BMP-2 and TGF-β1 inhibit the expression of the pro-inflammatory cytokine IL-34 in rheumatoid arthritis synovial fibroblasts

Marguerite Chemel 1, 2, 3, 4 Régis Brion 2, 3 Aude Segaliny 2, 3 Audrey Lamora 2, 3 Céline Charrier 2, 3 Bénédicte Brulin 2, 3 Yves Maugars 1, 4 Benoit Le Goff 1, 2, 3, 4 Dominique Heymann 5, 1, 2, 3, 4, * Franck Verrecchia 2, 3, *
* Auteur correspondant
1 CHU Nantes - Centre hospitalier universitaire de Nantes
2 Service de rhumatologie [Nantes]
3 Equipe LIGUE Nationale Contre le Cancer 2012
Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives
4 Department of Oncology and Metabolism [Sheffield, UK]
5 Sarcoma Research Unit - European Associated Laboratory [Sheffield, UK]
Abstract : Interleukin-34 (IL-34) is a pro-inflammatory cytokine implicated in rheumatoid arthritis (RA). The present study aimed to assess the IL-34 expression in response to two members of the TGF-β family, TGF-β1 and BMP-2, in synovial fibroblasts from RA patients. IL-34, TGF-β1 and BMP-2 productions were measured in patient synovial fluids by ELISA. IL-34 mRNA levels were quantified by qPCR in human synovial fibroblasts and murine mesenchymal stem cells (mMSCs). Pharmacological inhibitions were used to determine the involvement of ALK1 and ALK5 downstream TGF-β1 and BMP-2. IL-34, TGF-β1 and BMP-2 were expressed in synovial fluids from RA patients. We found a significant correlation between IL-34 and TGF-β1 expressions. Levels of both IL-34 and TGF-β1 were thus correlated with the total leukocyte counts in the synovial fluids. TGF-β1 and BMP-2 decreased IL-34 expression in the synovial fibroblasts or in mMSC in a dose- and time-dependent manner through respectively ALK5 and ALK1 pathways. In addition, TGF-β1 antagonized TNFα-induced IL-34 gene expression. This work identifies TGF-β1 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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American Journal of Pathology, American Society for Investigative Pathology, 2017, 187 (1), pp.156-162. 〈10.1016/j.ajpath.2016.09.015〉
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Marguerite Chemel, Régis Brion, Aude Segaliny, Audrey Lamora, Céline Charrier, et al.. BMP-2 and TGF-β1 inhibit the expression of the pro-inflammatory cytokine IL-34 in rheumatoid arthritis synovial fibroblasts. American Journal of Pathology, American Society for Investigative Pathology, 2017, 187 (1), pp.156-162. 〈10.1016/j.ajpath.2016.09.015〉. 〈inserm-01466118〉

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