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

Abstract

Galectin-9 (Gal9) has been postulated to have anti-infammatory properties based on the ability of exogenous Gal9 to induce apoptosis in synovial fbroblasts in animal models of rheumatoid arthritis (RA). Here we aimed to assess the potential role of endogenous Galectins, including Gal9, in the infammatory pathology of the RA synovium in humans. Firstly expression of Galectins 1–9 was determined in synovial fbroblasts (RASF) and dermal fbroblasts (DF) isolated from RA patients, the latter representing a non-infamed site. We then further challenged the cells with pro-infammatory TLR agonists and cytokines and assessed Galectin expression. Gal9 was found to be diferentially 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 efects 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 fbroblast viability suggesting that its role in RA is both pathogenic and pro-infammatory.

Publication DOI: https://doi.org/10.1038/s41598-018-31173-3
Divisions: Aston Medical School
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Related URLs: http://www.natu ... 598-018-31173-3 (Publisher URL)
PURE Output Type: Article
Published Date: 2018-08-27
Published Online Date: 2018-08-27
Accepted Date: 2018-07-30
Authors: Pearson, Mark J. ( 0000-0003-4553-4375)
Bik, Magdalena A.
Ospelt, Caroline
Naylor, Amy J.
Wehmeyer, Corinna
Jones, Simon W.
Buckley, Christopher D.
Gay, Steffen
Filer, Andrew
Lord, Janet M.

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