Regulation of integrin-type cell adhesion receptors by cytokines.
Integrin heterodimers which share a common beta 1 subunit are the major cellular receptors for many extracellular matrix proteins. Here, we show that two inflammatory mediators, interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), can regulate the expression of the alpha 1 beta 1 integrin heterodimer, known to be a laminin and collagen receptor. In human skin fibroblasts 10 units/ml IL-1 beta increase the biosynthesis of the alpha 1 integrin subunit an average of 4.5-fold. Furthermore, IL-1 beta can turn on alpha 1 subunit expression in MG-63 human osteosarcoma cells even in conditions where the untreated MG-63 cells do not express it in detectable amounts. The effect of TNF-alpha on alpha 1 subunit expression is similar. Both IL-1 beta and TNF-alpha increased MG-63 cell adhesion on laminin. The effect of transforming growth factor-beta 1 (TGF-beta 1) on integrin expression in MG-63 cells has been previously described (Heino, J., and Massagué, J. (1989) J. Biol. Chem. 264, 21806-21811). TGF-beta 1 decreases the biosynthesis of alpha 3 subunit but increases the production of alpha 2 subunit. IL-1 beta potentiates the effects of TGF-beta 1. Furthermore, in the presence of TGF-beta 1 the increase in the expression of alpha 1 subunit by IL-1 beta is even larger. Thus, IL-1 beta and TGF-beta 1, which usually have antagonistic functions in connective tissue, can regulate integrin expression in a synergistic way.
Santala
P
P
Department of Medical Biochemistry, University of Turku, Finland.
Heino
J
J
D002448:Cell Adhesion; D002452:Cell Count; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D016023:Integrins / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D007797:Laminin / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D016023:Integrins; D007375:Interleukin-1; D007797:Laminin; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone; D007213:Indomethacin