ALPHA-6.BETA-1 INTEGRIN (LAMININ RECEPTOR) IS DOWN-REGULATED BY TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1 BETA IN HUMAN ENDOTHELIAL-CELLS

Endothelial cells from human umbilical vein (HEC) express several distinct integrin complexes that mediate the interaction with the basal membrane components. In this paper we show that treatment with tumor necrosis factor-alpha (TNF-alpha) down-regulates the expression of the laminin receptor alpha-6.beta-1 integrin in cultured HEC. After 48 h of treatment with TNF-alpha, the level of expression of the alpha-6.beta-1 complex reached 20% of the control value. The down-regulation of the alpha-6.beta-1 integrin is caused by a decreased expression of the alpha-6 subunit, whereas the synthesis of the beta-1 subunit remains constant. Northern blot analysis shows that the decreased level of alpha-6 subunit synthesis is caused by down-regulation of alpha-6 mRNA in TNF-alpha-treated HEC. TNF-alpha treatment does not alter the expression of alpha-2, alpha-3, and alpha-5 integrins, also present on endothelial cell surface, thus showing that this cytokine has a selective action on distinct integrin complexes. Down-regulation of alpha-6.beta-1 correlates with pronounced reduction in adhesion of TNF-alpha-treated HEC to laminin, but not to fibronectin-coated culture dishes. In addition to TNF-alpha, interleukin-1-beta also decreases the expression of the alpha-6.beta-1 integrin and reduces adhesion to laminin, thus suggesting that this regulation plays an important role in inflammation.