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

Scientific Reports
Mark J PearsonJanet M Lord

Abstract

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.

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Citations

Oct 11, 2019·PloS One·Kamila de Melo VilarMaira Galdino da Rocha Pitta
Aug 21, 2019·Stem Cell Research & Therapy·Fangqi LiRui Yang
Nov 17, 2019·Journal of Clinical Medicine·Tom J HarryvanSjoerd H van der Burg
Jul 1, 2020·Seminars in Immunopathology·Sandra M BloisGabriela Barrientos
Jan 26, 2021·Cellular Immunology·Preeti Moar, Ravi Tandon
Jun 23, 2020·Virus Research·Nara Gualberto CavalcantiMaira Galdino da Rocha Pitta
Apr 18, 2021·Cytokine & Growth Factor Reviews·Natalia PorębskaŁukasz Opaliński
May 11, 2021·Autoimmunity Reviews·Wang-Dong XuAn-Fang Huang
Aug 11, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Franziska KrautterAsif J Iqbal
Aug 10, 2021·Cellular Immunology·Wang-Dong XuXiao-Yan Liu
Aug 28, 2021·Biomedicines·Susanne N WijesingheSimon W Jones
Dec 19, 2021·Nature Communications·Cornelius H L KürtenRobert L Ferris

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Methods Mentioned

BETA
PCR
transfection
light
biopsies
biopsy

Software Mentioned

Graphpad Prism

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis