Abstract
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.
Highlights
P1integrin subunit can be combined to multiple a integrin subunits andform a setof heterodimeric cell surface receptors for laminin, fibronectin, and collagens
Integrins have an importantbiological role as mediatorsof cell matrix and in some cases cell-cell interaction [19]
Manyessentialaspects of cell behaviorlike migration, differentiation, and synthesis of certain proteins are under the control of extracellular matrix suggesting that the matrix receptorshave a signal transduction function
Summary
From the Departmentof Medical Biochemistry, University of Turku, SF-20.520 Turku, Finland. We show that two inflammatory mediators, interleukin-18 (IL-18) and tumor necrosis factor-a(TNF-a), can regulate the expression of the a l @ ,integrin heterodimer, known to bea laminin and collagen receptor. The effect of TNF-a on al subunit expression is similar Both IL-18 and TNF-a increased MG-63 cell adhesion on laminin. The effect of transforming growth factor-81 (TGF81) on integrin expression in MG-63 cells has been previously described We report that two inflammatory mediators, interleukin-lp(IL-la)andtumor necrosis factor-a (TNF-a) are potent regulators of a1integrin subunit expression. I The abbreviationsused are TGF, transforminggrowth factor;IL, interleukin; TNF, tumor necrosis factor; DMEM, Dulbecco’s modification of Eagle’s medium; FCS, fetal calf serum; PBS, phosphatebuffered saline; PG, prostaglandin;VLA, very late activation antigen.
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