Interferon-γ-induced HLA-DR, but not ICAM-1, expression of human keratinocytes is down-regulated by calmodulin antagonist

Interferon-γ (IFN-γ) has been shown to induce or enhance the expression of MHC class II and intercellular adhesion molecule-1 (ICAM-1) in a variety of human and murine cell types, including epidermal keratinocytes (KC). However, the expression of MHC class II and ICAM-1 molecules induced by IFN-γ is not necessarily coordinated. We investigated the inhibitory effects of the calmodulin antagonist, W-7, and its chlorine deficient inactive analogue, W-5, on the expression of MHC class II (HLA-DR) and ICAM-1 by human KC incubated with IFN-γ. We found that the IFN-γ-induced expression of HLA-DR was reproducibly and dose-dependently inhibited by W-7. However, the expression of ICAM-1 was highly resistant to the inhibitory effects of W-7. Neither HLA-DR nor ICAM-1 expression was affected by W-5. These data suggest that the IFN-γ-induced HL-LDR, but not ICAM-1, expression-is mediated, if not exclusively, by calmodulin in human KC.