title: IL-23 induces receptor activator of NF-kappaB ligand expression in fibroblast-like synoviocytes via STAT3 and NF-kappaB signal pathways.
abstract: 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-kappaB) 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-kappaB (parthenolide) or of the JAK II-STAT3 pathway (AG490), showing that the RANKL expression pathway is mediated by NF-kappaB 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.
authors.affiliation: Dalian University, Medical School Dalian, China. lixia416@yahoo.com.cn
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Kyoung-Woon
authors.initials: KW
authors.lastname: Kim
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.forename: Ji-Hyeon
authors.initials: JH
authors.lastname: Ju
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Kang
authors.forename: Hye-Joa
authors.initials: HJ
authors.lastname: Oh
authors.forename: Jun-Ki
authors.initials: JK
authors.lastname: Min
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Lee
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053759:Interleukin-23 / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010003:Osteoarthritis / Q000276:immunology*; D010010:Osteoclasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D053245:RANK Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D013583:Synovial Membrane / Q000473:pathology; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D053759:Interleukin-23; D016328:NF-kappa B; D053245:RANK Ligand; D050796:STAT3 Transcription Factor; D012717:Sesquiterpenes; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C002669:parthenolide