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: College of Health & Life Sciences > Aston Medical School
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Publication ISSN: 2045-2322
Last Modified: 05 Feb 2024 08:30
Date Deposited: 03 Sep 2018 14:42
Full Text Link:
Related URLs: http://www.natu ... 598-018-31173-3 (Publisher URL)
PURE Output Type: Article
Published Date: 2018-08-27
Accepted Date: 2018-07-30
Authors: Pearson, Mark J. (ORCID Profile 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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