications or even boost the biological defense when associated with other factors. The prediction model developed in this study could serve as a basis for further improved models that would assist clinicians in the daily diagnosis and treatment planning practice of oral rehabilitation with implant overdentures. Copyright © 2017 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  2. 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.

  3. Genetic regulation ofmethylation and IL1RL1-a protein levels in asthma

    NARCIS (Netherlands)

    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

    2018-01-01

    Interleukin-1 receptor-like 1 (IL1RL1) is an important asthma gene. (Epi)genetic regulation ofIL1RL1protein expression has not been established. We assessed the association betweenIL1RL1single nucleotide polymorphisms (SNPs),IL1RL1methylation and serum IL1RL1-a protein levels, and aimed to identify

  4. IL-1RN gene polymorphism is associated with peri-implantitis

    NARCIS (Netherlands)

    Laine, Marja L.; Leonhardt, Asa; Roos-Jansaker, Ann-Marie; Salvador Pena, A.; van Winkelhoff, Arie Jan; Winkel, Edwin G.; Renvert, Stefan

    Objectives: Interleukin (IL)-1 alpha, IL-1 beta and their natural specific inhibitor IL-1 receptor antagonist (IL-1ra) play a key role in the regulation of the inflammatory response in periodontal tissues. Polymorphisms in the IL-1 gene cluster have been associated with severe adult periodontitis.

  5. Beneficial effects of IL-37 after spinal cord injury in mice

    NARCIS (Netherlands)

    Coll-Miro, M.; Francos-Quijorna, I.; Santos-Nogueira, E.; Torres-Espin, A.; Bufler, P.; Dinarello, C.A.; Lopez-Vales, R.

    2016-01-01

    IL-37, a member of the IL-1 family, broadly reduces innate inflammation as well as acquired immunity. Whether the antiinflammatory properties of IL-37 extend to the central nervous system remains unknown, however. In the present study, we subjected mice transgenic for human IL-37 (hIL-37tg) and

  6. TNF-α blockade induces IL-10 expression in human CD4+ T cells

    NARCIS (Netherlands)

    Evans, Hayley G.; Roostalu, Urmas; Walter, Gina J.; Gullick, Nicola J.; Frederiksen, Klaus S.; Roberts, Ceri A.; Sumner, Jonathan; Baeten, Dominique L.; Gerwien, Jens G.; Cope, Andrew P.; Geissmann, Frederic; Kirkham, Bruce W.; Taams, Leonie S.

    2014-01-01

    IL-17+ CD4+ T (Th17) cells contribute to the pathogenesis of several human inflammatory diseases. Here we demonstrate that TNF inhibitor (TNFi) drugs induce the anti-inflammatory cytokine IL-10 in CD4+ T cells including IL-17+ CD4+ T cells. TNFi-mediated induction of IL-10 in IL-17+ CD4+ T cells is

  7. Post-stroke infection: a role for IL-1ra?

    Science.gov (United States)

    Tanzi, Pat; Cain, Kevin; Kalil, Angela; Zierath, Dannielle; Savos, Anna; Gee, J Michael; Shibata, Dean; Hadwin, Jessica; Carter, Kelly; Becker, Kyra

    2011-04-01

    Infection is common following stroke and is independently associated with worse outcome. Clinical studies suggest that infections occur more frequently in those individuals with stroke-induced immunologic dysfunction. This study sought to explore the contribution of immunomodulatory cytokines and hormones to lymphocyte function and infection risk. Patients (N = 112) were enrolled as soon as possible after the onset of ischemic stroke. Blood was drawn to assess plasma cortisol, IL-10, IL-1ra, lymphocyte numbers, and lymphocyte function at 72 h after stroke onset; infections were censored through 21 days after stroke onset. Infection occurred in 25% of patients. Stroke severity was the most important predictor of infection risk. Increased plasma cortisol, IL-10, and IL-1ra, as well as decreased lymphocyte numbers, at 72 h after stroke onset were associated with risk of subsequent infection. After controlling for stroke severity, only IL-1ra was independently associated with infection risk, and the degree of risk was consistent throughout the post-stroke period. Infection, but not IL-1ra itself, was associated with worse outcome at 3 months. In this study cohort, increased plasma IL-1ra was independently associated with the risk of post-stroke infection. Further studies are needed to validate this finding, which could have important implications for stroke therapy.

  8. Evolutionary Insights into IL17A in Lagomorphs

    Directory of Open Access Journals (Sweden)

    Fabiana Neves

    2015-01-01

    Full Text Available In leporids, IL17A had been implicated in the host defense against extracellular pathogens, such as Francisella tularensis that infects hares and rabbits and causes the zoonotic disease tularemia. Here, we studied IL17A from five lagomorphs, European rabbit, pygmy rabbit, brush rabbit, European brown hare, and American pika. We observed that this protein is highly conserved between these species, with a similarity of 97–99% in leporids and ~88% between leporids and American pika. The exon/intron structure, N-glycosylation sites, and cysteine residues are conserved between lagomorphs. However, at codon 88, one of the interaction sites between IL17A and its receptor IL17RA, there is an Arg>Pro mutation that only occurs in European rabbit and European brown hare. This could induce critical alterations in the IL17A structure and conformation and consequently modify its function. The differences observed between leporids and humans or rodents might also represent important alterations in protein structure and function. In addition, as for other interleukins, IL17A sequences of human and European rabbit are more closely related than the sequences of human and mouse or European rabbit and mouse. This study gives further support to the hypothesis that European rabbit might be a more suitable animal model for studies on human IL17.

  9. 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

  10. 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

  11. IL-33-induced alterations in murine intestinal function and cytokine responses are MyD88, STAT6, and IL-13-dependent

    Science.gov (United States)

    IL-33 is a recently identified cytokine member of the IL-1 family. The biological activities of IL-33 are associated with promotion of Th2 and inhibition of Th1/Th17 immune responses. Exogenous IL-33 induces a typical “type 2” immune response in the gastrointestinal tract, yet the underlying mechani...

  12. Mutual enhancement of IL-2 and IL-7 on DNA vaccine immunogenicity mainly involves regulations on their receptor expression and receptor-expressing lymphocyte generation.

    Science.gov (United States)

    Zhang, Yonghong; Liang, Shuang; Li, Xiujin; Wang, Liyue; Zhang, Jianlou; Xu, Jian; Huo, Shanshan; Cao, Xuebin; Zhong, Zhenyu; Zhong, Fei

    2015-07-09

    Our previous study showed that IL-2 and IL-7 could mutually enhance the immunogenicity of canine parvovirus VP2 DNA vaccine, although the underlying mechanism remained unknown. Here, we used the OVA gene as a DNA vaccine in a mouse model to test their enhancement on DNA vaccine immunogenicity and to explore the molecular mechanism. Results showed that both IL-2 and IL-7 genes significantly increased the immunogenicity of OVA DNA vaccine in mice. Co-administration of IL-2 and IL-7 genes with OVA DNA significantly increased OVA-specific antibody titers, T cell proliferation and IFN-γ production compared with IL-2 or IL-7 alone, confirming that IL-2 and IL-7 mutually enhanced DNA vaccine immunogenicity. Mechanistically, we have shown that IL-2 significantly stimulated generation of IL-7 receptor-expressing lymphocytes, and that IL-7 significantly induced IL-2 receptor expression. These results contribute to an explanation of the mechanism of the mutual effects of IL-2 and IL-7 on enhancing DNA vaccine immunogenicity and provided a basis for further investigation on their mutual effects on adjuvant activity and immune regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Release of IL-1β via IL-1β-Converting Enzyme in a Skin Dendritic Cell Line Exposed to 2,4-Dinitrofluorobenzene

    Directory of Open Access Journals (Sweden)

    Teresa J. Matos

    2005-01-01

    increased IL-1β receptor immunoreactivity. The rapid effect of DNFB on the release of mature IL-1β, without inducing an increase of IL-1β mRNA in FSDC, suggests a posttranslational modification of pro-IL-1β by ICE activity.

  14. 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.

  15. Characterization of atmospheric aerosol near motor way: Bassa Valle Susa (Italy); Caratterizzazione dell`aerosol atmosferico in prossimita` di un`autostrada: Bassa Valle Susa

    Energy Technology Data Exchange (ETDEWEB)

    Berico, M.; Castellani, C.M.; Formignani, M. [ENEA, Bologna (Italy). Dipt. Ambiente

    1995-10-01

    Results related to the experimental measurement campaign to characterize atmospheric aerosol carried out near Avigliana (Turin) from 18 to 22 October 1994 are presented in this paper. In the frame of the project aimed at evaluating the impact of the mountain motor way A-32 Rivoli-Bardonecchia-Frejus on the Susa Valley environment and on man the present measurement campaign is the second, and last, one envisaged in the project. The sampling place is in the initial part of the Susa Valley while previous measurements were carried out in the high part of it. Mass mean concentrations result greater in the low than in the high part of the valley approximately by a factor of 3. It is not possible to prove a difference between the 3 sampling positions transversely placed from 20 to 80 m. in comparison with the motor way axis. Whereas mass mean concentrations dropped substantially due to atmospheric precipitations during the last two measurement day. Aerosol granulometry in mass for the accumulation and the coarse mode do not differ from that evaluated in the high part of the valley and fitting granulometric parameters are consistent with those previously evaluated.

  16. IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP.

    Directory of Open Access Journals (Sweden)

    Stephen F Murphy

    Full Text Available Chronic pelvic pain syndrome (CPPS is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.

  17. IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP).

    Science.gov (United States)

    Murphy, Stephen F; Schaeffer, Anthony J; Done, Joseph; Wong, Larry; Bell-Cohn, Ashlee; Roman, Kenny; Cashy, John; Ohlhausen, Michelle; Thumbikat, Praveen

    2015-01-01

    Chronic pelvic pain syndrome (CPPS) is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP) in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.

  18. Polymorphisms of ST2-IL18R1-IL18RAP gene cluster: a new risk for autoimmune thyroid diseases.

    Science.gov (United States)

    Wang, X; Zhu, Y F; Li, D M; Qin, Q; Wang, Q; Muhali, F S; Jiang, W J; Zhang, J A

    2016-02-01

    Interleukin 33 (IL33) / ST2 pathway and ST2-interlukin18 receptor1-interlukin18 receptor accessory protein (ST2-IL18R1-IL18RAP) gene cluster have been involved in many autoimmune diseases but few report in autoimmune thyroid diseases (AITD). In this study, we investigated whether polymorphisms of IL33, ST2, IL18R1, and IL18RAP are associated with Graves' disease (GD) and Hashimoto's thyroiditis (HT), two major forms of AITD, among a Chinese population. A total of 11 SNPs were explored in a case-control study including 417 patients with GD, 250 HT patients and 301 controls, including rs1929992, rs10975519, rs10208293, rs6543116, rs1041973, rs3732127, rs11465597, rs1035130, rs2293225, rs1035127, rs917997 of IL 33, ST2-IL18R1-IL18RAP gene cluster. Genotyping of these SNPs was performed using matrix-assisted laser desorption / ionization-time-of-flight mass spectrometer (MALDI-TOF-MS) platform from Sequenom. The frequencies of allele A and AA+AG genotype of rs6543116 (ST2) in HT patients were significantly increased compared with those of the controls (P = 0.029/0.021, OR = 1.31/1.62). And in another SNP rs917997, AA+AG genotype presented an increased frequency in HT subjects compared with controls (P = 0.046, OR = 1.53). Furthermore, the haplotype GAGCCCG from ST2-IL18R1-IL18RAP gene cluster (rs6543116, rs1041973, rs1035130, rs3732127, rs1035127, rs2293225, rs917997) was associated with increased susceptibility to GD with an OR of 2.03 (P = 0.022, 95% CI = 1.07-3.86). Some SNPs of ST2-IL18R1-IL18RAP gene cluster might increase the risk of susceptibility of HT and GD in Chinese Han population. © 2015 John Wiley & Sons Ltd.

  19. Conoscere il patrimonio architettonico: il DARDUS dell’Università Politecnica delle Marche

    Directory of Open Access Journals (Sweden)

    Eva Savina Malinverni

    2007-03-01

    Full Text Available E’ in questa ottica che all’interno del Dipartimento collaborano docenti e ricercatori di vari settori scientificodisciplinari. Nella panoramica che viene qui presentata verrà posto l’accento maggiormente su due filoni di attività che sono anche più inerenti al contesto divulgativo di GEOmedia: il rilievo ed i sistemi informativi. Tematiche sulle quali il gruppo di ricerca del DARDUS ha avviato varie iniziative che verranno di seguito illustrate. Le dinamiche di collaborazione e di ricerca inerenti i temi del rilievo e della documentazione in banche datigeoreferenziate sviluppate nelle sale del Dipartimento riguardano non solo l’ambito architettonico ma anche quello ambientale. Queste attività sono svolte all’interno di laboratori debitamente attrezzati, nei quali docenti, ricercatori e tecnici istruiscono dottorandi, laureandi etirocinanti in stretta collaborazione e produttiva sinergia portando a sviluppare e collaudare nuove procedure e sistemi integrati di acquisizione e gestione dei dati raccoltinella varie esperienze di studio.

  20. Nuove prospettive di ricerca: il 'dentro' e il 'fuori' delle narrazioni

    Directory of Open Access Journals (Sweden)

    Maria Ermelinda De Carlo

    2006-09-01

    Full Text Available Tra le righe di uno scritto, attraverso le rappresentazioni e le interpretazioni, è possibile ritrovare schegge di un originale smarrito, ma non si può ricostruire oggettivamente e interamente la vita veramente vissuta. La scelta sintagmatica e paradigmatica, consapevole e/o inconsapevole, nasce infatti da un’impalcatura, da schemi mentali con cui l’uomo convive da sempre. Una storia e una frase dicono molto di più di quel che dicono. La densità di significazione e tutti i mondi che ci sono dietro ad alcuni sostantivi, verbi, avverbi, aggettivi restano il più delle volte un segreto. Il punto di vista narrativo si pone, dunque, come potenziale chiave euristica ed ermeneutica in grado di esplorare e recuperare patrimoni di esperienze di vita dei soggetti. La scrittura consente al soggetto di raccontarsi e di raccontare un io nascosto e rappresenta un tentativo di strapparsi quella ‘maschera di ferro’ che nasconde le emozioni, di andare ‘oltre la soglia’, di dare sfogo ad un’identità più o meno autentica, di comprendere orientamenti e percorsi di senso. Essa è l’esito di chi narra che, uscito dalla polarità dello schema lineare della vita, affianca se stesso in modo tale da avere uno sguardo sul sistema di insieme di cui è parte.

  1. Il monastero di Bobbio in età altomedievale

    Directory of Open Access Journals (Sweden)

    Eleonora Destefanis

    2003-11-01

    Full Text Available Il monastero di Bobbio, sorto sull’Appennino piacentino per iniziativa di S. Colombano e con il sostegno del re longobardo Agilulfo, ha conosciuto una lunga storia di studi che ne hanno messo di volta in volta in luce l’importanza come centro scrittorio e di raccolta di testi, il ruolo di primo piano quale interlocutore delle monarchie avvicendatesi nel corso dell’altomedioevo, la posizione di spicco nell’esperienza del monachesimo insulare sul Continente, riflessa da una cospicua produzione ...

  2. QUESTIONI ATTRIBUTIVE NEL MEDIOEVO SPAGNOLO "IL LIBRO DE ALEXANDRE"

    OpenAIRE

    MERCURI, LOREDANA

    2011-01-01

    Oggetto di studio è stato il Libro de Alexandre, un poema spagnolo della prima metà del XIII secolo, di cui si è tentata un'attribuzione più certa utilizzando un nuovo sistema informatico. Gli studi critici finora effettuati, infatti, sono discordi sull’argomento, poiché i due manoscritti conservati dell’opera riportano nella strofa finale del poema il nome di Juan Lorenzo de Astorga (ms. O) e il nome di Gonzalo de Berceo (ms. P). Nell'elaborato dopo aver introdotto i tratti che caratterizzan...

  3. Changes of serum levels of some relevant cytokine (IL-2, IL-6, TNF-α) after antithyroid treatment in patients with graves' disease

    International Nuclear Information System (INIS)

    Ren Xiaohua; Jiang Boyong

    2010-01-01

    Objective: To study the effect of antithyroid treatment on the changes of serum levels of IL-2, IL-6 and TNF-α in patients with Graves' disease. Methods: Serum levels of IL-2, IL-6 and TNF-α were measured with RIA in 30 patients with Graves' disease (both before and after treatment with antithyroid drug) and 30 controls. Results: Before treatment serum levels of IL-6 and TNF-α in the patients were significantly higher than those in controls (P 0.05). Conclusion: Changes of serum IL-2, IL-6 and TNF-α levels might be important in the pathogenesis of Graves' disease. (authors)

  4. 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

  5. Association of of IL-1 receptor antagonist (IL-1RN) and interleukin-1β genes (IL-1β) polymorphisms with recurrent pregnancy loss in Iranian Azeri women.

    Science.gov (United States)

    Ali Rahmani, Seyyed; Paknejad, Zeynab; Mohammadkhanlou, Masoumeh; Daneshparvar, Marina

    2017-12-27

    Objective One of the most important problems in human reproduction is recurrent pregnancy loss (RPL). RPL is defined as three or more consecutive abortions in the first trimester of pregnancy. The association between the polymorphisms in the immunological factors and RPL was investigated. The aim of our study was to determine the association of interleukin receptor antagonist (IL-IRN) and interleukin-1β (IL-1β) polymorphisms with RPL in Iranian Azeri women. Materials and methods The study participants consisted of 100 women with RPL of Iranian Azeri origin. The control group comprised 100 age- and ethnically-matched healthy women of the same reproductive age. Genomic DNA was extracted from the whole blood and genotype determinations were performed using polymerase chain reaction (PCR) amplification followed by restriction fragment length polymorphism (RFLP) analysis. Results Our results showed no significant relationship between IL-1RN polymorphism and RPL. The homozygous state in -857 C/T variant was seen to be higher in RPL patients than in control subjects. Also frequency of wild type genotype was lower in RPL patients than in controls. However, this associations was not significant. Conclusion This study suggested that -511 C/T (rs16944) and -31 C/T (rs1143627) polymorphisms in IL-1β gene may not be involved in RPL in Iranian Azeri women. Also the promoter polymorphism of the IL-1RN gene may not play a role in the susceptibility to RPL.

  6. Gene variation in IL-7 receptor (IL-7R)α affects IL-7R response in CD4+ T cells in HIV-infected individuals

    DEFF Research Database (Denmark)

    Hartling, Hans Jakob; Ryder, Lars P.; Ullum, Henrik

    2017-01-01

    Optimal CD4+ T cell recovery after initiating combination antiretroviral treatment (cART) in HIV infection reduces risk of morbidity and mortality. T-allele homozygosity (‘TT’) in the single nucleotide polymorphism, rs6897932(C/T), in the IL-7 receptor α (IL-7RA) is associated with faster CD4+ T...... cell recovery after cART initiation compared to C-allele homozygosity in rs6897932 (‘CC’). However, underlying mechanisms are unknown. We aimed to examine potential mechanisms explaining the association between rs6897932 and CD4+ T cell recovery. Ten ‘TT’ and 10 ‘CC’ HIV-infected individuals matched...... on gender, age, and nadir and current CD4+ T cell counts were included in a cross-sectional study. ‘TT’ individuals had higher proportion of CD4+ T cells expressing pSTAT5 compared to ‘CC’ individuals after stimulating with IL-7, especially when co-stimulated with soluble IL7-RA (sIL-7RA). Furthermore, ‘TT...

  7. 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)

  8. A late IL-33 response after exposure to Schistosoma haematobium antigen is associated with an up-regulation of IL-13 in human eosinophils

    DEFF Research Database (Denmark)

    Wilson, S.; Jones, F. M.; Fofana, H. K. M.

    2013-01-01

    IL-33, a proposed alarmin, stimulates innate immune cells and Th2 cells to produce IL-13 and is rapidly upregulated upon antigen exposure in murine helminth infection. The human IL-33 response to helminth antigen was analysed in Malians infected with Schistosoma haematobium by disrupting parasite...... integrity via chemotherapy. Plasma IL-33 was measured pretreatment, and 24 h and 9 weeks post-treatment. At 24 h post-treatment, IL-33 levels were low. Nine week post-treatment IL-33 levels were elevated and were associated with an increase in intracellular IL-13 in eosinophils. Up......-regulation of intracellular IL-13 in eosinophils was also associated with eosinophil expression of ST2L, the IL-33 receptor. IL-33 may play an important downstream role in the human response to schistosome adult worm antigen exposure....

  9. 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.

  10. 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.

  11. Closely related glycosylation patterns of recombinant human IL-2 expressed in a CHO cell line and natural IL-2

    International Nuclear Information System (INIS)

    Vita, N.; Magazin, M.; Marchese, E.; Lupker, J.; Ferrara, P.

    1990-01-01

    We report here the study of the glycosylation pattern of human recombinant (r) IL2 expressed in a Chinese hamster ovary (CHO) cell line. The human rIL2 secreted by this high-producing recombinant CHO cell line was metabolically radiolabelled with [35S]-methionine, or with [3H]-glucosamine and [3H]-galactose, purified to homogeneity, and then characterized. The electrophoretic analysis of the [35S]-methionine-labelled proteins present in the culture medium of the CHO cell line showed that the rIL2 represents approximately 12% of the total secreted proteins. Furthermore, pulse-chase experiments showed that the glycosylated rIL2 is synthesized and secreted within 30 min. The point of attachment and the structure of the carbohydrate moiety of the rIL2 was determined by: amino-terminal sequencing and fingerprint analysis of the 3H-labelled rIL2, mass spectroscopy of the amino-terminal tryptic octapeptide, and carbohydrate analysis after enzymatic (Vibrio cholerae neuraminidase and Aspergillus oryzae beta-galactosidase) or sulfuric acid hydrolysis. The results indicate that the recombinant protein possesses a sugar moiety O-linked to the threonine residue at position 3 of the polypeptide chain, and that sialic acid, galactose and N-acetyl galactosamine are components of this carbohydrate moiety. Taken together these results suggest that the recombinant molecule is identical to natural IL2

  12. 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

  13. 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

  14. 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)

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

    Science.gov (United States)

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

    1999-04-01

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

  16. 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

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

    Science.gov (United States)

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

    2018-01-01

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

  18. 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

  19. 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

  20. Shear stress and interleukin-8 (IL-8) on the proliferation ...

    African Journals Online (AJOL)

    Endothelial progenitor cells (EPCs) derived from bone marrow, are also found ... into tissues and neovascularization, the cells are exposed to fluid shear stress. ... Both shear stress and IL-8 can influence the process of EPCs repair in wound.

  1. Deniss Karpak piirdus MM-il 26. kohaga

    Index Scriptorium Estoniae

    2008-01-01

    Vt. ka Linnaleht : Tallinn : na russkom jazõke, Linnaleht : Tartu 13. veebr., lk. 6. Austraalias Terrigalis purjetamise Laser-klassi MM-il lõpetas Deniss Karpak 26. kohal. Vt. ka Linnaleht : Tartu 14.veebr.

  2. Oriente within, Nord without: il meridionismo e i romantici inglesi

    Directory of Open Access Journals (Sweden)

    Luigi Cazzato

    2012-11-01

    Full Text Available Per Voltaire (1773 prima ed Hegel (2010 poi, la storia del progresso del mondo ha viaggiato seguendo il percorso geo-politico e climatico aristotelico 1: dal dispotico Oriente verso il libero Occidente; mentre per Montesquieu (1994 essa ha viaggiato anche dai paesi caldi del Sud, timorosi come i vecchi, verso i paesi freddi del Nord, coraggiosi come i giovani. L’Europa non si è vista solo come l’altro rispetto all’Oriente, ma anche come l’altro rispetto al suo Meridione: il presente moderno del Nord di contro al passato antico del Sud. Nella seconda metà del Settecento, il secolo della nascita dell’orientalismo come sapere organico all’impresa coloniale dell’Occidente, vennero gettati anche i semi della pianta del meridionismo, sapere organico all’impresa della costruzione della moderna identità europea. I romantici inglesi coltivarono questa pianta.

  3. Targeting IL-17 with ixekizumab in patients with psoriasis

    DEFF Research Database (Denmark)

    Dyring Andersen, Beatrice; Skov, Lone; Zachariae, Claus

    2015-01-01

    Psoriasis is a multifactorial chronic inflammatory skin disease of unknown etiology. Knowledge of the pathophysiology of psoriasis has evolved and identified IL-17 as a key pro-inflammatory mediator in psoriasis creating new medical avenues. Several agents targeting IL-17 or its receptor are in c......Psoriasis is a multifactorial chronic inflammatory skin disease of unknown etiology. Knowledge of the pathophysiology of psoriasis has evolved and identified IL-17 as a key pro-inflammatory mediator in psoriasis creating new medical avenues. Several agents targeting IL-17 or its receptor...... are in clinical trials for the treatment of moderate-to-severe psoriasis. This review focuses on the biological rationale and the results of clinical trials with ixekizumab, a humanized IgG4 monoclonal antibody. The currently available Phase I to III data indicate that ixekizumab is a well-tolerated promising...

  4. Particelle e interazioni fondamentali Il mondo delle particelle

    CERN Document Server

    Braibant, Sylvie; Spurio, Maurizio

    2009-01-01

    Il libro intende fornire le conoscenze teoriche e fenomenologiche di base della struttura della materia a livello subatomico, presentando in maniera coordinata concetti e caratteristiche della fisica nucleare e della fisica delle particelle elementari. Partendo da un livello di base (nomenclatura, classificazione, tecniche di accelerazione e di rivelazione delle particelle elementari), si passano in rassegna le proprietà delle interazioni fondamentali (elettromagnetica, debole e forte). Vengono descritti poi i risultati che confermano il Modello Standard del microcosmo, per terminare con i problemi ancora aperti. Per esempio, la violazione di CP attualmente misurata non spiega l’asimmetria materia-antimateria dell’Universo osservata; le oscillazioni dei neutrini e la quantità di materia oscura prevista dalla cosmologia sembrano richiedere qualcosa oltre il Modello Standard. Il libro è organizzato in modo da coprire gli argomenti dei corsi di Fisica Nucleare e Subnucleare della Laurea in Fisica, e dei c...

  5. Il XLIV Congresso della Società Italiana di Reumatologia

    Directory of Open Access Journals (Sweden)

    F. Oliviero

    2011-09-01

    Full Text Available Il 17-20 Ottobre 2007 al Lido di Venezia presso il Palazzo del Casinò e il Palazzo del Cinema si è svolto il XLIV Congresso Nazionale della Società Italiana di Reumatologia (SIR. Numerosi esperti nazionali e internazionali hanno esposto le più importanti acquisizioni nel campo della ricerca clinica e di base reumatologiche. I tre giorni del congresso sono stati caratterizzati da letture, sessioni scientifiche, corsi educazionali, incontri con gli esperti, sezioni poster, corsi di aggiornamento su temi speciali, e diversi simposi. Tra i temi affrontati, particolare rilievo è stato dedicato ai singoli fattori implicati nella patogenesi delle malattie reumatiche, quali le citochine, i fagociti, le cellule endoteliali, i linfociti, i fibroblasti e gli autoanticorpi. In questo ambito un contributo di rilievo è stato offerto dai numerosi relatori stranieri ospiti del convegno. Dal punto di vista clinico, sono...

  6. IL-10: A Multifunctional Cytokine in Viral Infections

    Directory of Open Access Journals (Sweden)

    José M. Rojas

    2017-01-01

    Full Text Available The anti-inflammatory master regulator IL-10 is critical to protect the host from tissue damage during acute phases of immune responses. This regulatory mechanism, central to T cell homeostasis, can be hijacked by viruses to evade immunity. IL-10 can be produced by virtually all immune cells, and it can also modulate the function of these cells. Understanding the effects of this multifunctional cytokine is therefore a complex task. In the present review we discuss the factors driving IL-10 production and the cellular sources of the cytokine during antiviral immune responses. We particularly focus on the IL-10 regulatory mechanisms that impact antiviral immune responses and how viruses can use this central regulatory pathway to evade immunity and establish chronic/latent infections.

  7. induced pulmonary fibrosis in mice via regulation of IL

    African Journals Online (AJOL)

    TRAF6, IL-33 and ST2 in lung tissue were determined by western blotting assay. Serum levels of ..... facilitate excessive tissue repair and fibrosis [20]. Therefore ... to cancer biology. ... liver regeneration, fibrosis and carcinogenesis. Hepatol.

  8. 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)

  9. Ilhaq al-Masa'il bi Nazairiha dan Penerapannya dalam Bahth al-Masa'il

    Directory of Open Access Journals (Sweden)

    Luthfi Hadi Aminuddin

    2013-11-01

    Full Text Available Abstract: Ilh}a>q al-Masa>’il bi Naz}a>iriha is one of the methods used by Nahdlatul Ulama in resisting the opinion based on (manhaji analytical concept of Islamic jurisprudence (the solution for complex social problems as the main purpose of Islamic shari’ah. As known that, up to now, ilh}a>q has been understood as a process of answering a new case by the way of equating to the old one which is written in the book called al-mu’tabarah. Such ilh}a>q has got many criticisms both from the definitions, procedures and its epistemogical footing. This paper is about to reveal how the NU clerics of Islam understand the concept of Ilh}a>q}, what its epistemological footing was and how the concept was applied in discussing many cases (bah}th al-masa>’il. Based on the writer’s study to several documents of decision results of NU that Ilh}a>q did not only simplify to equate the new cases with the old ones that have been freely discussed in the books of al-mu’tabarah, but both cases should have similar legal substance, that is, both should be under the decrees of laws of al-qawa> ‘id al-fiqhi>yah. Thus, Ilh}a>q is actually answering the problem by applying al-qawa>‘id al-fiqhi>yah, whereas the formulation al-qawa>‘id al-fiqhi>yah itself was set off from the examination of a number of furu>’ generated by qiya> s. This paper also found three variations of the implementation of Ilh}a>q in bah}th al-masa>’il. First, the application of Ilh}a>q was without mentioning al-qawa> ‘id al-fiqhi>yah which covered new cases (mulh}aq and the old case law that has been known in the books of fiqh (mulh}aq bih/attached to. Second, the application of Ilh}a>q was accompanied by mentioning mulh}aq bih and al-qawa> ‘id al-fiqhi>yah. Third, the application of Ilh}a>q, was only by the mentioning al-qawa> ‘id al-fiqhi>yah.

  10. Association between IL-1β polymorphisms and gastritis risk

    Science.gov (United States)

    Sun, Xiaoming; Cai, Hongxing; Li, Zhouru; Li, Shanshan; Yin, Wenjiang; Dong, Guokai; Kuai, Jinxia; He, Yihui; Jia, Jing

    2017-01-01

    Abstract Background: Helicobacter pylori (H. pylori) infection of the human stomach regularly leads to chronic gastric inflammation. The cytokine gene interleukin (IL)-1β has been implicated in influencing the pathology of inflammation induced by H. pylori infection. Currently, several studies have been carried out to investigate the association of IL-1β-511 (rs16944) and IL-1β-31 (rs1143627) polymorphisms with gastritis risk; however, the results are inconsistent and inconclusive. To assess the effect of IL-1β polymorphisms on gastritis susceptibility, we conducted a meta-analysis. Methods: Up to March 15, 2016, 2205 cases and 2289 controls were collected from 12 published case–control studies. Summarized odds ratios and corresponding 95% confidence intervals (CIs) for IL-1β-511 and IL-1β-31 polymorphisms and gastritis risk were estimated using fixed- or random-effects models when appropriate. Heterogeneity was assessed by chi-squared-based Q-statistic test, and the sources of heterogeneity were explored by subgroup analyses and logistic meta-regression analyses. Publication bias was evaluated by Begg funnel plot and Egger test. Sensitivity analyses were also performed. Results: The results provided evidences that the single nucleotide polymorphisms (SNPs) in IL-1β-31 might be associated with the gastritis risk, especially in the Caucasian population, while SNPs in the IL-1β-511 might not be. Conclusion: Our studies may be helpful in supplementing the disease monitoring of gastritis in the future, and additional studies to determine the exact molecular mechanisms might inspire interventions to protect the susceptible subgroups. PMID:28151895

  11. Hypnose : que se passe-t-il dans le cerveau ?

    OpenAIRE

    Touzet , Claude

    2017-01-01

    The Conversation; L'hypnose est un état de "transe" imposé au sujet qui permet d'obtenir de celui-ci qu'il se conforme aux suggestions qui lui sont faites indépendamment de leur véracité. Par exemple, le sujet n'éprouve pas de douleur alors même que nous savons que ce qu'il subit est douloureux.

  12. Transplant tolerance: a new role for IL-34

    OpenAIRE

    Kim, James I.; Turka, Laurence A.

    2015-01-01

    Immune-suppressive cell populations, including Tregs and suppressor monocytes, have been implicated in long-term survival of allografts in both human transplant recipients and animal models. The factors that drive differentiation and function of these cell populations are not completely understood. In this issue, Bézie and colleagues identify IL-34 as an important mediator of allograft tolerance in a rat model of heart transplantation. Their data support a model in which IL-34 production by T...

  13. Il Risorgimento in scena. Le donne in mostra”

    Directory of Open Access Journals (Sweden)

    Francesco Muollo

    2013-01-01

    Full Text Available Questo paper nasce in seguito alla raccolta dei lavori del convegno “IL RISORGIMENTO IN SCENA. LE DONNE IN MOSTRA”. Ciascuna delle tre giornate che hannoarticolato il convegno, sono dedicate al protagonismo femminile nel Risorgimento, rappresentate dal cinema, dalla danza e dall’ arte. Le arti figurative e sceniche hanno saputo, forse meglio dei libri, preservare la memoria delle donne che hanno fatto l’Italia.

  14. Le forze della natura il nuovo orizzonte della fisica

    CERN Document Server

    Davies, Paul C W

    1990-01-01

    Vero "cavallo di razza" della divulgazione scientifica, Paul Davies è uno dei rari fisici che sanno farsi seguire dal lettore comune anche quando affrontano argomenti difficili. Ne è una prova il presente volume, una delle migliori illustrazioni disponibili del microcosmo atomico e dell'incredibile fauna che lo abita : non solo la familiare triade protone-elettrone-neutrone, ma le ben più intriganti realtà che vanno sotto il nome di "colore", "incanto", stranezza".

  15. IL-17 inhibits chondrogenic differentiation of human mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Masahiro Kondo

    Full Text Available OBJECTIVE: Mesenchymal stem cells (MSCs can differentiate into cells of mesenchymal lineages, such as osteoblasts and chondrocytes. Here we investigated the effects of IL-17, a key cytokine in chronic inflammation, on chondrogenic differentiation of human MSCs. METHODS: Human bone marrow MSCs were pellet cultured in chondrogenic induction medium containing TGF-β3. Chondrogenic differentiation was detected by cartilage matrix accumulation and chondrogenic marker gene expression. RESULTS: Over-expression of cartilage matrix and chondrogenic marker genes was noted in chondrogenic cultures, but was inhibited by IL-17 in a dose-dependent manner. Expression and phosphorylation of SOX9, the master transcription factor for chondrogenesis, were induced within 2 days and phosphorylated SOX9 was stably maintained until day 21. IL-17 did not alter total SOX9 expression, but significantly suppressed SOX9 phosphorylation in a dose-dependent manner. At day 7, IL-17 also suppressed the activity of cAMP-dependent protein kinase A (PKA, which is known to phosphorylate SOX9. H89, a selective PKA inhibitor, also suppressed SOX9 phosphorylation, expression of chondrogenic markers and cartilage matrix, and also decreased chondrogenesis. CONCLUSIONS: IL-17 inhibited chondrogenesis of human MSCs through the suppression of PKA activity and SOX9 phosphorylation. These results suggest that chondrogenic differentiation of MSCs can be inhibited by a mechanism triggered by IL-17 under chronic inflammation.

  16. IL-1 inhibition in systemic juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Gabriella Giancane

    2016-12-01

    Full Text Available Systemic juvenile idiopathic arthritis (sJIA is the form of childhood arthritis whose treatment is most challenging. The demonstration of the prominent involvement of interleukin (IL-1 in disease pathogenesis has provided the rationale for the treatment with biologic medications that antagonize this cytokine. The three IL-1 blockers that have been tested so far (anakinra, canakinumab and rilonacept have all been proven effective and safe, although only canakinumab is currently approved for use in sJIA. The studies on IL-1 inhibition in sJIA published in the past few years suggest that children with fewer affected joints, higher neutrophil count, younger age at disease onset, shorter disease duration, or, possibly, higher ferritin level may respond better to anti-IL-1 treatment. In addition, it has been postulated that use of IL-1 blockade as first-line therapy may take advantage of a window of opportunity, in which disease pathophysiology can be altered to prevent the occurrence of chronic arthritis. In this review, we analyze the published literature on IL-1 inhibitors in sJIA and discuss the rationale underlying the use of these medications, the results of therapeutic studies, and the controversial issues.

  17. IL-10 Induction from Implants Delivering Pancreatic Islets and Hyaluronan

    Directory of Open Access Journals (Sweden)

    Paul L. Bollyky

    2013-01-01

    Full Text Available Local induction of pro-tolerogenic cytokines, such as IL-10, is an appealing strategy to help facilitate transplantation of islets and other tissues. Here, we describe a pair of implantable devices that capitalize on our recent finding that hyaluronan (HA promotes IL-10 production by activated T cells. The first device is an injectable hydrogel made of crosslinked HA and heparan sulfate loaded with anti-CD3/anti-CD28 antibodies and IL-2. T cells embedded within this hydrogel prior to polymerization go on to produce IL-10 in vivo. The second device is a bioengineered implant consisting of a polyvinyl alcohol sponge scaffold, supportive collagen hydrogel, and alginate spheres mediating sustained release of HA in fluid form. Pancreatic islets that expressed ovalbumin (OVA antigen were implanted within this device for 14 days into immunodeficient mice that received OVA-specific DO.11.10 T cells and a subsequent immunization with OVA peptide. Splenocytes harvested from these mice produced IL-10 upon re-challenge with OVA or anti-CD3 antibodies. Both of these devices represent model systems that will be used, in future studies, to further evaluate IL-10 induction by HA, with the objective of improving the survival and function of transplanted islets in the setting of autoimmune (type 1 diabetes.

  18. 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.

  19. 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.

  20. IL-33 induces IL-9 production in human CD4+ T cells and basophils

    DEFF Research Database (Denmark)

    Blom, Lars; Poulsen, Britta Cathrina; Jensen, Bettina M.

    2011-01-01

    blood. TGF-β has been described as a critical factor for IL-9 induction in Th2 cells; however, we found that TGF-β also induces co-production of IL-9 in purified, naïve (>99%) CD4(+)CD45RA(+)CD45RO(-)CD25(-) T cells differentiated towards a Th1 profile. Subsequently, it was demonstrated that TGF...

  1. Effect of Proinflammatory Cytokines (IL-6, TNF-α, and IL-1β on Clinical Manifestations in Indian SLE Patients

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    Vinod Umare

    2014-01-01

    Full Text Available Systemic lupus erythematosus (SLE is an inflammatory rheumatic disease characterized by production of autoantibodies and organ damage. Elevated levels of cytokines have been reported in SLE patients. In this study we have investigated the effect of proinflammatory cytokines (IL-6, TNF-α, and IL-1β on clinical manifestations in 145 Indian SLE patients. One hundred and forty-five healthy controls of the same ethnicity served as a control group. Clinical disease activity was scored according to SLEDAI score. Accordingly, 110 patients had active disease and 35 patients had inactive disease. Mean levels of IL-6, TNF-α, and IL-1β were found to be significantly higher in SLE patients than healthy controls (P<0.001. Mean level of IL-6 for patients with active disease (70.45±68.32 pg/mL was significantly higher (P=0.0430 than those of inactive disease patients (43.85±63.36 pg/mL. Mean level of TNF-α was 44.76±68.32 pg/mL for patients with active disease while it was 25.97±22.03 pg/mL for those with inactive disease and this difference was statistically significant (P=0.0161. Similar results were obtained for IL-1β (P=0.0002. Correlation between IL-6, TNF-α, and IL-1β serum levels and SLEDAI score was observed (r=0.20, r=0.27, and r=0.38, resp.. This study supports the role of these proinflammatory cytokines as inflammatory mediators in active stage of disease.

  2. IL-33-responsive innate lymphoid cells are an important source of IL-13 in chronic rhinosinusitis with nasal polyps.

    Science.gov (United States)

    Shaw, Joanne L; Fakhri, Samer; Citardi, Martin J; Porter, Paul C; Corry, David B; Kheradmand, Farrah; Liu, Yong-Jun; Luong, Amber

    2013-08-15

    Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP) are associated with Th1 and Th2 cytokine polarization, respectively; however, the pathophysiology of CRS remains unclear. The importance of innate lymphoid cells in Th2-mediated inflammatory disease has not been clearly defined. The objective of this study was to investigate the role of the epithelial cell-derived cytokine IL-33 and IL-33-responsive innate lymphoid cells in the pathophysiology of CRS. Relative gene expression was evaluated using quantitative real-time polymerase chain reaction. Innate lymphoid cells in inflamed ethmoid sinus mucosa from patients with CRSsNP and CRSwNP were characterized using flow cytometry. Cytokine production from lymphoid cells isolated from inflamed mucosa of patients with CRS was examined using ELISA and intracellular cytokine staining. Elevated expression of ST2, the ligand-binding chain of the IL-33 receptor, was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP and healthy control subjects. An increased percentage of innate lymphoid cells was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP. ST2(+) innate lymphoid cells are a consistent source of IL-13 in response to IL-33 stimulation. Significant induction of IL-33 was observed in epithelial cells derived from patients with CRSwNP compared with patients with CRSsNP in response to stimulation with Aspergillus fumigatus extract. These data suggest a role for sinonasal epithelial cell-derived IL-33 and an IL-33-responsive innate lymphoid cell population in the pathophysiology of CRSwNP demonstrating the functional importance of innate lymphoid cells in Th2-mediated inflammatory disease.

  3. Increased systemic and epidermal levels of IL-17A and IL-1β promotes progression of non-segmental vitiligo.

    Science.gov (United States)

    Bhardwaj, Supriya; Rani, Seema; Srivastava, Niharika; Kumar, Ravinder; Parsad, Davinder

    2017-03-01

    Non-segmental vitiligo (NSV) results from autoimmune destruction of melanocytes. The altered levels of various cytokines have been proposed in the pathogenesis of vitiligo. However, the exact immune mechanisms have not yet been fully elucidated. To investigate the role of epidermal and systemic cytokines in active and stable NSV patients. Serum levels of inflammatory cytokines were checked in 42 active and 30 stable NSV patients with 30 controls. The lesional, perilesional and normal skin sections were subjected to H&E staining. The mRNA expression of inflammatory cytokines and their respective receptors were assessed by quantitative PCR in lesional skin of both active and stable NSV skin. The MITF and IL-17A were immunolocalized in lesional, perilesional and normal skin tissue. Significant increase in the expression of inflammatory cytokines, IL-17A, IL-1β and TGF-β was observed in active patients, whereas no change was observed in stable patients. A marked reduction in epidermal thickness was observed in lesional skin sections. Significant increase in IL-17A and significant decrease in microphthalmia associated transcription factor (MITF) expression was observed in lesional and perilesional skin sections. Moreover, qPCR analysis showed significant alterations in the mRNA levels of IL-17A, IL-1β, IFN-γ, TGF-β and their respective receptors in active and stable vitiligo patient samples. Increased levels of IL-17A and IL-1β cytokines and decreased expression of MITF suggested a possible role of these cytokines in dysregulation of melanocytic activity in the lesional skin and hence might be responsible for the progression of active vitiligo. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Il diritto all’assistenza linguistica dell’imputato straniero nel procedimento penale. Indagine conoscitiva presso il tribunale di Trieste

    OpenAIRE

    Mometti, Francesca

    2014-01-01

    Interviste a magistrati in servizio presso il Tribunale di Trieste e a interpreti/traduttori attivi presso la stessa istituzione hanno consentito di far emergere in che misura e attraverso quali pratiche venga garantito il diritto all’assistenza linguistica in ambito penale. L’incrocio tra i dati derivanti dall’analisi di un campione di fascicoli di liquidazione e quelli relativi ad alcuni fascicoli dibattimentali ha rivelato come si concretizzi nella prassi quotidiana la garanzia del diritto...

  5. Clinical evaluation of determination the changes on serum IL-2, IL-4 and IFN-γ levels after treatment in pediatric patients with acute nephritis

    International Nuclear Information System (INIS)

    Zhou Hong; Hu Yan; Wei Guoyu; Liu Ya

    2011-01-01

    Objective: To explore the clinical evaluation of the changes of determination of serum IL-2, IL-4 and IFN-γ levels after treatment in pediatric patients with acute nephritis. Methods: Serum IL-2 (with RIA), IL-4, IFN-γ (with ELISA) levels were determined both before and after treatment in 32 pediatric patients with acute nephritis and 35 normal controls. Results: The serum IL-4, IFN-γ levels were significantly higher in the patients than those in controls before treatment (P 0.05). Serum IL-2 levels were negatively correlated with IL-4, IFN-γ levels (r=-0.5536, -0.6012, P<0.01). Conclusion: Interaction of the serum IL-2, IL-4 and IFN-γ also participated in the pathogenesis of acute nephritis in pediatric patients, monitoring the changes of their serum levels was helpful for the management of the diseases and provider important clinical value. (authors)

  6. Acute myotube protein synthesis regulation by IL-6-related cytokines.

    Science.gov (United States)

    Gao, Song; Durstine, J Larry; Koh, Ho-Jin; Carver, Wayne E; Frizzell, Norma; Carson, James A

    2017-11-01

    IL-6 and leukemia inhibitory factor (LIF), members of the IL-6 family of cytokines, play recognized paradoxical roles in skeletal muscle mass regulation, being associated with both growth and atrophy. Overload or muscle contractions can induce a transient increase in muscle IL-6 and LIF expression, which has a regulatory role in muscle hypertrophy. However, the cellular mechanisms involved in this regulation have not been completely identified. The induction of mammalian target of rapamycin complex 1 (mTORC1)-dependent myofiber protein synthesis is an established regulator of muscle hypertrophy, but the involvement of the IL-6 family of cytokines in this process is poorly understood. Therefore, we investigated the acute effects of IL-6 and LIF administration on mTORC1 signaling and protein synthesis in C2C12 myotubes. The role of glycoprotein 130 (gp130) receptor and downstream signaling pathways, including phosphoinositide 3-kinase (PI3K)-Akt-mTORC1 and signal transducer and activator of transcription 3 (STAT3)-suppressor of cytokine signaling 3 (SOCS3), was investigated by administration of specific siRNA or pharmaceutical inhibitors. Acute administration of IL-6 and LIF induced protein synthesis, which was accompanied by STAT3 activation, Akt-mTORC1 activation, and increased SOCS3 expression. This induction of protein synthesis was blocked by both gp130 siRNA knockdown and Akt inhibition. Interestingly, STAT3 inhibition or Akt downstream mTORC1 signaling inhibition did not fully block the IL-6 or LIF induction of protein synthesis. SOCS3 siRNA knockdown increased basal protein synthesis and extended the duration of the protein synthesis induction by IL-6 and LIF. These results demonstrate that either IL-6 or LIF can activate gp130-Akt signaling axis, which induces protein synthesis via mTORC1-independent mechanisms in cultured myotubes. However, IL-6- or LIF-induced SOCS3 negatively regulates the activation of myotube protein synthesis. Copyright © 2017 the

  7. The roles of ADAM33, ADAM28, IL-13 and IL-4 in the development of lung injuries in children with lethal non-pandemic acute infectious pneumonia.

    Science.gov (United States)

    Baurakiades, Emanuele; Costa, Victor Horácio; Raboni, Sonia Mara; de Almeida, Vivian Rafaela Telli; Larsen, Kelly Susana Kunze; Kohler, Juliana Nemetz; Gozzo, Priscilla do Carmo; Klassen, Giseli; Manica, Graciele C M; de Noronha, Lucia

    2014-12-01

    ADAM28, ADAM33, IL-13, IL-4 and other cytokines (IL-6 and IL-10) seem to play important roles in the persistence and maintenance of acute inflammatory processes that ultimately lead to lung remodeling and pulmonary fibrosis, which may be responsible for the high morbidity and mortality rates associated with non-pandemic acute viral pneumonias in childhood. The aim of this study was to evaluate the roles of ADAM33, ADAM28, IL4, IL6, IL10 and IL13 in the development of inflammation and alveolar fibrosis due to lethal acute respiratory infections of the lower airway in a pediatric population, especially in those with viral etiology. For this study, 193 cases were selected, and samples from the cases were processed for viral antigen detection by immunohistochemistry and then separated into two groups: virus-positive (n=68) and virus-negative (n=125). Immunohistochemistry was performed to assess the presence of metalloproteinases (ADAM33 and ADAM28) and inflammatory cytokines (IL-4, IL-13, IL-6, IL-10) in the alveolar septa. The virus-positive group showed stronger immunolabeling for ADAM33, ADAM28, IL-4 and IL-13 (pplay important roles in pulmonary inflammatory reactions elicited against etiological viral agents. In addition, these mediators may affect the process of lung remodeling and the development of pulmonary fibrosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. IL18 and IL18R1 polymorphisms, lung CT and fibrosis: a longitudinal study in coal miners

    Energy Technology Data Exchange (ETDEWEB)

    Nadif, R.; Mintz, M.; Marzec, J.; Jedlicka, A.; Kauffmann, F.; Kleeberger, S.R. [INSERM, U780, Villejuif (France)

    2006-12-15

    It has been suggested that interleukin (IL)-18 plays a role in the development of inflammatory and fibrosing lung diseases. Associations of polymorphisms in the genes coding for IL-18 (108 /G-656T, C-607A, G-137C, T113G, C127T) and its receptor (IL8R1/C-69T) with coal workers' pneumoconiosis (CWP) were studied in 200 miners who were examined in 1990, 1994 and 1999. Coal-dust exposure was assessed according to job history and ambient measures. The main health outcome was lung computed tomography (CT) score in 1990. Internal coherence was assessed by studying CT score in 1994, 4-yr change in CT score and CWP incidence and prevalence. CT score in 1990 was a good predictor of radiographic grade in 1999 and, therefore, an appropriate subclinical quantitative trait. The IL18 -137C allele was associated with lower CT score in 1990 and 1994 (11.24 versus 1.69 and 1.57 versus 2.46, respectively), slower progression of CT score between 1990 and 1994 and lower pneumoconiosis prevalence in 1999 relative to the G allele (0.33 versus 0.77 and 8.2 versus 19.6%, respectively). Smoking- or dust-adjustment, and stratification on IL18R1 genotype and adjustment for haplotype effects did not change the conclusions. In conclusion, the results of the present study suggest a role for IL18 in reducing the development of this fibrosing lung disease.

  9. IL-6-induced Bcl6 variant 2 supports IL-6-dependent myeloma cell proliferation and survival through STAT3

    International Nuclear Information System (INIS)

    Tsuyama, Naohiro; Danjoh, Inaho; Otsuyama, Ken-ichiro; Obata, Masanori; Tahara, Hidetoshi; Ohta, Tsutomu; Ishikawa, Hideaki

    2005-01-01

    IL-6 is a growth and survival factor for myeloma cells, although the mechanism by which it induces myeloma cell proliferation through gene expression is largely unknown. Microarray analysis showed that some B-cell lymphoma-associated oncogenes such as Bcl6, which is absent in normal plasma cells, were upregulated by IL-6 in IL-6-dependent myeloma cell lines. We found that Bcl6 variant 2 was upregulated by STAT3. ChIP assay and EMSA showed that STAT3 bound to the upstream region of variant 2 DNA. Expression of p53, a direct target gene of Bcl6, was downregulated in the IL-6-stimulated cells, and this process was impaired by an HDAC inhibitor. Bcl6 was knocked down by introducing small hairpin RNA, resulting in decreased proliferation and increased sensitivity to a DNA damaging agent. Thus, STAT3-inducible Bcl6 variant 2 appears to generate an important IL-6 signal that supports proliferation and survival of IL-6-dependent myeloma cells

  10. 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.

  11. 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.

  12. Impaired IL-13-mediated functions of macrophages in STAT6-deficient mice.

    Science.gov (United States)

    Takeda, K; Kamanaka, M; Tanaka, T; Kishimoto, T; Akira, S

    1996-10-15

    IL-13 shares many biologic responses with IL-4. In contrast to well-characterized IL-4 signaling pathways, which utilize STAT6 and 4PS/IRS2, IL-13 signaling pathways are poorly understood. Recent studies performed with STAT6-deficient mice have demonstrated that STAT6 plays an essential role in IL-4 signaling. In this study, the functions of peritoneal macrophages of STAT6-deficient mice in response to IL-13 were analyzed. In STAT6-deficient mice, neither morphologic changes nor augmentation of MHC class II expression in response to IL-13 was observed. In addition, IL-13 did not decrease the nitric oxide production by activated macrophages. Taken together, these results suggest that the macrophage functions in response to IL-13 were impaired in STAT6-deficient mice, indicating that IL-13 and IL-4 share the signaling pathway via STAT6.

  13. IL-10 polymorphism and cell-mediated immune response to Chlamydia trachomatis

    DEFF Research Database (Denmark)

    Öhman, H.; Tiitinen, A; Halttunen, M.

    2006-01-01

    background. To study a relationship between interleukin-10 (IL-10) promoter -1082 polymorphism and cell-mediated immune response during C trachomatis infection in vitro, lymphocyte proliferation and cytokine (IL-10, IFN-gamma, TNF-alpha, IL-2, IL-4 and IL-5) secretion were analysed in subjects with different...... IL-10 genotypes. Enhanced IL-10 secretion and reduced antigen-specific lymphocyte proliferative and IFN-gamma responses were found in subjects with IL-10 -1082 GG genotype when compared to those with -1082 AA genotype. CD14+ monocytes were main source of IL-10 indicating that these cells...... are important regulators of the antigen-specific cell-mediated responses during active C trachomatis infection. We conclude that impaired cell-mediated response to C trachomatis is associated with IL-10 genotype in subjects with high IL-10 producing capacity. A comparison of immune markers between subjects...

  14. [Linee guida italiane per il trattamento dell'alcolismo].

    Science.gov (United States)

    Ceccanti, Mauro; Iannitelli, Angela; Fiore, Marco

    2018-01-01

    RIASSUNTO. L'Europa è la regione con il più forte consumo di alcol al mondo, con la più elevata percentuale di malattie totali e morti premature alcol-correlate. In Italia, questo fenomeno coinvolge circa il 13% della popolazione oltre i 18 anni e oltre il 25% dei pazienti ospedalizzati. Sfortunatamente, solo il 5% di questi pazienti vengono riconosciuti come persone affette da disturbo da uso di alcol (DUA). Una scarsa conoscenza della malattia, la mancanza di accesso alle cure e le poche risorse messe a disposizione nella gestione del problema sono tra le principali cause di ritardo nella diagnosi, alla fine con conseguenze cliniche molto più importanti e costose da gestire. Alla luce di ciò, abbiamo deciso di dedicare questo numero speciale della Rivista di psichiatria a una serie di articoli riguardanti le linee guida italiane per il trattamento della dipendenza da alcol. Realizzate in collaborazione con numerosi esperti e importanti società scientifiche italiane come il Centro di Riferimento Alcologico della Regione Lazio (CRARL), la Società Italiana Tossicodipendenze (SITD), la Società italiana per il Trattamento dell'Alcolismo e le sue Complicanze (SITAC), la Società Italiana Psichiatria delle Dipendenze (SIPDip), la Società Italiana Patologie da Dipendenza (SIPaD) e l'Istituto di Biologia Cellulare e Neurobiologia (IBCN-CNR), queste linee guida forniscono agli operatori una serie di raccomandazioni basate su prove di efficacia volte ad aumentare la conoscenza e un uso appropriato dei farmaci per le persone affette da DUA. Con la possibilità di un continuo aggiornamento, l'obiettivo principale di queste linee guida sarà quello di garantire l'omogeneità dei trattamenti e un incremento qualitativo nell'assistenza dei pazienti affetti da DUA, così da ridurre le conseguenze psicosociali e sulla salute pubblica di questa importante malattia psichiatrica.

  15. Developmental changes in circulating IL-8/CXCL8 isoforms in neonates.

    Science.gov (United States)

    Maheshwari, Akhil; Voitenok, Nikolai N; Akalovich, Svetlana; Shaik, Sadiq S; Randolph, David A; Sims, Brian; Patel, Rakesh P; Killingsworth, Cheryl R; Fallon, Michael B; Ohls, Robin K

    2009-04-01

    Interleukin-8 (IL-8/CXCL8) is widely expressed in fetal tissues although inflammatory changes are not seen. Circulating IL-8 is comprised of an endothelial-derived [ala-IL-8](77) isoform and another, more potent [ser-IL-8](72) secreted by most other cells; [ala-IL-8](77) can be converted into [ser-IL-8](72) by proteolytic removal of an N-terminal pentapeptide from [ala-IL-8](77). In this study, we show [ala-IL-8](77) is the predominant circulating isoform of IL-8 in premature neonates but not in term neonates/adults, who have [ser-IL-8](72) as the major isoform. This isoform switch from the less potent [ala-IL-8](77) to [ser-IL-8](72) correlates with a maturational increase in the neutrophil chemotactic potency of plasma IL-8. The emergence of [ser-IL-8](72) as the major isoform is likely due to increased plasma [ala-IL-8](77)-convertase activity and/or changes in the cellular sources of IL-8. Developmental changes in IL-8 isoforms may serve to minimize its inflammatory effects in the fetus and also provide a mechanism to restore its full activity after birth.

  16. The emergence of the IL-36 cytokine family as novel targets for inflammatory diseases.

    Science.gov (United States)

    Walsh, Patrick T; Fallon, Padraic G

    2018-04-01

    The recently discovered interleukin (IL)-36 family of cytokines form part of the broader IL-1 family and are emerging as important mediators of inflammatory disease. The IL-36 subfamily consists of three ligands-IL-36α, IL-36β, and IL-36γ-and the natural antagonist IL-36Ra. The cytokines exert their effects through a specific IL-36 receptor consisting of IL-36R and IL-1RAcP chains. IL-36 cytokines can direct both innate and adaptive immune responses by acting on parenchymal, stromal, and specific immune cell subsets. In humans, inactivating mutations in the gene encoding the IL-36R antagonist, which lead to unregulated IL-36R signaling, lead to an autoinflammatory condition termed deficiency of the IL-36R antagonist, which primarily manifests as a severe form of pustular psoriasis. While such discoveries have prompted deeper mechanistic studies highlighting the important role of IL-36 cytokines in psoriatic skin inflammation, it is now evident that IL-36 cytokines can also play important roles in inflammatory disorders in other organs, such as the gastrointestinal tract and the lungs. Given these emerging roles, strategies to specifically target the expression and activity of the IL-36 family have the potential to uncover novel therapeutic approaches aimed at treating inflammatory diseases in humans. © 2016 New York Academy of Sciences.

  17. Rock bream (Oplegnathus fasciatus) IL-12p40: identification, expression, and effect on bacterial infection.

    Science.gov (United States)

    Zhang, Lu; Zhang, Bao-Cun; Hu, Yong-Hua

    2014-08-01

    IL-12p40, also called IL-12β, is a subunit of the proinflammatory cytokines interleukin (IL)-12 and IL-23. In teleost, IL-12p40 homologues have been identified in several species, however, the biological function of fish IL-12p40 is essentially unknown. In this work, we reported the identification and analysis of an IL-12p40, OfIL-12p40, from rock bream (Oplegnathus fasciatus). OfIL-12p40 is composed of 361 amino acids and possesses a conserved IL-12p40 domain and a WSxWS signature motif characteristic of known IL-12p40. Constitutive expression of OfIL-12p40 occurred in multiple tissues and was highest in kidney. Experimental infection with bacterial pathogen upregulated the expression of OfIL-12p40 in kidney and spleen in a time-dependent manner. Purified recombinant OfIL-12p40 (rOfIL-12p40) stimulated the respiratory burst activity of peripheral blood leukocytes in a dose-dependent manner. rOfIL-12p40 also enhanced the resistance of rock bream against bacterial infection and upregulated the expression of innate immune genes in kidney. Taken together, these results indicate that OfIL-12p40 possesses cytokine-like property and plays a role in immune defense against bacterial infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. High IL-17E and Low IL-17C Dermal Expression Identifies a Fibrosis-Specific Motif Common to Morphea and Systemic Sclerosis

    OpenAIRE

    Lonati, Paola Adele; Brembilla, Nicolò Costantino; Montanari, Elisa; Fontao, Lionel; Gabrielli, Armando; Vettori, Serena; Valentini, Gabriele; Laffitte, Emmanuel; Kaya, Gurkan; Meroni, Pier-Luigi; Chizzolini, Carlo

    2014-01-01

    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...

  19. IL10 single nucleotide polymorphisms are related to upregulation of constitutive IL-10 production and susceptibility to Helicobacter pylori infection.

    Science.gov (United States)

    Assis, Shirleide; Marques, Cintia Rodrigues; Silva, Thiago Magalhães; Costa, Ryan Santos; Alcantara-Neves, Neuza Maria; Barreto, Mauricio Lima; Barnes, Kathleen Carole; Figueiredo, Camila Alexandrina

    2014-06-01

    Helicobacter pylori infection is a strong risk factor for gastric cancer, likely due to the extensive inflammation in the stomach mucosa caused by these bacteria. Many studies have reported an association between IL10 polymorphisms, the risk of gastric cancer, and IL-10 production. The aim of the study was to evaluate the association between IL10 genetic variants, Helicobacter pylori infection, and IL-10 production by peripheral blood leukocytes in children. We genotyped a total of 12 single nucleotide polymorphisms in IL10 in 1259 children aged 4-11 years living in a poor urban area in Salvador, Brazil, using TaqMan probe based, 5' nuclease assay minor groove binder chemistry. Association tests were performed by logistic regression for Helicobacter pylori infection and linear regression for IL-10 spontaneous production (whole-blood cultures) including sex, age, and principal components for informative ancestry markers as covariates, using PLINK. Our results shown that IL10 single nucleotide polymorphisms rs1800896 (OR = 1.63; 95% CI = 1.11-2.39), rs3024491 (OR = 1.71; 95% CI = 1.14-2.57), rs1878672 (OR = 1.79; 95% CI = 1.19-2.68), and rs3024496 (OR = 1.48; 95% CI = 1.05-2.08) were positively associated with Helicobacter pylori infection. Eight single nucleotide polymorphisms were associated with spontaneous production of IL-10 in culture, of which three (rs1800896 and rs1878672, p = .04; rs3024491, p = .01) were strongly associated with infection by Helicobacter pylori. Our results indicate that IL10 variants rs1800896, rs3024491, rs1878672, and rs3024496 are more consistently associated with the presence of anti-H. pylori IgG by inducing increased production of IL-10. Further studies are underway to elucidate the role of additional genetic variants and to investigate their impact on the occurrence of gastric cancer. © 2014 John Wiley & Sons Ltd.

  20. Immunotherapy of human cancer with lak cells and IL-2

    International Nuclear Information System (INIS)

    Choi, Kyu Chul; Nam, Sang Yun; Ha, Youn Mun; Choi, Yong Mook

    1988-01-01

    The effects of adoptive immunotherapy with LAK cells and/or IL-2 were evaluated in 18 patients with advanced cancer for whom standard therapy had proved ineffective, from Jul. 1985 to Jan. 1988. Six patients were treated with LAK cells only, 4 patients treated with continuous IV infusion of IL-2 alone, and 8 patients treated with LAK cells plus IL-2. In a patient with hepatoma LAK cells and IL-2 were infused by selective catheterization to a branch of hepatic artery, in a patient with gastric cancer complicated by cancer peritonities LAK cells and IL-2 were infused to peritoneal cavity, and in a patient with renal cell carcinoma HLA-matched allogeneic LAK cells from 2 siblings were infused intravenously(8 times, total 2.49 X 10 10 cells). In the patient with gastric cancer who was treated by peritoneal infusion, LAK cells were induced from mononuclear cells obtained from ascites. Of 17 evaluable patients, 1(5.9%) had complete response(CR), 1(5.9%) had partial response (PR), 4(23.5%) had minimal responses(Min R), and 2(11.8%) had mixed responses(Mix R). Especially, of 7 evaluable patients treated with LAK cells plus IL-2, 1(14.3%) had CR, 1(14.3%) had PR, and 3(42.9%) had Min R. CR with relapse-free survival for 19 months was observed in a lung cancer (squamous cell carcinoma). PR was observed in a lung cancer, and Min R were observed in 2 hepatomas, 1 gastric cancer and 1 neuroblastoma. In 3 pediatric patients (3 to 7 years old) continuous infusion of IL-2 in dose-escalation mode were studied. They were able to tolerate 4,000,000 KH u/M 2 /day for 7 days of IL-2(1 KH u=1.1 BRMP u). Most of adult patients well tolerated 2,000,000 KH u/M 2 /day for 5 days of IL-2 in mode of continuous IV infusion. Most common side effects were chills and fever which could be prevented or minimized by premedication of antihistamine, indomethacin and acetaminophen, and IV infusion of demerol. Serious side effects were complicated by capillary leak syndrome which showed hypotension

  1. Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Dongmin [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom); Perros, Frédéric [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Caramori, Gaetano [Dipartimento di Scienze Mediche, Sezione di Medicina Interna e Cardiorespiratoria, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-Correlate, University of Ferrara, Ferrara (Italy); Meng, Chao [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom); Department of Geriatrics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China); Dormuller, Peter [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Chou, Pai-Chien [Airways Disease, National Heart and Lung Institute (United Kingdom); Church, Colin [Scottish Pulmonary Vascular Unit, University of Glasgow (United Kingdom); Papi, Alberto; Casolari, Paolo [Dipartimento di Scienze Mediche, Sezione di Medicina Interna e Cardiorespiratoria, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-Correlate, University of Ferrara, Ferrara (Italy); Welsh, David; Peacock, Andrew [Scottish Pulmonary Vascular Unit, University of Glasgow (United Kingdom); Humbert, Marc [Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France); Adcock, Ian M. [Airways Disease, National Heart and Lung Institute (United Kingdom); Wort, Stephen J., E-mail: s.wort@imperial.ac.uk [Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom)

    2014-08-15

    Highlights: • Nuclear IL-33 expression is reduced in vascular endothelial cells from PAH patients. • Knockdown of IL-33 leads to increased IL-6 and sST2 mRNA expression. • IL-33 binds homeobox motifs in target gene promoters and recruits repressor proteins. - Abstract: Idiopathic pulmonary arterial hypertension (IPAH) is an incurable condition leading to right ventricular failure and death and inflammation is postulated to be associated with vascular remodelling. Interleukin (IL)-33, a member of the “alarmin” family can either act on the membrane ST2 receptor or as a nuclear repressor, to regulate inflammation. We show, using immunohistochemistry, that IL-33 expression is nuclear in the vessels of healthy subjects whereas nuclear IL-33 is markedly diminished in the vessels of IPAH patients. This correlates with reduced IL-33 mRNA expression in their lung. In contrast, serum levels of IL-33 are unchanged in IPAH. However, the expression of the soluble form of ST2, sST2, is enhanced in the serum of IPAH patients. Knock-down of IL-33 in human endothelial cells (ECs) using siRNA is associated with selective modulation of inflammatory genes involved in vascular remodelling including IL-6. Additionally, IL-33 knock-down significantly increased sST2 release from ECs. Chromatin immunoprecipitation demonstrated that IL-33 bound multiple putative homeodomain protein binding motifs in the proximal and distal promoters of ST2 genes. IL-33 formed a complex with the histone methyltransferase SUV39H1, a transcriptional repressor. In conclusion, IL-33 regulates the expression of IL-6 and sST2, an endogenous IL-33 inhibitor, in primary human ECs and may play an important role in the pathogenesis of PAH through recruitment of transcriptional repressor proteins.

  2. 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.

  3. IL-6 RESPONSES TO GLYCAEMIC INDEX DURING RECOVERY FROM EXERCISE

    Directory of Open Access Journals (Sweden)

    S.H. Hasani

    2015-06-01

    Full Text Available Purpose: This study examined the effect of meal with different glycaemic index (GI on plasma IL-6 concentration and glucose metabolism after maximal lengthening contractions of the knee extensors. Using a cross-over design, Material : 10 healthy males completed 5 sets of 10 lengthening (eccentric contractions at 120% 1 repetition-maximum. Subjects were randomized to consume the GI beverage (high-GI, low-GI (15% weight per volume; 3 g/kg BM or placebo in three times within 10 min following exercise, and again at 50 and 110 min during recovery time. Blood samples were collected before exercise and after 0.60, 180 min and 24 h of recovery. Results: Concentration of plasma IL-6 in HGI group was less than LGI and Pla groups. IL-6 tended to significantly increase after exercise in recovery time in 3 groups (all P < 0.05, except for 24 hours (P = 1.00, furthermore there was significant difference for IL-6 between placebo and high glycemic groups in 3hours after exercise (P=.016. Concentration of serum CK in HGI group was less than LGI and Pla groups, CK was significantly elevated at all times points during recovery in 3 groups (all P < 0.05, except for 1 hour after exercise in HGI group (P = 0.31, but there was no significant difference for CK between groups. Conclusion: In summary, consuming HGI carbohydrate during recovery from exercise attenuate plasma IL-6 concentration.

  4. Radiosensitization of human endothelial cells by IL-24

    International Nuclear Information System (INIS)

    Meyn, R.E.

    2003-01-01

    Radiation therapy remains an important cancer treatment modality but despite improvements in dose delivery many patients still fail at their primary tumor site. Therefore, new strategies designed to improve local control are needed. Protocols combining radiation with anti-angiogenic agents might be of particular advantage based on their documented low toxicity. In this regard, we have been conducting preclinical investigations of a novel cytokine, mda7/IL-24. Our collaborators have shown that mda7/IL-24 protein targets the endothelial cells of the tumor microvascular system and has potent anti-angiogenic properties in both in vitro and in vivo assays. Recently, we have demonstrated that recombinant mda7/IL-24 protein radiosensitizes human endothelial cells in vitro. Specifically, 10 ng/ml of recombinant human IL-24 protein for 12 hrs reduced the survival at 2 Gy for human umbilical vein endothelial cells (HUVECs) from 0.33 to 0.12. We are also working on understanding the molecular basis for this radiosensitizing effect. Preliminary data suggest a model whereby mda7/IL-24 engages a specific receptor on the surface of endothelial cells and initiates a signal transduction pathway that modulates the cell's propensity for radiation-induced apoptosis and capacity for repairing radiation-induced DNA double strand breaks. Mechanistic insight gained from these studies may have implications for the actions of other anti-angiogenic agents and may generally explain the regulation of radiosensitivity imparted by growth factors and cytokines

  5. Il potere euristico dell’agapismo nella filosofia di Peirce

    Directory of Open Access Journals (Sweden)

    Ivo Assad Ibri

    2013-10-01

    Full Text Available La prima parte di questo saggio offre un’analisi del testo “La legge della mente”, in cui Peirce teorizza il potere di crescita e diffusione delle idee e formula la sua risposta alla classica domanda riguardo al modo in cui la mente possa influenzare la materia. A partire da un’analisi centrata sul duplice significato semantico della parola "affetto", il lavoro intende mostrare come la rottura da parte di Peirce con il dualismo cartesiano di mente e materia conduca a una sostanziale identità tra idealità e realtà per mezzo di una fusione metafisica di realismo e idealismo, in cui la materia viene considerata esclusivamente come un caso particolare della mente. La seconda parte mostra come le diverse forme di evoluzionismo discendano dalle tre categorie, ponendo in evidenza il concetto di agapismo, la dottrina dell’amore cosmico e creativo. Nella parte finale viene mostrato come il legame tra realismo e idealismo, così come le considerazioni di Peirce sull'evoluzionismo, costituiscano aspetti essenziali in vista di una giustificazione del successo storico della nostra capacità umana di elaborare congetture, ovvero di proporre ipotesi di successo per spiegare i fatti.

  6. 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.

  7. Informative management system for administrative management; Il sistema informativo per il reporting e il controllo di gestione di un ente complesso. Realizzazione di un prototipo

    Energy Technology Data Exchange (ETDEWEB)

    D' Onofrio, M.G.; Minelle, F. [Rome Univ. La Sapienza, Rome (Italy). Fac. di Scienze Matematiche, Fisiche e Naturali; Di Marco, R.A. [ENEA, Sede Centrale, Rome (Italy). Funzione Centrale Informatica

    1999-07-01

    The need to optimate the total functionality of the firm, introducing suitable Control System of inherit and merit evaluation concerning the administrative-management results, strengthens the assumption of responsibility from the managerial staff and promotes the operative and management decentralization. In this context assumes a remarkable importance the function of the Informative Management System which has got to assure, in a realistic, qualified and effectual way, a good support to all activities it can make easy, not only the standard working but also the achievement of the programmatic targets. In the present context, where the development of technology often exceeds that one of the organization structures, it is right to redesign the Informative Management System, considering that often the management informatics procedures are obsolete. The statement of the carried out work bases itself on the observation of the business management process: in order to achieve its targets, the firm transform some resources, each one with its own cycle of life, through stages of management classifiable in merit evaluation, decision, execution and control. These stages are carried out by treatment of the Information that represent the link among them, the main resource of the whole organization and the basis of the Informative Management System. Considering the information as an element characterizing the firm, in that it comes from a complicated system which permits to assert that the fulfilment of on effective and efficient management depends largely from its capacity to use the Information. [Italian] La necessita' di ottimizzare la funzionalita' complessiva dell'azienda, introducendo adeguati sistemi di controllo di merito e di valutazione dei risultati a livello amministrativo-gestionale rafforza l'assunzione di responsabilita' da parte della struttura dirigenziale e favorisce il decentramento gestionale e operativo. In questo contesto assume

  8. Informative management system for administrative management; Il sistema informativo per il reporting e il controllo di gestione di un ente complesso. Realizzazione di un prototipo

    Energy Technology Data Exchange (ETDEWEB)

    D' Onofrio, M G; Minelle, F [Rome Univ. La Sapienza, Rome (Italy). Fac. di Scienze Matematiche, Fisiche e Naturali; Di Marco, R A [ENEA, Sede Centrale, Rome (Italy). Funzione Centrale Informatica

    1999-07-01

    The need to optimate the total functionality of the firm, introducing suitable Control System of inherit and merit evaluation concerning the administrative-management results, strengthens the assumption of responsibility from the managerial staff and promotes the operative and management decentralization. In this context assumes a remarkable importance the function of the Informative Management System which has got to assure, in a realistic, qualified and effectual way, a good support to all activities it can make easy, not only the standard working but also the achievement of the programmatic targets. In the present context, where the development of technology often exceeds that one of the organization structures, it is right to redesign the Informative Management System, considering that often the management informatics procedures are obsolete. The statement of the carried out work bases itself on the observation of the business management process: in order to achieve its targets, the firm transform some resources, each one with its own cycle of life, through stages of management classifiable in merit evaluation, decision, execution and control. These stages are carried out by treatment of the Information that represent the link among them, the main resource of the whole organization and the basis of the Informative Management System. Considering the information as an element characterizing the firm, in that it comes from a complicated system which permits to assert that the fulfilment of on effective and efficient management depends largely from its capacity to use the Information. [Italian] La necessita' di ottimizzare la funzionalita' complessiva dell'azienda, introducendo adeguati sistemi di controllo di merito e di valutazione dei risultati a livello amministrativo-gestionale rafforza l'assunzione di responsabilita' da parte della struttura dirigenziale e favorisce il decentramento gestionale e operativo. In questo contesto assume notevole importanza la

  9. Variants in LTA, TNF, IL1B and IL10 genes associated with the clinical course of sepsis.

    Science.gov (United States)

    Montoya-Ruiz, Carolina; Jaimes, Fabián A; Rugeles, Maria T; López, Juan Álvaro; Bedoya, Gabriel; Velilla, Paula A

    2016-12-01

    The aim of this study was to explore the association between some SNPs of the TNF, LTA, IL1B and IL10 genes with cytokine concentrations and clinical course in Colombian septic patients. We conducted a cross-sectional study to genotype 415 septic patients and 205 patients without sepsis for the SNPs -308(G/A) rs1800629 of TNF; +252 (G/A) rs909253 of LTA; -511(A/G) rs16944 and +3953(C/T) rs1143634 of IL1B; and -1082(A/G) rs1800896, -819(C/T) rs1800871 and -592(C/A) rs1800872 of IL10. The association of theses SNPs with the following parameters was evaluated: (1) the presence of sepsis; (2) severity and clinical outcomes; (3) APACHE II and SOFA scores; and (4) procalcitonin, C-reactive protein, tumor necrosis factor, lymphotoxin alpha, interleukin 1 beta and interleukin 10 plasma concentrations. We found an association between the SNP LTA +252 with the development of sepsis [OR 1.29 (1.00-1.68)]; the SNP IL10 -1082 with sepsis severity [OR 0.53 (0.29-0.97)]; the TNF -308 with mortality [OR 0.33 (0.12-0.95)]; and the IL10 -592 and IL10 -1082 with admission to the intensive care unit (ICU) [OR 3.36 (1.57-7.18)] and [OR 0.18 (0.04-0.86)], respectively. None of the SNPs were associated with cytokine levels, procalcitonin and C-reactive protein serum concentrations, nor with APACHE II and SOFA scores. Our results suggest that these genetic variants play an important role in the development of sepsis and its clinical course.

  10. Il sistema EGNOS a supporto della navigazione sicura nei porti: il progetto SafePort

    Directory of Open Access Journals (Sweden)

    Antonio Casoria

    2012-09-01

    Full Text Available Il progetto SafePort, sviluppato all’interno del 7° Programma Quadro promosso dalla Unione Europea con la supervisione di European GNSS Agency (GSA che segue tutti i programmi applicativi inerenti ai sistemi GNSS europei, Galileo ed EGNOS, ha l’obbiettivo di migliorare la capacità recettiva dei porti europei, aumentando al contempo la sicurezza delle operazioni di navigazione, di attracco e di ormeggio. The EGNOS system to support safe navigation in ports: the project SafePORT SafePORT The project, developed within the 7 th Framework Programme  sponsored  by  European  Union  under  the  super-vision of European GNSS Agency (GSA, which follows all ap-plications relating to the European GNSS systems, Galileo and EGNOS, has the aim to improve receptive capacity of Europe-an ports, while increasing the safety of operations, navigation, docking and mooring.

  11. Il sistema EGNOS a supporto della navigazione sicura nei porti: il progetto SafePort

    Directory of Open Access Journals (Sweden)

    Antonio Casoria

    2012-09-01

    Full Text Available Il progetto SafePort, sviluppato all’interno del 7° Programma Quadro promosso dalla Unione Europea con la supervisione di European GNSS Agency (GSA che segue tutti i programmi applicativi inerenti ai sistemi GNSS europei, Galileo ed EGNOS, ha l’obbiettivo di migliorare la capacità recettiva dei porti europei, aumentando al contempo la sicurezza delle operazioni di navigazione, di attracco e di ormeggio.The EGNOS system to support safe navigation in ports: the project SafePORTSafePORT The project, developed within the 7 th Framework Programme  sponsored  by  European  Union  under  the  super-vision of European GNSS Agency (GSA, which follows all ap-plications relating to the European GNSS systems, Galileo and EGNOS, has the aim to improve receptive capacity of Europe-an ports, while increasing the safety of operations, navigation, docking and mooring.

  12. Comporre conoscenza: il collage come strategia meta-riflessiva

    Directory of Open Access Journals (Sweden)

    Elisabetta Biffi

    2015-09-01

    Full Text Available Il presente contributo intende riflettere sull’utilizzo di una tecnica artistica, il collage, all’interno della formazione degli insegnanti e degli educatori. Si tratta di una differente modalità di azione da parte dei formatori che è inserita nell’ambito dell’art-based research (McNiff, 2008, e dell’arts-informed research (Cole & Knowles, 2008. Per comprendere in modo approfondito questa scelta è necessario conoscere la nascita di questa tecnica e l’utilizzo che di questa hanno fatto vari artisti. Questo consente di delineare alcuni processi cognitivi riflessivi connessi alla pratica del collage che lo rendono strumento efficace in contesti formativi, soprattutto quando rivolti a insegnanti ed educatori. In chiusura, pertanto, si andranno presentando alcuni esempi di esperienze formative che hanno visto il ricorso al collage come strategia riflessiva.

  13. Inflammasome/IL-1β Responses to Streptococcal Pathogens

    Directory of Open Access Journals (Sweden)

    Christopher N. LaRock

    2015-10-01

    Full Text Available Inflammation mediated by the inflammasome and the cytokine IL-1β are some of the earliest and most important alarms to infection. These pathways are responsive to the virulence factors that pathogens use to subvert immune processes, and thus are typically activated only by microbes with potential to cause severe disease. Among the most serious human infections are those caused by the pathogenic streptococci, in part because these species numerous strategies for immune evasion. Since the virulence factor armament of each pathogen is unique, the role of IL-1β and the pathways leading to its activation varies for each infection. This review summarizes the role of IL-1β during infections caused by streptococcal pathogens, with emphasis on emergent mechanisms and concepts countering paradigms determined for other organisms.

  14. Consumo di suolo e degrado del territorio: il caso milanese

    Directory of Open Access Journals (Sweden)

    Francesco Vescovi

    2013-02-01

    Full Text Available La crescente scarsità di risorse pubbliche ha portato molti comuni italiani, complice una crescente cultura derogatoria nell’ambito della pianificazione, a diventare corresponsabili del degrado del paesaggio, alimentando artificiosamente il tasso di urbanizzazione del suolo. Mentre è evidente l’assoluta insostenibilità di un modello di “sviluppo” affidato ai meccanismi della speculazione immobiliare emerge chiaramente l’urgenza di una pianificazione strategica di scala intercomunale o metropolitana che sappia ottimizzare le sempre più scarse opportunità di rigenerazione di un territorio gravemente compromesso. I dati disponibili per il contesto milanese offrono la possibilità di indagare il fenomeno in maggior dettaglio.

  15. Il ‘volontariato’ dei richiedenti asilo in Italia

    Directory of Open Access Journals (Sweden)

    Martina Pasqualetto

    Full Text Available Riassunto L'articolo analizza la politica pubblica italiana che prevede il coinvolgimento dei richiedenti asilo in attività di 'volontariato' a favore delle amministrazioni locali per calmare il malcontento popolare causato dalla loro presunta inattività. In primo luogo l'autrice mette in discussione l'efficacia di tale policy e ne destruttura il discorso governativo mettendone in luce le mistificazioni. Mediante una ricerca esplorativa ispirata alla grounded theory si dimostra inoltre che la reale natura delle attività promosse risiede nel lavoro gratuito e che esse veicolano un messaggio di simbolica e percepita utilità dei profughi che impatta negativamente sull'immaginario collettivo rispetto al tema del diritto d'asilo.

  16. Tirocinio e videomentoring: il punto di vista degli studenti

    Directory of Open Access Journals (Sweden)

    Carla Maltinti

    2015-12-01

    Full Text Available Il presente contributo analizza i commenti espressi dagli studenti del Corso di Studi in Scienze della Formazione Primaria dell’Università di Firenze dopo aver partecipato al primo anno di un nuovo percorso di tirocinio integrato da videomentoring.I feedback forniti dai tirocinanti sono stati esaminati con un duplice scopo: (i acquisire i giudizi, le percezioni, le emozioni degli studenti in rapporto all’esperienza effettuata; (ii ricavarne indicazioni per migliorare la proposta formativa.I dati raccolti, analizzati attraverso una content analysis, toccano aspetti fondamentali della formazione iniziale degli insegnanti, quali il modellamento, l’importanza del rapporto con il tutor, la riflessività, l’imbarazzo dei tirocinanti nel vedersi in azione.

  17. Particelle e interazioni fondamentali Il mondo delle particelle

    CERN Document Server

    Braibant, Sylvie; Spurio, Maurizio

    2012-01-01

    Il libro intende fornire le conoscenze teoriche e fenomenologiche di base della struttura della materia a livello subatomico, presentando in maniera coordinata concetti e caratteristiche della fisica nucleare e della fisica delle particelle. Partendo da un livello di base (nomenclatura, classificazione, tecniche di accelerazione e di rivelazione delle particelle), si passano in rassegna le proprietà delle interazioni fondamentali (elettromagnetica, debole e forte). Vengono descritti poi i risultati che confermano il Modello Standard del microcosmo, per terminare con i problemi ancora aperti. Questa seconda edizione, riveduta, corretta e ampliata, nasce a seguito della traduzione in Inglese del libro effettuata dagli stessi autori. Oltre ad una rilettura critica e accurata di ogni paragrafo (necessaria quando si vuole esprimere in altra lingua un concetto), abbiamo inserito alcune figure nuove e una sezione che si riferisce ai primi risultati di fisica ottenuti con l'acceleratore LHC al CERN. Il numero di ese...

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

    International Nuclear Information System (INIS)

    Wang Guiying

    2008-01-01

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

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

    International Nuclear Information System (INIS)

    Wang Guanghui; Chen Chuanbing; Wang Xianwu

    2009-01-01

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

  20. 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)

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

    International Nuclear Information System (INIS)

    Feng Yue

    2011-01-01

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

  2. Clinical significance of determination of changes of serum IL-6, IL-10 and GM-CSF levels after treatment in pediatric patients with bronchial asthma

    International Nuclear Information System (INIS)

    Qin Wenjing

    2008-01-01

    Objective: To explore the changes of Serum IL-6, IL-10 and GM-CSF levels after treatment in pediatric patients with bronchial asthma. Methods: Serum IL-6, IL-10 and GM-CSF levels were measured with RIA in 33 pediatric patients with bronchial asthma both before and after treatment as well as in 30 controls. Results: Before treatment, the serum IL-6, IL-10 and GM-CSF levels were significantly higher than those in controls (P 0.05). Conclusion: Detection of serum IL-6, IL-10 and GM-CSF levels were useful for assessment of therapeutic efficacy and were of important clinical values in pediatric patients with bronchial asthma. (authors)

  3. Note of the methodological flaws in the paper entitled "Polymorphisms in IL-4/IL-13 pathway genes and glioma risk: an updated meta-analysis".

    Science.gov (United States)

    Wang, Ting-Ting; Li, Jin-Mei; Zhou, Dong

    2016-01-01

    With great interest, we read the paper "Polymorphisms in IL-4/IL-13 pathway genes and glioma risk: an updated meta-analysis" (by Chen PQ et al.) [1], which has reached important conclusions about the relationship between polymorphisms in interleukin (IL)-4/IL-13 pathway genes and glioma risk. Through quantitative analysis, the meta-analysis found no association between IL-4/IL-13 pathway genetic polymorphisms and glioma risk (Chen et al. in Tumor Biol 36:121-127, 2015). The meta-analysis is the most comprehensive study of polymorphisms in the IL-4/IL-13 pathway and glioma risk. Nevertheless, some deficiencies still exist in this meta-analysis that we would like to raise.

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

    International Nuclear Information System (INIS)

    Chen Xiaochao; Zhou Dongxia; Zhang Limin; Liu Hongshu

    2008-01-01

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

  5. Clinical significance of changes of serum IL-2, IL-6 and gastrin levels before and after treatment in patients with chronic eczema

    International Nuclear Information System (INIS)

    Mou Xudong; Ren Hong

    2009-01-01

    Objective: To explore the clinical significance of changes of serum IL-2, IL-6 and gastrin levels after treatment in patients with chronic eczema. Methods: Serum IL-2, IL-6 and gastin were detected with RIA both before and after treatment in 38 patients with chronic eczema and 35 controls. Results: Before treatment, serum IL-2 levels in the patients were significantly lower than those in the controls (P 0.05), however, the IL-2 levels were still significantly lower than those in controls (P>0.05). Conclusion: Serum IL-2, IL-6 and gastrin levels in the patients with chronic eczema were closely related to the severity of the diseases process and could be taken as indicator of treatment efficacy. (authors)

  6. An Epstein-Barr Virus MicroRNA Blocks Interleukin-1 (IL-1) Signaling by Targeting IL-1 Receptor 1.

    Science.gov (United States)

    Skinner, Camille M; Ivanov, Nikita S; Barr, Sarah A; Chen, Yan; Skalsky, Rebecca L

    2017-11-01

    Epstein-Barr virus (EBV) encodes >44 viral microRNAs (miRNAs) that are differentially expressed throughout infection, can be detected in Epstein-Barr virus (EBV)-positive tumors, and manipulate several biological processes, including cell proliferation, apoptosis, and immune responses. Here, we show that EBV BHRF1-2 miRNAs block NF-κB activation following treatment with proinflammatory cytokines, specifically interleukin-1β (IL-1β). Analysis of EBV PAR-CLIP miRNA targetome data sets combined with pathway analysis revealed multiple BHRF1-2 miRNA targets involved in interleukin signaling pathways. By further analyzing changes in cellular gene expression patterns, we identified the IL-1 receptor 1 (IL1R1) as a direct target of miR-BHRF1-2-5p. Targeting the IL1R1 3' untranslated region (UTR) by EBV miR-BHRF1-2-5p was confirmed using 3'-UTR luciferase reporter assays and Western blot assays. Manipulation of EBV BHRF1-2 miRNA activity in latently infected B cells altered steady-state cytokine levels and disrupted IL-1β responsiveness. These studies demonstrate functionally relevant BHRF1-2 miRNA interactions during EBV infection, which is an important step in understanding their roles in pathogenesis. IMPORTANCE IL-1 signaling plays an important role in inflammation and early activation of host innate immune responses following virus infection. Here, we demonstrate that a viral miRNA downregulates the IL-1 receptor 1 during EBV infection, which consequently alters the responsiveness of cells to IL-1 stimuli and changes the cytokine expression levels within infected cell populations. We postulate that this viral miRNA activity not only disrupts IL-1 autocrine and paracrine signaling loops that can alert effector cells to sites of infection but also provides a survival advantage by dampening excessive inflammation that may be detrimental to the infected cell. Copyright © 2017 American Society for Microbiology.

  7. ALLA SCOPERTA DEL PACKAGING DESIGN CON IL WEBQUEST

    Directory of Open Access Journals (Sweden)

    Antonietta Gobbis

    2013-01-01

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

  8. 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.

  9. IL1 receptor antagonist gene IL1-RN variable number of tandem repeats polymorphism and cancer risk: a literature review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Ying Zhang

    Full Text Available IL1 receptor antagonist (IL1RA and IL1beta (IL1β, members of the pro-inflammatory cytokine interleukin-1 (IL1 family, play a potential role against infection and in the pathogenesis of cancers. The variable number of tandem repeats (VNTR polymorphism in the second intron of the IL1 receptor antagonist gene (IL1-RN and a polymorphism in exon 5 of IL1B (IL1B+3954C>T, rs1143634 have been suggested in predisposition to cancer risk. However, studies have shown inconsistent results. To validate any association, a meta-analysis was performed with 14,854 cases and 19,337 controls from 71 published case-control studies for IL1-RN VNTR and 33 eligible studies contained 7,847 cases and 8917 controls for IL1B +3954. Odds ratios (ORs with 95% confidence intervals (CIs were calculated from comparisons to assess the strength of the association. There was significant association between the IL1-RN VNTR polymorphism and the risk of cancer for any overall comparison. Furthermore, cancer type stratification analysis revealed that there were significantly increased risks of gastric cancer, bladder cancer and other cancer groups. Infection status analysis indicated that the H. pylori or HBV/HCV infection and IL1-RN VNTR genotypes were independent factors for developing gastric or hepatocellular cancers. In addition, a borderline significant association was observed between IL1B+3954 polymorphism and the increased cancer risk. Although some modest bias could not be eliminated, this meta-analysis suggested that the IL1-RN VNTR polymorphisms may contribute to genetic susceptibility to gastric cancer. More studies are needed to further evaluate the role of the IL1B+3954 polymorphism in the etiology of cancer.

  10. IL-13 induces a bronchial epithelial phenotype that is profibrotic

    Directory of Open Access Journals (Sweden)

    Dinh Bao T

    2008-03-01

    Full Text Available Abstract Background Inflammatory cytokines (e.g. IL-13 and mechanical perturbations (e.g. scrape injury to the epithelium release profibrotic factors such as TGF-β2, which may, in turn, stimulate subepithelial fibrosis in asthma. We hypothesized that prolonged IL-13 exposure creates a plastic epithelial phenotype that is profibrotic through continuous secretion of soluble mediators at levels that stimulate subepithelial fibrosis. Methods Normal human bronchial epithelial cells (NHBE were treated with IL-13 (0, 0.1, 1, or 10 ng/ml for 14 days (day 7 to day 21 following seeding at an air-liquid interface during differentiation, and then withdrawn for 1 or 7 days. Pre-treated and untreated NHBE were co-cultured for 3 days with normal human lung fibroblasts (NHLF embedded in rat-tail collagen gels during days 22–25 or days 28–31. Results IL-13 induced increasing levels of MUC5AC protein, and TGF-β2, while decreasing β-Tubulin IV at day 22 and 28 in the NHBE. TGF-β2, soluble collagen in the media, salt soluble collagen in the matrix, and second harmonic generation (SHG signal from fibrillar collagen in the matrix were elevated in the IL-13 pre-treated NHBE co-cultures at day 25, but not at day 31. A TGF-β2 neutralizing antibody reversed the increase in collagen content and SHG signal. Conclusion Prolonged IL-13 exposure followed by withdrawal creates an epithelial phenotype, which continuously secretes TGF-β2 at levels that increase collagen secretion and alters the bulk optical properties of an underlying fibroblast-embedded collagen matrix. Extended withdrawal of IL-13 from the epithelium followed by co-culture does not stimulate fibrosis, indicating plasticity of the cultured airway epithelium and an ability to return to a baseline. Hence, IL-13 may contribute to subepithelial fibrosis in asthma by stimulating biologically significant TGF-β2 secretion from the airway epithelium.

  11. Il viaggio necessario: l'ottobre caldo della tragedia lampedusana

    Directory of Open Access Journals (Sweden)

    Samantha Viva

    2015-07-01

    Full Text Available Era ottobre. L’ottobre caldo e triste della tragedia lampedusana, del lutto e delle parole. L’ottobre dei 366 cadaveri dei migranti di origine eritrea e dei 150, tra uomini e donne, recuperati e salvati. Non era ancora scoppiato il caso al Centro di Primo Soccorso di Contrada Imbriacola, non era ancora stato chiuso per le docce della vergogna, per i trattamenti da lager con cui i dipendenti della Cooperativa che gestiva il Centro di Primo Soccorso, si prendevano cura dei migranti. Io ero andata lì a vedere cosa restava di quelle vite, e di quelli che continuavano ad arrivare, anche dopo.

  12. Il diritto di voto nell'ordinamento albanese e italiano

    OpenAIRE

    Vangjeli, Olsi

    2017-01-01

    L’Albania legifera in un Parlamento unicamerale composto da 140 deputati, eletti per un periodo di quattro anni. Il diritto di voto è ancora un argomento molto discusso in Albania Chiarire quello che è stato finora il viaggio e la dimensione del diritto di voto nella Repubblica dell’Albania, è un impegno importante, perché permette al popolo albanese e i suoi politici di guardare al futuro senza ripetere gli stessi errori del passato e di vedere al futuro e alla necessità di miglioramen...

  13. Il fondamento ultimo e l’ultimo fondamento

    OpenAIRE

    Belloni, Claudio

    2016-01-01

    L’ontologia di Franz Rosenzweig è costituita da tre elementi (Dio, mondo, uomo) irriducibili l’uno all’altro. Nelle intenzioni del filosofo, tale tripartizione del “nuovo pensiero” si contrappone all’intera t