JOURNAL ARTICLE

Interleukin-29 induces receptor activator of NF-κB ligand expression in fibroblast-like synoviocytes via MAPK signaling pathways

Lingxiao Xu, Xiaoke Feng, Yumeng Shi, Xiaoxi Wang, Xiangqing Kong, Miaojia Zhang, Mei Liu, Wenfeng Tan, Fang Wang
International Journal of Rheumatic Diseases 2015, 18 (8): 842-9
26420479

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 PD98059 (ERK inhibitor), SB203580 (p38 inhibitor) and SP600125 (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.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
26420479
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"