Differential induction of stromelysin mRNA by bovine articular chondrocytes treated with interferon-gamma and interleukin-1 alpha.
Articular chondrocytes from rheumatoid joints have been shown to express class II major histocompatibility (MHC) antigens that were correlated with the presence of interferon-gamma (IFN-gamma) in the inflamed joint. Chondrocytes expressing MHC antigens function as antigen presenting cells and thus stimulate lymphocyte proliferation. These responses suggest a powerful role for the IFN-gamma stimulation of chondrocytes. The present studies were designed to examine the functional role of chondrocytes exposed to IFN-gamma during cartilage degradation that occurs in synovial disease. Destruction of cartilage in arthritis is partially attributable to metalloproteinases released by the chondrocytes in response to interleukin-1 (IL-1). Bovine articular chondrocytes treated with interleukin-1 alpha (IL-1 alpha) produced enhanced levels of stromelysin mRNA, however, Northern blots could not determine the percentage of cells responding. Exposure of bovine articular chondrocytes to IFN-gamma induced the expression of bovine HLA-DR (boHLA-DR) antigen in 50% of the cells. Using a modified cell sorting technique, chondrocytes that expressed class II MHC antigens produced two fold greater stromelysin mRNA than chondrocytes that did not express this antigen. In contrast, collagen type II mRNA levels were similar in chondrocytes, regardless of the expression of class II MHC antigens. In situ hybridization studies showed that less than half of all cartilage chondrocytes were induced to synthesize stromelysin mRNA. These observations suggest that IFN-gamma stimulates specific subpopulations of chondrocytes to be functionally active in inflammation-induced metalloprotease secretion.
Quintavalla
J C
JC
Ciba-Geigy Pharmaceuticals, Summit, New Jersey 07901.
Berg
R A
RA
Beavis
A J
AJ
Piccoli
S P
SP
Rediske
J J
JJ
Kurkinen
M
M
Patrick
R A
RA
Robertson
F M
FM
D000818:Animals; D015152:Blotting, Northern; D002358:Cartilage, Articular / Q000276:immunology / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D006681:HLA-D Antigens / Q000276:immunology; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000502:physiology*; D007375:Interleukin-1 / Q000502:physiology*; D007700:Kinetics; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
D006681:HLA-D Antigens; D007375:Interleukin-1; D012333:RNA, Messenger; D007371:Interferon-gamma; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3