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 endothelial cell proliferation. The present experiments demonstrate that IL-1 alpha can also suppress gap junction activity as measured by dye-coupling assays on human umbilical vein endothelial cells (HUVEC). 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-myristate 13-acetate. Interestingly, IL-1 alpha was not effective in reducing cell communication in senescent HUVEC which exhibit lower coupling than early-passage cells and for which elevated levels of IL-1 alpha transcript and polypeptide had been reported previously. These results suggest a novel role for IL-1 alpha in the regulation of intercellular communication, which may be related to its role as a regulator of endothelial differentiation and senescence.