The activin-follistatin anti-inflammatory cycle is deregulated in synovial fibroblasts.

Autor: Diller M; Department of Rheumatology and Clinical Immunology, Justus Liebig University Giessen, Campus Kerckhoff, Bad Nauheim, Benekestr: 2-8, 61231, Bad Nauheim, Germany., Frommer K; Department of Rheumatology and Clinical Immunology, Justus Liebig University Giessen, Campus Kerckhoff, Bad Nauheim, Benekestr: 2-8, 61231, Bad Nauheim, Germany., Dankbar B; Institute of Experimental Musculoskeletal Medicine, University Hospital Münster, Münster, Germany., Tarner I; Department of Rheumatology and Clinical Immunology, Justus Liebig University Giessen, Campus Kerckhoff, Bad Nauheim, Benekestr: 2-8, 61231, Bad Nauheim, Germany., Hülser ML; Department of Rheumatology and Clinical Immunology, Justus Liebig University Giessen, Campus Kerckhoff, Bad Nauheim, Benekestr: 2-8, 61231, Bad Nauheim, Germany., Tsiklauri L; Department of Rheumatology and Clinical Immunology, Justus Liebig University Giessen, Campus Kerckhoff, Bad Nauheim, Benekestr: 2-8, 61231, Bad Nauheim, Germany., Hasseli R; Department of Rheumatology and Clinical Immunology, Justus Liebig University Giessen, Campus Kerckhoff, Bad Nauheim, Benekestr: 2-8, 61231, Bad Nauheim, Germany., Sauerbier M; Department of Plastic, Hand and Reconstructive Surgery, BGU Frankfurt, Frankfurt, Germany., Pap T; Institute of Experimental Musculoskeletal Medicine, University Hospital Münster, Münster, Germany., Rehart S; Department of Orthopaedics and Trauma Surgery, Agaplesion Markus Hospital, Frankfurt, Germany., Müller-Ladner U; Department of Rheumatology and Clinical Immunology, Justus Liebig University Giessen, Campus Kerckhoff, Bad Nauheim, Benekestr: 2-8, 61231, Bad Nauheim, Germany., Neumann E; Department of Rheumatology and Clinical Immunology, Justus Liebig University Giessen, Campus Kerckhoff, Bad Nauheim, Benekestr: 2-8, 61231, Bad Nauheim, Germany. e.neumann@kerckhoff-klinik.de.
Jazyk: angličtina
Zdroj: Arthritis research & therapy [Arthritis Res Ther] 2019 Jun 10; Vol. 21 (1), pp. 144. Date of Electronic Publication: 2019 Jun 10.
DOI: 10.1186/s13075-019-1926-7
Abstrakt: Background: Activin A and follistatin exhibit immunomodulatory functions, thus affecting autoinflammatory processes as found in rheumatoid arthritis (RA). The impact of both proteins on the behavior of synovial fibroblasts (SF) in RA as well as in osteoarthritis (OA) is unknown.
Methods: Immunohistochemical analyses of synovial tissue for expression of activin A and follistatin were performed. The influence of RASF overexpressing activin A on cartilage invasion in a SCID mouse model was examined. RASF and OASF were stimulated with either IL-1β or TNFα in combination with or solely with activin A, activin AB, or follistatin. Protein secretion was measured by ELISA and mRNA expression by RT-PCR. Smad signaling was confirmed by western blot.
Results: In human RA synovial tissue, the number of activin A-positive cells as well as its extracellular presence was higher than in the OA synovium. Single cells within the tissue expressed follistatin in RA and OA synovial tissue. In the SCID mouse model, activin A overexpression reduced RASF invasion. In human RASF, activin A was induced by IL-1β and TNFα. Activin A slightly increased IL-6 release by unstimulated RASF, but decreased protein and mRNA levels of follistatin.
Conclusion: The observed decrease of cartilage invasion by RASF overexpressing activin A in the SCID mouse model appears to be mediated by an interaction between activin/follistatin and other local cells indirectly affecting RASF because activin A displayed certain pro-inflammatory effects on RASF. Activin A even inhibits production and release of follistatin in RASF and therefore prevents itself from being blocked by its inhibitory binding protein follistatin in the local inflammatory joint environment.
Databáze: MEDLINE
Externí odkaz: