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.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center, Washington, DC 20037.
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D000470:Alkaloids / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014471:Umbilical Veins
D000470:Alkaloids; D007375:Interleukin-1; D011994:Recombinant Proteins; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium