Analysis of the expression of intercellular adhesion molecule-1 in cells of the human bronchial epithelial cell line NCI-H292

The mechanism of the expression of intercellular adhesion molecule-1 (ICAM-1) on epithelial cells was analyzed using NCI-H292 cells, a human bronchial epithelial cell line. Treatment with interferon-gamma (100 U/ml) or the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA) (16.2 nM) induced ICAM-1 expression. The interferon-gamma-induced ICAM-1 expression was reduced by the tyrosine kinase inhibitor genistein (4'.5.7-trihydroxyisoflavone) (37 to 185 mu M), but not by the protein kinase C inhibitor Ro 31-8425 ((3-[8-(aminomethyl)-6.7.8.9-tetrahydropyrido [1.2-a]indol-10-yl]-4-(1-methyl-1 H-pyrrole-2,3-dione) (10 mu M). The TPA-induced ICAM-1 expression was reduced by the protein kinase C inhibitor Ro 31-5125 (1 to 10 mu M), but not by the tyrosine kinase inhibitor genistein (185 mu M). The protein kinase A inhibitor H-89, (N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide) did not affect the ICAM-1 expression induced by interferon-gamma or TPA. Pyrrolidine dithiocarbamate (1-pyrrolidinecarbodithioic acid) (100 mu M), an inhibitor of nuclear factor kappa B (NF-kappa B) activation enhanced the ICAM-1 expression induced by interferon-gamma, but reduced that induced by TPA. The changes in ICAM-1 expression on the cell surface were correlated with the changes in ICAM-1 mRNA levels. Combined treatment with interferon-gamma and TPA induced more than additive ICAM-1 expression. These findings suggest that interferon-gamma induces ICAM-1 expression by a tyrosine kinase-dependent mechanism, but that TPA induces it by a protein kinase C- and NF-kappa B-dependent mechanism. (C) 1998 Elsevier Science B.V.