Interleukin 34 expression is associated with synovitis severity in rheumatoid arthritis patients.

ABSTRACT: OBJECTIVES: Interleukin (IL) 34 is a new cytokine implicated in macrophage differentiation and osteoclastogenesis. This study assessed IL-34 expression in the tissue of patients with rheumatoid arthritis (RA). METHODS: Immunohistochemistry was performed in synovial biopsies from patients with RA (n=20), osteoarthritis (n=3) or other inflammatory arthritis (n=4). IL-34 was detected in the synovial fluid by ELISA and its messenger RNA expression was studied by quantitative PCR in rheumatoid synovial fibroblasts after stimulation by tumour necrosis factor ? (TNF?) and IL-1?. Wild-type, jnk1(-/-)-jnk2(-/-) and nemo(-/-) murine fibroblasts and pharmacological inhibition were used to determine the involvement of nuclear factor kappa B (NF-?B) and JNK in that effect. RESULTS: IL-34 was expressed in 24/27 biopsies, with three samples from RA patients being negative. A significant association was found between IL-34 expression and synovitis severity. Levels of IL-34 and the total leucocyte count in synovial fluid were correlated. TNF? and IL-1? stimulated IL-34 expression by synovial fibroblasts in a dose/time-dependent manner through the NF-?B and JNK pathway. CONCLUSION: This work for the first time identifies IL-34 expression in the synovial tissue of patients with arthritis. This cytokine, as a downstream effector of TNF? and IL-1?, may contribute to inflammation and bone erosions in RA.

SUBMITTER: Chemel M 

PROVIDER: S-EPMC3413617 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature