Endogenous Galectin-9 Suppresses Apoptosis in Human Rheumatoid Arthritis Synovial Fibroblasts.

Autor: Pearson MJ; Aston Medical School, Aston University, Birmingham, B4 7ET, UK.; MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, UK., Bik MA; NIHR Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, B15 2TT, UK., Ospelt C; Center of Experimental Rheumatology, Department of Rheumatology, University Hospital of Zurich, CH-8091, Zurich, Switzerland., Naylor AJ; NIHR Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, B15 2TT, UK.; MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, UK., Wehmeyer C; NIHR Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, B15 2TT, UK.; MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, UK., Jones SW; NIHR Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, B15 2TT, UK.; MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, UK., Buckley CD; NIHR Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, B15 2TT, UK.; MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, UK., Gay S; Center of Experimental Rheumatology, Department of Rheumatology, University Hospital of Zurich, CH-8091, Zurich, Switzerland., Filer A; NIHR Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, B15 2TT, UK.; MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, UK., Lord JM; NIHR Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, B15 2TT, UK. J.M.Lord@bham.ac.uk.; MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, UK. J.M.Lord@bham.ac.uk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2018 Aug 27; Vol. 8 (1), pp. 12887. Date of Electronic Publication: 2018 Aug 27.
DOI: 10.1038/s41598-018-31173-3
Abstrakt: Galectin-9 (Gal9) has been postulated to have anti-inflammatory properties based on the ability of exogenous Gal9 to induce apoptosis in synovial fibroblasts in animal models of rheumatoid arthritis (RA). Here we aimed to assess the potential role of endogenous Galectins, including Gal9, in the inflammatory pathology of the RA synovium in humans. Firstly expression of Galectins 1-9 was determined in synovial fibroblasts (RASF) and dermal fibroblasts (DF) isolated from RA patients, the latter representing a non-inflamed site. We then further challenged the cells with pro-inflammatory TLR agonists and cytokines and assessed Galectin expression. Gal9 was found to be differentially and abundantly expressed in RASF compared to DF. Agonists of TLR3 and TLR4, along with IFNgamma were also found to induce Gal9 expression in RASF. siRNA was then used to knock-down Gal9 expression in RASF and the effects of this on apoptosis and cell viability were assessed. Increased apoptosis was observed in RASF following Gal9 knock-down. We conclude that, unlike exogenous Gal9, endogenous Gal9 is protective against apoptosis and enhances synovial fibroblast viability suggesting that its role in RA is both pathogenic and pro-inflammatory.
Databáze: MEDLINE
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