Retinoic acid potentiates TNF-alpha-induced ICAM-1 expression in normal human epidermal keratinocytes

ICAM-1 protein in keratinocytes is thought to contribute to cutaneous infla mmatory reactions. Its induction depends-among others-on cytokines such as TNF-alpha, IFN-gamma, IL-1 or on retinoic acid (RA), a key regulator of epi dermal homeostasis. We investigated the effect of treatments with TNF-alpha , RA or their combination on ICAM-1 expression on proliferative or differen tiating keratinocytes over an 8 day culture period. Basal ICAM-1 levels wer e undetectable at low (30 mu M) and standard (88 mu M) Ca2+ and RA alone di d not induce ICAM-1. However, at high Ca2+ (1500 mu M), ICAM-1 levels were augmented in response to RA-treatment. TNF-alpha induced a transient ICAM-1 increase in NHK, which reached peak-levels 2-4 days post cytokine stimulus . RA. potentiated the TNF-alpha-induced ICAM-1 response in all Ca2+-concent rations. This potentiating effect of RA was confirmed at the mRNA level. In summary, our results establish retinoic acid as an enhancer of TNF-alpha-i nduced ICAM-1 levels in NHK, (C) 1999 Academic Press.