Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Knock-Down of Galectin-3 Inhibits Spontaneous and Lipopolysaccharide -Induced IL-6 Secretion In Fibroblast-Like Synoviocytes.
Arad, Uri, Angel-Korman, Avital, Amir, Sharon, Tzadok, Sharon, Seagal, Ortal, Elkayam, Ori, Caspi, Dan
Galectin-3 is a b-galactoside-binding lectin that plays an important role in the modulation of immune responses. Galectin-3 levels are increased in rheumatoid arthritis (RA) synovial tissue, synovial fluid and peripheral blood. Recombinant exogenous galectin-3 stimulates proinflammatory cytokine secretion by fibroblast-like synoviocytes (FLS). Our objective was to examine the effect of galectin-3 knock-down on spontaneous and lipopolysaccharide (LPS)-induced secretion of IL-6 in FLS from RA and osteoarthritis (OA) patients.
FLS from RA and OA patients were harvested from synovial fluid aspirates or directly from synovial tissue obtained during orthopedic surgery. The expression of galectin-3 was knocked-down by transfection of siRNAGal3 vs. siRNACtrl. The XTT test was used to evaluate cell viability, and galectin-3 knock-down was confirmed by western blotting. IL-6 secretion with and without lipopolysacharide (LPS)-stimulation was determined by ELISA.
Maximal knock-down of galectin-3 expression was observed on the 3rd day post transfection, in both RA and OA FLS (5075% knock-down). Galectin-3 knock-down caused a significant decrease in IL-6 secretion in both cell types (OA 46%, RA 21.5%, p<0.05). The inhibition of IL-6 secretion was not caused by decreased cell viability. LPS-stimulation caused a 35-fold increase in IL-6 secretion, and galectin-3 knock-down substantially inhibited LPS-induced IL-6 secretion (OA- 74%, RA- 33%, p<0.05).
siRNA-transfection is an effective means of suppressing galectin-3 expression in FLS. Knock-down of galectin-3 inhibited both spontaneous and LPS-induced IL-6 secretion. It appears that galectin-3 is an important component in the regulation of IL-6 secretion in FLS and may be targeted for suppressing joint inflammation.
To cite this abstract, please use the following information:
Arad, Uri, Angel-Korman, Avital, Amir, Sharon, Tzadok, Sharon, Seagal, Ortal, Elkayam, Ori, et al; Knock-Down of Galectin-3 Inhibits Spontaneous and Lipopolysaccharide -Induced IL-6 Secretion In Fibroblast-Like Synoviocytes. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1002