Activin A suppresses interleukin-1-induced matrix metalloproteinase 3 secretion in human chondrosarcoma cells.
The objective was to investigate the effect of activin A on matrix metalloproteinase 3 (MMP-3) production and to identify the role of activin A in chondroprotection. SW1353 cells, a human chondrosarcoma cell line, were stimulated with interleukin (IL) 1alpha and tumor necrosis factor (TNF) alpha, and the concentrations of activin A, follistatin, and MMP-3 secreted into the culture media were measured by enzyme-linked immunosorbent assay (ELISA). Activin A was added to cell cultures in the presence of IL-1alpha or TNFalpha to determine its effect on the production of MMP-3 and sulfated glycosaminoglycan (sGAG) (measured by Alcian blue assay). To study the mechanism responsible for the chondroprotective effects of activin A, the production of IL-1 receptor antagonist (IL-1ra) and tissue inhibitor for metalloproteinases 1 (TIMP-1) was examined by ELISA. Addition of IL-1alpha did not affect the production of activin A by cultured SW1353 cells. IL-1alpha and activin A inhibited the production of follistatin. Stimulation of SW1353 cells with activin A suppressed IL-1alpha-induced, but not TNFalpha-induced, MMP-3 expression. Activin A had no effect on the production of sGAG, IL-1ra, or TIMP-1, although it suppressed the induction of TIMP-1 and IL-1ra by IL-1alpha. This novel finding of MMP-3 inhibition by activin A suggests a new role of activin A in cartilage remodeling. Activin A may have therapeutic potential for preventing cartilage degradation.
Chang
Deh-Ming
DM
Department of Rheumatology, Immunology and Allergy, Tri-Service General Hospital, National Defense Medical Center, #325 Cheng-Kung Road, Section 2, Neihu 114, Taipei, Taiwan. ming0503@ms3.hinet.net
Liu
Shao-Hsiang
SH
Lee
Herng-Sheng
HS
Lai
Jenn-Hung
JH
Chen
Chen-Hung
CH
D028341:Activins / Q000502:physiology*; D045744:Cell Line, Tumor; D019902:Chondrocytes / Q000378:metabolism*; D002813:Chondrosarcoma / Q000378:metabolism*; D038681:Follistatin / Q000378:metabolism; D006801:Humans; D053582:Interleukin-1alpha / Q000502:physiology*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*
D038681:Follistatin; D053582:Interleukin-1alpha; C422405:activin A; D028341:Activins; D019278:Matrix Metalloproteinase 3