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Abstract
Background Interleukin-34 (IL-34) is a pro-osteoclastogenic cytokine, up-regulated by pro inflammatory cytokines, with a recently described role in rheumatoid arthritis (RA). TGF-b and BMP-2 are two members of the TGF-b family, whith an opposit role to the pro-inflammatory cytokines and that are also involved in rheumatoid synovitis.
Objectives The present study aimed to assess the IL-34 expression in response to two members of the TGF-b family, TGF-b1 and BMP-2, in synovial fibroblasts from RA patients.
Methods The IL-34, TGF-β1 and BMP-2 productions were measured in synovial fluids by ELISA. The IL-34 mRNA levels were quantified by qPCR in human synovial fibroblasts and murine mesenchymal stem cells (MSCs). Pharmacological inhibitions were used to determine the involvement of ALK1 and ALK5 downstream TGF-b1 and BMP-2.
Results IL-34, TGF-b1 and BMP-2 were expressed in synovial fluids from RA patients. We found a significant correlation between IL-34 and TGF-b1 expressions. Levels of both IL-34 and TGF-b1 were thus correlated with the total leukocyte counts in the synovial fluids. TGF-b1 and BMP-2 decreased Il-34 expression in the synovial fibroblasts or in mMSC in a dose/time dependent manner through respectively ALK5 and ALK1 pathways. In addition, TGF-b1 antagonized TNFa-induced IL-34 gene expression.
Conclusions This work identifies TGF-b1 and BMP-2 as potent inhibitors of IL-34 expression in RA synovial fibroblasts. These cytokines, as upstream inhibitors of IL-34, may thus contribute to antagonize inflammation and bone erosions in RA.
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Disclosure of Interest None declared