The surface glycoprotein intercellular adhesion molecule-1 (ICAM-1) mediates important immunologic cell interactions during cutaneous inflammatory processes by binding to the leukocyte integrin lymphocyte function-associated antigen-1. The expression of ICAM-1 is induced in epidermal keratinoeytes by certain pro-inflammatory stimuli, and this modulation is transcriptionally regulated. To identify the molecular mechanisms involved in the regulation of 1CAMA gene expression, we have previously cloned tile transcriptional regulatory region of the human ICAM-1-gene and have characterized a functional promoter. Here we have used the phorbol ester phorbol-12-myristate-13-acetate (PMA) to further evaluate the transcriptional mechanisms of ICAM-1 gene induction in A431 cells. Exposure to PMA induced ICAM-1 both at the mRNA and cell surface level. Promoter activity and PMA-enhanced effects were assessed by transiently transfecting A431 cells with chloramphenicol acetyl transferase reporter gene constructs containing a series of sequential JCAM-1 5' deletions. Constructs containing ICAM1 5' fragments from -1162/+1 (relative to the transcription start site) to -277/+ 1 displayed a threefold increase in promoter activity when cells were stimulated with PMA. Inducibility dropped below 1.5-fold in chloramphenicol acetyl transferase construct -182/+1. Using electrophoretic mobility shift assays, a PMA- inducible binding site was identified for an NFκB-like complex within positions -186/-177, A -199/-170 fragment containing this NFκB-like element conferred PMA responsiveness when cloned into a thymidine kinase-driven chloramphenicol acetyl transferase vector, indicating that the region containing this NFκB-like element is not only necessary but also sufficient for PMA induction of JCAMA. [ABSTRACT FROM AUTHOR]