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

Background/Purpose:

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.

Methods:

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.

Results:

Maximal knock-down of galectin-3 expression was observed on the 3rd day post transfection, in both RA and OA FLS (50–75% 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).

Conclusion:

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
DOI:

Abstract Supplement

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