Interleukin 34 expression is associated with synovitis severity in rheumatoid arthritis patients
M Chemel, B Le Goff, R Brion, C Cozic… - Annals of the …, 2012 - ard.bmj.com
M Chemel, B Le Goff, R Brion, C Cozic, M Berreur, J Amiaud, G Bougras, S Touchais…
Annals of the rheumatic diseases, 2012•ard.bmj.comObjectives 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 …
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 …
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 α (TNFα) and IL-1β. Wild-type, jnk1−/−–jnk2−/− and nemo−/− murine fibroblasts and pharmacological inhibition were used to determine the involvement of nuclear factor kappa B (NF-κB) 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. TNFα and IL-1β stimulated IL-34 expression by synovial fibroblasts in a dose/time-dependent manner through the NF-κB 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 TNFα and IL-1β, may contribute to inflammation and bone erosions in RA.
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