Search results for " Interleukin-6"
showing 10 items of 93 documents
Mast cells contribute to autoimmune diabetes by releasing interleukin-6 and failing to acquire a tolerogenic IL-10+ phenotype
2017
Mast cells (MCs) are innate immune cells that exert positive and negative immune modulatory functions capable to enhance or limit the intensity and/or duration of adaptive immune responses. Although MCs are crucial to regulate T cell immunity, their action in the pathogenesis of autoimmune diseases is still debated. Here we demonstrate that MCs play a crucial role in T1D pathogenesis so that their selective depletion in conditional MC knockout NOD mice protects them from the disease. MCs of diabetic NOD mice are overly inflammatory and secrete large amounts of IL-6 that favors differentiation of IL-17-secreting T cells at the site of autoimmunity. Moreover, while MCs of control mice acquire…
Involvement of interleukin-1 type 1 receptors in lipopolysaccharide-induced sickness responses
2017
Sickness responses to lipopolysaccharide (LPS) were examined in mice with deletion of the interleukin (IL)-1 type 1 receptor (IL-1R1). IL-1R1 knockout (1(0) mice displayed intact anorexia and HPA-axis activation to intraperitoneally injected LPS (anorexia: 10 or 120 mu g/kg; HPA-axis: 120 mu g/kg), but showed attenuated but not extinguished fever (120 g/kg). Brain PGE2 synthesis was attenuated, but Cox-2 induction remained intact. Neither the tumor necrosis factor-alpha (TNF alpha) inhibitor etanercept nor the IL -6 receptor antibody tocilizumab abolished the LPS induced fever in IL -1R1 KO mice. Deletion of IL -1R1 specifically in brain endothelial cells attenuated the LPS induced fever, b…
Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver
1998
Studies with tumor necrosis factor p55 receptor- and interleukin-6 (IL-6)-deficient mice have shown that IL-6 is required for hepatocyte proliferation and reconstitution of the liver mass after partial hepatectomy. The biological activities of IL-6 are potentiated when this cytokine binds soluble forms of its specific receptor subunit (sIL-6R) and the resulting complex interacts with the transmembrane signaling chain gp130. We show here that double transgenic mice expressing high levels of both human IL-6 and sIL-6R under the control of liver-specific promoters spontaneously develop nodules of hepatocellular hyperplasia around periportal spaces and present signs of sustained hepatocyte prol…
The transcription factor NFATc2 controls IL-6–dependent T cell activation in experimental colitis
2008
The nuclear factor of activated T cells (NFAT) family of transcription factors controls calcium signaling in T lymphocytes. In this study, we have identified a crucial regulatory role of the transcription factor NFATc2 in T cell–dependent experimental colitis. Similar to ulcerative colitis in humans, the expression of NFATc2 was up-regulated in oxazolone-induced chronic intestinal inflammation. Furthermore, NFATc2 deficiency suppressed colitis induced by oxazolone administration. This finding was associated with enhanced T cell apoptosis in the lamina propria and strikingly reduced production of IL-6, -13, and -17 by mucosal T lymphocytes. Further studies using knockout mice showed that IL-…
Stat3 and Gfi-1 Transcription Factors Control Th17 Cell Immunosuppressive Activity via the Regulation of Ectonucleotidase Expression
2012
International audience; Although Th17 cells are known to promote tissue inflammation and autoimmunity, their role during cancer progression remains elusive. Here, we showed that in vitro Th17 cells generated with the cytokines IL-6 and TGF-β expressed CD39 and CD73 ectonucleotidases, leading to adenosine release and the subsequent suppression of CD4(+) and CD8(+) T cell effector functions. The IL-6-mediated activation of the transcription factor Stat3 and the TGF-β-driven downregulation of Gfi-1 transcription factor were both essential for the expression of ectonucleotidases during Th17 cell differentiation. Stat3 supported whereas Gfi-1 repressed CD39 and CD73 expression by binding to thei…
Interferon-Beta Therapy of Multiple Sclerosis Patients Improves the Responsiveness of T Cells for Immune Suppression by Regulatory T Cells
2015
Multiple sclerosis (MS) is an inflammatory autoimmune disease characterized by imbalanced immune regulatory networks, and MS patient-derived T effector cells are inefficiently suppressed through regulatory T cells (Treg), a phenomenon known as Treg resistance. In the current study we investigated T cell function in MS patients before and after interferon-beta therapy. We compared cytokine profile, responsiveness for Treg-mediated suppression ex vivo and evaluated reactivity of T cells in vivo using a humanized mouse model. We found that CD4+ and CD8+ T cells of therapy-naive MS patients were resistant to Treg-mediated suppression. Treg resistance is associated with an augmented IL-6 product…
The transcription factor IFN regulatory factor–4 controls experimental colitis in mice via T cell–derived IL-6
2008
The proinflammatory cytokine IL-6 seems to have an important role in the intestinal inflammation that characterizes inflammatory bowel diseases (IBDs) such as Crohn disease and ulcerative colitis. However, little is known about the molecular mechanisms regulating IL-6 production in IBD. Here, we assessed the role of the transcriptional regulator IFN regulatory factor-4 (IRF4) in this process. Patients with either Crohn disease or ulcerative colitis exhibited increased IRF4 expression in lamina propria CD3+ T cells as compared with control patients. Consistent with IRF4 having a regulatory function in T cells, in a mouse model of IBD whereby colitis is induced in RAG-deficient mice by transp…
Interleukin-6 and its soluble receptor in patients with liver cirrhosis and hepatocellular carcinoma.
2006
AIM: To evaluate the immunohistochemical localization of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) on tumor tissue specimens from patients with hepatocellular carcinoma (HCC) and the serum levels of IL-6 and sIL-6R in a group of patients with HCC as well as liver cirrhosis (LC) in a group of patients with LC alone and in a control group. METHODS: Three groups of subjects were studied: group I (n = 83) suffering from HCC and LC, group II (n = 72) suffering from LC alone and group III (n = 42) as healthy controls. All patients had hepatitis C virus infection. Serum IL-6 and IL-6R levels were determined using a commercially available ELISA kit. Immunohistochemistry was performed using the…
Significance of serum Il-9 levels in inflammatory bowel disease
2015
IL-9, which may be an inflammatory or regulatory cytokine, can be experimentally produced in a Th17 or modified Th2 context in the presence of T cell receptor (TCR) stimulation. The primary aim of this study was to measure serum IL-9 levels in patients with inflammatory bowel disease (IBD), and evaluate their relationships with the patients’ clinical characteristics. The secondary aim was to determine the levels of interferon-γ (IFN (interferon)-γ), Th2 cytokines (IL-4, IL-5 and IL-13), and IL-6 in order to clarify the context of detectable peripheral cytokines in which IL-9 is produced. Venous blood samples of 43 IBD patients (20 with Crohn’s disease [CD] and 23 with ulcerative colitis [U…
MYD88 L265P mutation and interleukin‐10 detection in cerebrospinal fluid are highly specific discriminating markers in patients with primary central …
2021
Reliable biomarkers are needed to avoid diagnostic delay and its devastating effects in patients with primary central nervous system (CNS) lymphoma (PCNSL). We analysed the discriminating sensitivity and specificity of myeloid differentiation primary response (88) (MYD88) L265P mutation (mut-MYD88) and interleukin-10 (IL-10) in cerebrospinal fluid (CSF) of both patients with newly diagnosed (n = 36) and relapsed (n = 27) PCNSL and 162 controls (118 CNS disorders and 44 extra-CNS lymphomas). The concordance of MYD88 mutational status between tumour tissue and CSF sample and the source of ILs in PCNSL tissues were also investigated. Mut-MYD88 was assessed by TaqMan-based polymerase chain reac…