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Interleukin‐29 induces receptor activator of NF‐κB ligand expression in fibroblast‐like synoviocytes via MAPK signaling pathways
Author(s) -
Xu Lingxiao,
Feng Xiaoke,
Shi Yumeng,
Wang Xiaoxi,
Kong Xiangqing,
Zhang Miaojia,
Liu Mei,
Tan Wenfeng,
Wang Fang
Publication year - 2015
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/1756-185x.12747
Subject(s) - rankl , mapk/erk pathway , proinflammatory cytokine , p38 mitogen activated protein kinases , signal transduction , activator (genetics) , kinase , cancer research , medicine , microbiology and biotechnology , receptor , inflammation , biology
Aim We previously reported that interleukin‐29 ( IL ‐29) was highly expressed in the blood and synovium of rheumatoid arthritis ( RA ) patients and contributed to synovial inflammation by induction of proinflammatory cytokine production. Given chronic inflammation can trigger the process of bone erosion, and receptor activator of nuclear factor‐κB ligand ( RANKL ) plays a crucial role in bone erosion of RA , we hypothesize that IL ‐29 mediates bone erosion in RA by regulation of RANKL expression. Here, we investigated the effect of IL ‐29 on RANKL expression in RA fibroblast‐like synoviocytes ( FLS ) and the relevant signaling pathways involved in it. Methods Primary fibroblast cells isolated from RA patients were stimulated by recombinant IL ‐29 in the presence or absence of anti‐ IL ‐29 antibody, and the expression levels of RANKL were assessed using real‐time polymerase chain reaction and immunostaining. Furthermore, the IL ‐29 signaling pathway for regulation of RANKL was also examined by Western blotting assay. Results IL ‐29 upregulated RANKL expression in a dose‐dependent manner, and blockade of IL ‐29 resulted in a significantly reduced RANKL expression in RA ‐ FLS . Incubation RA ‐ FLS with IL ‐29 (100 ng/mL) led to phosphorylation of ERK (extracellular signal‐regulated kinase), p38 and JNK (c‐Jun N‐terminal kinase). The expression of RANKL induced by IL ‐29 could be completely blocked by the inhibitors of mitogen‐activated protein kinase ( MAPK ) signal pathway, including PD 98059 ( ERK inhibitor), SB 203580 (p38 inhibitor) and SP 600125 ( JNK inhibitor). Conclusion These findings indicate, for the first time, that IL ‐29 could directly induce RANKL expression in RA ‐ FLS via MAPK signaling pathway, suggesting IL ‐29 might be a new target in the prevention of joint destruction in RA .