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

Area of Science:

• Immunology
• Rheumatology
• Cell Biology

Background:

• Exogenous Galectin-9 (Gal9) has shown anti-inflammatory effects in animal models of rheumatoid arthritis (RA) by inducing apoptosis in synovial fibroblasts.
• The role of endogenous Gal9 in human RA synovium inflammation remains unclear.

Purpose of the Study:

• To investigate the expression and function of endogenous Galectins, specifically Gal9, in the inflamed synovium of RA patients.
• To determine if endogenous Gal9 influences the apoptosis and viability of rheumatoid arthritis synovial fibroblasts (RASF).

Main Methods:

• Quantified expression of Galectins 1-9 in RASF and dermal fibroblasts (DF) from RA patients.
• Stimulated cells with TLR agonists and cytokines (IFNgamma) to assess Galectin expression changes.
• Utilized siRNA to knock down Gal9 expression in RASF and evaluated effects on apoptosis and cell viability.

Main Results:

• Gal9 was expressed at higher levels in RASF compared to DF.
• TLR3, TLR4 agonists, and IFNgamma upregulated Gal9 expression in RASF.
• Knockdown of Gal9 in RASF led to increased apoptosis and reduced cell viability.

Conclusions:

• Endogenous Gal9 in RASF is protective against apoptosis, enhancing cell viability.
• This finding contrasts with the effects of exogenous Gal9, suggesting a pathogenic and pro-inflammatory role for endogenous Gal9 in RA.