Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine                 (IL-4) concentrations in patients with systemic lupus erythematosus

Wong, Chun Kwok; Ho, C. Y.; Ek, Li; Lam, C. W. K.

doi:10.1191/096120300678828703

Cited by 448 publications

(351 citation statements)

References 37 publications

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“…[39] Administration of IL-12 to aging mice renders them vulnerable to the induction of experimental SLE induced by the monoclonal anti-DNA autoantibody bearing the 16/6Id. [40] In human patients with SLE, elevated levels of IL-12, IL-18 is observed [41][42][43], and the higher serum IL-12 levels are correlated with fever in subjects but not with renal diseases [44]. Moreover, PBMCs from patients with active SLE were found to be more sensitive to IL-12 by inducing phosphorylation of STAT3 and STAT4 [45].…”

Section: Il-12 Family Of Cytokines In Autoimmunitymentioning

confidence: 99%

Regulation of cytokine production during phagocytosis of apoptotic cells

2006

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Loss of self-tolerance and expansion of auto-reactive lymphocytes are the basis for autoimmunity. Apoptosis and the rapid clearance of apoptotic cells by phagocytes usually occur as coordinated processes that ensure regulated cellularity and stress response with non-pathological outcomes. Defects in clearance of apoptotic cells would contribute to the generation of self-reactive lymphocytes, which drive autoimmune disorders such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The IL-12 family of cytokines (IL-12, IL-23, and IL-27) and IL-10 are produced by phagocytic macrophages and play critical roles in the regulation of antigen-presenting cells (APCs) and effector lymphocytes during an immune response to pathogens. Inappropriate expression of these cytokines and their dysregulated activities have been strongly implicated in the pathogenesis of several autoimmune diseases. The production of pro-and anti-inflammatory cytokines by phagocytic APCs is delicately regulated during the ingestion of apoptotic cells as part of an intrinsic mechanism to prevent inflammatory autoimmune reactions. How apoptotic cell-derived signals regulate cytokine production is poorly understood. A recent study by our group demonstrated that phagocytosis of apoptotic cells by activated macrophages results in strong inhibition of IL-12 p35 gene expression by activating a novel transcription repressor, which we named GC-binding protein (GC-BP), through tyrosine dephosphorylation. We are also beginning to understand the molecular mechanisms underlying apoptotic cell-triggered production of IL-10 by phagocytes. These studies will help to elucidate some novel immune regulatory mechanisms and explore the regulation of immune responses to autoantigens with potentials to discover new therapeutic targets for the treatment of autoimmune disorders.

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Section: Il-12 Family Of Cytokines In Autoimmunitymentioning

confidence: 99%

Regulation of cytokine production during phagocytosis of apoptotic cells

2006

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“…This cytokine may play a role in T cell-triggered inflammation by stimulating stromal cells to secrete various cytokines and growth factors associated with inflammation (1)(2)(3)(4). A pathogenic role for IL-17 was found in organ allograft rejection (5), and increased IL-17 expression was detected in several diseases, such as systemic sclerosis (6), nephrotic syndrome (7), systemic lupus erythematosus (8), and rheumatoid arthritis (RA) (9,10). In contrast with the restricted expression of IL-17, the IL-17 receptor is ubiquitously expressed in virtually all cells and tissues.…”

mentioning

confidence: 99%

Treatment with a neutralizing anti‐murine interleukin‐17 antibody after the onset of collagen‐induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion

Lubberts¹,

Koenders²,

Oppers‐Walgreen³

et al. 2004

Arthritis & Rheumatism

659

457

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Objective. Interleukin-17 (IL-17) is a proinflammatory cytokine that is expressed in the synovium of rheumatoid arthritis (RA) patients. This T cell cytokine is implicated in the initiation phase of arthritis. However, the role of IL-17 during the effector phase of arthritis has still not been identified; this was the objective of the present study.Methods. Mice with collagen-induced arthritis (CIA) were treated with polyclonal rabbit anti-murine IL-17 (anti-IL-17) antibody-positive serum or normal rabbit serum after the first signs of arthritis. In addition, during a later stage of CIA mice were selected and treated with anti-IL-17 antibody or control serum. Arthritis was monitored visually, and joint pathology was examined radiologically and histologically. Systemic IL-6 levels were measured by enzyme-linked immunosorbent assay, and local synovial IL-1 and receptor activator of NF-B ligand (RANKL) expression was analyzed using specific immunohistochemistry.Results

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“…1 Moreover, IL-17 has been associated with various human diseases such as systemic lupus erythematosus, asthma, rheumatoid arthritis, and allograft rejection. [3][4][5][6] Recently, T H -17 cells derived by IL-23 were identified as a novel subset of CD4 þ effector T cells that produce IL-17A and IL-17F. 7 In addition, various cellular sources of IL-17 including CD4 þ memory T cells, CD8 þ memory T cells, neutrophils, and eosinophils have been identified.…”

mentioning

confidence: 99%

IL-17 stimulates the proliferation and differentiation of human mesenchymal stem cells: implications for bone remodeling

et al. 2009

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Interleukin-17 (IL-17) is a cytokine secreted primarily by T H -17 cells. Although IL-17 is primarily associated with the induction of tissue inflammation, the other biological roles of IL-17, including non-immune functions, have yet to be thoroughly explored. Here, we report that T-cell-produced IL-17 can induce proliferation of human bone marrow-derived mesenchymal stem cells (hMSCs) in a manner dependent on the generation of reactive oxygen species (ROS). Rac1 GTPase and NADPH oxidase 1 (Nox1) are activated by IL-17 to produce ROS, which in turn stimulates hMSC proliferation. The activation of the MEK-ERK pathway is also crucial for IL-17-dependent hMSC proliferation. TRAF6 and Act1 are required to activate Nox 1 and to phosphorylate MEK on IL-17 stimulation. Interestingly, IL-17 not only accelerates the proliferation of hMSCs, but also induces their migration, motility, and osteoblastic differentiation. Furthermore, IL-17 induces the expression of M-CSF and receptor activator of NF-jB ligand (RANKL) on hMSCs, thereby supporting osteoclastogenesis both in vivo and in vitro. On the basis of these results, we suggest that IL-17 can function as a signal to induce extensive bone turnover by regulating hMSC recruitment, proliferation, motility, and differentiation.

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Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus

Cited by 448 publications

References 37 publications

Regulation of cytokine production during phagocytosis of apoptotic cells

Regulation of cytokine production during phagocytosis of apoptotic cells

Treatment with a neutralizing anti‐murine interleukin‐17 antibody after the onset of collagen‐induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion

IL-17 stimulates the proliferation and differentiation of human mesenchymal stem cells: implications for bone remodeling

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