TUMOR NECROSIS FACTOR-ALPHA-STIMULATED AND INTERLEUKIN-1-STIMULATED INTERCELLULAR-ADHESION MOLECULE-1 EXPRESSION BY MURINE RENAL TUBULAR EPITHELIAL-CELLS IS TRANSCRIPTIONALLY REGULATED AND INVOLVES PROTEIN-KINASE-C

The regulation of intercellular adhesion molecule-1 (ICAM-1) expression by renal tubular epithelial cells (TEC) has been studied in vitro. ICAM-1 expression in TEC is stimulated with phorbol 12-myristate 13-acetate (PMA), but not with forskolin, suggesting a role for protein kinase C (PKC) but not for protein kinase A (PKA). The tumor necrosis factor-alpha- (TNF-alpha and interleukin-1 (IL-1)-stimulated ICAM-1 expression in TEC is blocked with the PKC/PKA inhibitor staurosporine, and also with the PKC-selective inhibitor calphostin C. The TNF-alpha-stimulated ICAM-1 expression is resistant however to downregulation of PKC with PMA. The TNF-alpha- and IL-1-stimulated ICAM-1 expression is also inhibited with the transcriptional inhibitor actinomycin D and with the protein synthesis inhibitor cycloheximide. Thus, ICAM-1 expression by TEC may involve a downregulation-resistant PKC which induces ICAM-1 expression at a transcriptional level.