Interleukin 17 inhibits progenitor cells in rheumatoid arthritis cartilage

Schminke, Boris; Trautmann, Sandra; Mai, Burkhard; Miosge, Nicolai; Blaschke, Sabine

doi:10.1002/eji.201545910

Cited by 25 publications

(21 citation statements)

References 25 publications

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“…Previous studies have reported that IL-17 plays an important role in various chronic diseases, including [17, 18] inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis [19]. Recently, evidence has indicated that IL-17 is related to many human cancers, including gastric cancer, breast cancer, and ovarian cancer [20-22].…”

Section: Introductionmentioning

confidence: 99%

IL-17 Activates the IL-6/STAT3 Signal Pathway in the Proliferation of Hepatitis B Virus-Related Hepatocellular Carcinoma

Luo

Wang

et al. 2017

Cell Physiol Biochem

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Background/Aims: We performed this study to determine the role of IL-17 in the immune microenvironment of hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC). Methods: HepG2 cells were treated with IL-17, STAT3 inhibitor S31-201 or IL-6 neutralizing monoclonal antibody (IL-6 mAb). Cell proliferation and migration were compared using the Cell Counting kit-8 (CCK-8) and Transwell assays, respectively. Real-time quantitative PCR (RT-qPCR), Western Blot, ELISA, immunofluorescence and histological staining were used for determining the expression levels of IL-17, IL-6, MCP-1, CCL5, VEGF, STAT3 and p-STAT3. HCC xenograft models were constructed in wild type and IL-17 knockout mice to clarify the effects of IL-17 on HCC in vivo. Results: Exogenous IL-17 enhanced the proliferation and migration of HepG2 cells, and it activated the phosphorylation of STAT3. RT-qPCR and ELISA showed that IL-17 promoted the expression of IL-6. The CCK-8 and Transwell assays showed that S31-201 or IL-6 mAb remarkably reversed the promotion effects of proliferation and migration by exogenous IL-17 in HepG2 cells. Additionally, IL-6 could promote the phosphorylation of STAT3, while IL-6 mAb acted as an inhibitor, and exogenous IL-17 could neutralize the inhibitory effects of IL-6 mAb. In vivo, compared to the wild type mice, the tumor volume, weight, density and size were decreased in IL-17 knockout mice. Additionally, the expression levels of p-STAT3, IL-6, MCP-1, CCL5 and VEGF decreased in IL-17 knockout mice. Conclusions: IL-17 can enhance the proliferation of HepG2 cells in vitro and in vivo via activating the IL-6/STAT3 pathway. Therefore, the IL-17/IL-6/STAT3 signaling pathway is a potential therapeutic target for HBV-related HCC.

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Section: Introductionmentioning

confidence: 99%

IL-17 Activates the IL-6/STAT3 Signal Pathway in the Proliferation of Hepatitis B Virus-Related Hepatocellular Carcinoma

Luo

Wang

et al. 2017

Cell Physiol Biochem

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“…This cytokine is produced by Th17 cells that are critical drivers of synovitis [66]. In the synovium, IL-17 stimulates the production of pro-inlammatory cytokines by rheumatoid synovial cells [67,68], triggers osteoclastogenesis [69] and impairs cartilage repair [70]. Methotrexate, a irst-line conventional therapeutic agent in RA, atenuates IL-17 production by peripheral blood mononuclear cells in vitro [71], supporting the pathogenic role of this cytokine.…”

Section: Role Of Il-17 Secretion By T Cellsmentioning

confidence: 99%

Physiology and Pathology of Autoimmune Diseases: Role of CD4+ T cells in Rheumatoid Arthritis

Castro-Sánchez¹,

Roda-Navarro²

2017

Physiology and Pathology of Immunology

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Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by synovial inlammation leading to bone erosion and to systemic manifestations in patients with long RA duration. Although the aetiology is unknown, several observations make currently clear that CD4 T cells play a key role in the pathogenesis: (1) RA associates with certain polymorphisms of HLA class II molecules, and (2) the repertoire and aging of CD4 T cells as well as the intracellular signalling mediating CD4 T cell activation are altered in RA patients. We describe herein the alterations found in CD4 T cells and the role of these cells in the development and progression of RA.

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“…Although a population of chondroprogenitor cells was identified in several studies of adult normal and diseased articular cartilage [54][55][56], significant repair of damaged articular cartilage in RA and OA by these cells is effete. This effect on cartilage repair may result from elevated levels of pro-inflammatory cytokines such as IL-17, which was recently shown to inhibit the chondrocyte maturation lineage emanating from progenitor cells in RA [57]. Therefore, even if chondrocyte precursor cells exist in adult articular cartilage which could potentially become authentic chondrocytes lost from articular cartilage via apoptosis or chondrocytes lost via diffusion of cartilage extracellular matrix fragments into synovial fluid, the reduction in chondrocyte vitality via apoptosis would be a challenging event to overcome, especially in a synovial joint microenvironment replete with pro-inflammatory cytokines.…”

Section: Introductionmentioning

confidence: 99%

Pharmacologic Interventions for Preventing Chondrocyte Apoptosis in Rheumatoid Arthritis and Osteoarthritis

Malemud¹

2018

Drug Discovery - Concepts to Market

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Chronic inflammation drives the progression of rheumatoid arthritis (RA) and osteoarthritis (OA) to synovial joint failure. The inflammatory state in both musculoskeletal diseases is associated with significantly elevated levels of pro-inflammatory cytokines in joint synovial fluid, which is best exemplified by increases in interleukin-1β (IL-1β), IL-6, IL-17, tumor necrosis factor-α, among others, as well as increased activity of soluble mediators such as nitric oxide and certain growth factors including vascular endothelial growth factor and fibroblast growth factor. The multitude of these factors activate chondrocyte signal transduction pathways resulting in programmed cell death, otherwise known as apoptosis as well as compromising chondrocyte autophagy. Importantly, chondrocyte apoptosis causes a loss of articular cartilage vitality which dampens cartilage repair mechanisms because at present, the possibility that chondrocyte progenitor cells could replace those differentiated chondrocytes lost via apoptosis remains debatable. Certain pharmacologic interventions which have been proven to induce apoptosis in various cancer cell studies in vitro suggest the possibility that drugs could be developed to specifically suppress or completely inhibit chondrocyte apoptosis in RA and OA cartilage. This review supports that contention and indicates that apoptosis can be inhibited by identifying novel cellular targets which promote apoptosis and autophagy.

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Interleukin 17 inhibits progenitor cells in rheumatoid arthritis cartilage

Cited by 25 publications

References 25 publications

IL-17 Activates the IL-6/STAT3 Signal Pathway in the Proliferation of Hepatitis B Virus-Related Hepatocellular Carcinoma

IL-17 Activates the IL-6/STAT3 Signal Pathway in the Proliferation of Hepatitis B Virus-Related Hepatocellular Carcinoma

Physiology and Pathology of Autoimmune Diseases: Role of CD4+ T cells in Rheumatoid Arthritis

Pharmacologic Interventions for Preventing Chondrocyte Apoptosis in Rheumatoid Arthritis and Osteoarthritis

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