期刊
IMMUNOLOGY LETTERS
卷 127, 期 2, 页码 100-107出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.imlet.2009.10.012
关键词
Interleukin-23; Human fibroblast-like synoviocytes; RANKL; Autoimmune arthritis; STAT3/NF-kappa B
类别
资金
- Korea Science & Engineering Foundation through the RhRC (Rheumatism Research Center) at the Catholic University of Korea [R11-2002-098-05001-0]
- Korea Science and Engineering Foundation (KOSE F)
- Korean government [M10870060005-08N7006-00510]
Interleukin (IL)-23 stimulates T lymphocytes to produce inflammatory molecules, which can cause inflammatory arthritis. This study was undertaken to explore the role of IL-23 in stimulating the expression of the receptor activator of the nuclear factor kappa B (NF-kappa B) ligand (RANKL) and osteoclastogenic activity in human fibroblast-like synoviocytes (FLS). These cells were separated from the synovium of patients with rheumatoid arthritis (RA-FLS) and osteoarthritis (OA-FLS) and stimulated with IL-23. RANKL expression was measured by real-time polymerase chain reaction (PCR) amplification and immunostaining. Osteoclast precursor cells were cocultured with IL-23-stimulated RA-FLS and OA-FLS and subsequently stained for tartrate-resistant acid phosphatase (TRAP) activity. IL-23 upregulated RANKL expression in RA-FLS. The expression of RANKL mRNA and protein was blocked completely by inhibitors of NF-kappa B (parthenolide) or of the JAK II-STAT3 pathway (AG490), showing that the RANKL expression pathway is mediated by NF-kappa B and STAT3. TRAP-positive osteoclastogenesis was enhanced in IL-23-stimulated FLS. RA-FLS were more responsive to IL-23 in terms of their RANKL expression than OA-FLS or normal FLS. Thus, IL-23 appears to induce joint inflammation and bone destruction by stimulating RANKL expression in RA-FLS. These interactions between IL-23 and FLS indicate possible new therapeutic approaches for treating bone destruction in patients with inflammatory diseases. (C) 2009 Elsevier B.V. All rights reserved.
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