Search results for "Interleukin-18"
showing 10 items of 32 documents
Interleukin (IL)-22 receptor 1 is over-expressed in primary Sjogren's syndrome and Sjögren-associated non-Hodgkin lymphomas and is regulated by IL-18.
2015
Summary The aim of this study was to elucidate more clearly the role of interleukin (IL)-18 in modulating the IL-22 pathway in primary Sjögren's syndrome (pSS) patients and in pSS-associated lymphomas. Minor salivary glands (MSGs) from patients with pSS and non-specific chronic sialoadenitis (nSCS), parotid glands biopsies from non-Hodgkin lymphomas (NHL) developed in pSS patients, were evaluated for IL-18, IL-22, IL-22 receptor 1 (IL-22R1), IL-22 binding protein (IL-22BP) and signal transducer and activator of transcription-3 (STAT-3) expression. MSGs IL-22R1-expressing cells were characterized by confocal microscopy and flow cytometry in pSS, nSCS and healthy controls. The effect of recom…
Impact of inflammatory markers on cardiovascular mortality in patients with metabolic syndrome.
2008
Recent investigations suggest the inclusion of inflammatory markers in the definition of the metabolic syndrome (MS). The aim of this study was to address the role of C-reactive protein, fibrinogen, interleukin-6 (IL-6) and IL-18 (IL-18) on cardiovascular prognosis in accordance to MS.A total of 1263 patients with documented coronary artery disease were prospectively included. We defined MS (MS yes: N=533, 42.2%) as the presence of at least three of the following criteria: triglyceridesor=150 mg/dl; low high-density lipoprotein cholesterol (men:40 mg/dl women:50 mg/dl); body mass index greater than 30 kg/m; blood pressureor=130/85 mmHg; fasting glucoseor=100 mg/dl. In addition, we determine…
Targeting transcription factor Stat4 uncovers a role for interleukin-18 in the pathogenesis of severe lupus nephritis in mice
2011
Polymorphisms in the transcription factor Stat4 gene have been implicated as risk factors for systemic lupus erythematosus. Although some polymorphisms have a strong association with autoantibodies and nephritis, their impact on pathophysiology is still unknown. To explore this further we used signal transducers and activators of transcription 4 (Stat4) knockout MRL/MpJ-Fas(lpr)/Fas(lpr) (MRL-Fas(lpr)) mice and found that they did not differ in survival or renal function from Stat4-intact MRL-Fas(lpr) mice. Circulating interleukin (IL)-18 levels, however, were elevated in Stat4-deficient compared to Stat4-intact mice, suggesting that this interleukin might contribute to the progression of l…
Correlation of renal tubular epithelial cell-derived interleukin-18 up-regulation with disease activity in MRL-Faslpr mice with autoimmune lupus neph…
2002
Objective MRL-Faslpr mice spontaneously develop an autoimmune disease that mimics systemic lupus erythematosus in humans. Infiltrating T cells expressing interferon-γ (IFNγ) are responsible for the autoimmune kidney destruction in MRL-Faslpr mice, and interleukin-18 (IL-18) released by mononuclear phagocytes stimulates T cells to produce the IFNγ. Since MRL-Faslpr T cells are characterized by an overexpression of the IL-18 receptor accessory chain, we sought to determine the impact of IL-18 on the progression of lupus nephritis in MRL-Faslpr mice. Methods IL-18 expression in sera and kidney tissues from MRL-Faslpr mice was determined by enzyme-linked immunosorbent assay (ELISA), reverse tra…
Neutralization of interleukin-18 reduces severity in murine colitis and intestinal IFN-gamma and TNF-alpha production.
2001
Interleukin (IL)-18, initially described as interferon (IFN)-gamma-inducing factor, is expressed in the inflamed mucosa of patients with Crohn's disease. To investigate the role of IL-18 in intestinal inflammation, the effect of neutralizing antimurine IL-18 antiserum in dextran sulfate sodium (DSS)-induced colitis in BALB/c and C57BL/6 mice was examined. During a dose response of DSS, levels of colonic IL-18 increased parallel with clinical worsening. With the use of confocal laser microscopy, the increased IL-18 was localized to the intestinal epithelial layer. Anti-IL-18 treatment resulted in a dose-dependent reduction of the severity of colitis in both BALB/c and C57BL/6 mice. Colon sho…
Cellular Models and Assays to Study NLRP3 Inflammasome Biology
2020
The NLRP3 inflammasome is a multi-protein complex that initiates innate immunity responses when exposed to a wide range of stimuli, including pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). Inflammasome activation leads to the release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 and to pyroptotic cell death. Over-activation of NLRP3 inflammasome has been associated with several chronic inflammatory diseases. A deep knowledge of NLRP3 inflammasome biology is required to better exploit its potential as therapeutic target and for the development of new selective drugs. To this purpose, in the past few years, several tools have…
Differential haplotypic expression of the interleukin-18 gene
2007
Interleukin 18 (IL-18) is suspected to play an important role in atherosclerosis and plaque vulnerability. We had previously shown that haplotypes combining two IL18 gene polymorphisms in complete linkage disequilibrium, C-105T (rs360717) in 5'-untranslated region (UTR) and A+183G (rs5744292) in 3'-UTR, were related to IL-18 circulating levels and cardiovascular outcome, the C(-105) G(+183) haplotype being associated with lower IL-18 levels and lower cardiovascular risk. This study was aimed at investigating the functional role of the two polymorphisms and their haplotypes on IL18 expression levels. Allelic imbalance experiments conducted in 24 and 20 subjects heterozygous for the C-105T an…
IL-1β-converting enzyme (caspase-1) in intestinal inflammation
2001
IL-1β-converting enzyme (ICE; caspase-1) is the intracellular protease that cleaves the precursors of IL-1β and IL-18 into active cytokines. In the present study, the effect of ICE deficiency was evaluated during experimental colitis in mice. In acute dextran sulfate sodium-induced colitis, ICE-deficient (ICE KO) mice exhibited a greater than 50% decrease of the clinical scores weight loss, diarrhea, rectal bleeding, and colon length, whereas daily treatment with IL-1 receptor antagonist revealed a modest reduction in colitis severity. To further characterize the function of ICE and its role in intestinal inflammation, chronic colitis was induced over a 30-day time period. During this chron…
Dendritic cell activation by combined exposure to anti-CD40 plus interleukin (IL)-12 and IL-18 efficiently stimulates anti-tumor immunity
2008
Despite as yet limited clinical effectiveness, dendritic cell (DC)-based immunotherapy remains a promising approach for the treatment of cancer, but requires further improvement in its immunostimulatory effectiveness. Potent anti-tumor immunity often depends on the induction of type 1 (T(H)1) immune responses. Therefore, we combined different DC maturation stimuli that are known to induce T(H)1 immunity [anti-CD40, interleukin (IL)-12, IL-18], with the aim to trigger a T(H)1 driven anti-tumor CTL response. When compared with untreated DC or DC treated with anti-CD40 alone, DC matured with anti-CD40 plus IL-12 and IL-18 expressed significantly more IFN-gamma and IL-12, induced enhanced CD8(+…
Dynamics of gut mucosal and systemic Th1/Th2 cytokine responses in interferon-gamma and interleukin-12p40 knock out mice during primary and challenge…
2009
Cryptosporidium parvum is an intracellular parasite causing enteritis which can become life-threatening in the immunocompromised host. CD4+ T cells and interferon (IFN)-gamma play dominant roles in host immune response to infection. However, effector mechanisms that are responsible for recovery from infection are poorly understood. In the present study we analyzed mice deficient in IFN-gamma or interleukin (IL)-12 in parallel to C57BL/6 wild type mice as models for murine cryptosporidiosis. Our results identified IFN-gamma as the key cytokine in the innate as well as adaptive immunity during primary and also challenge C. parvum infection. Furthermore, both Th1 and Th2 cytokines appear to co…