INTERLEUKIN-1-ALPHA SUPPRESSES GAP JUNCTION-MEDIATED INTERCELLULAR COMMUNICATION IN HUMAN ENDOTHELIAL-CELLS

Interleukin-1 alpha (IL-1 alpha) is a potent modulator of endothelial cell-surface properties and function as well as an inhibitor of endoth elial cell proliferation. The present experiments demonstrate that IL- 1 alpha r can also suppress gap junction activity as measured by dye-c oupling assays on human umbilical vein endothelial cells (HU-VEC). The effect of IL-1 alpha is dose- and time-dependent, inhibitable by IL-1 receptor antagonist, independent of changes in intracellular [Ca+2], and distinguishable from the short-term effects of phorbol 12-myristat e 13-acetate. Interestingly, IL-1 alpha was not effective in reducing cell communication in senescent HUVEC which exhibit lower coupling tha n early-passage cells and for which elevated levels of IL-1 alpha tran script and polypeptide had been reported previously. These results sug gest a novel role for IL-1 alpha in the regulation of intercellular co mmunication, which may be related to its role as a regulator of endoth elial differentiation and senescence. (C) 1994 Academic Press, Inc.