Interferon-gamma-induced HLA-DR, but not ICAM-1, expression of human keratinocytes is down-regulated by calmodulin antagonist.
Interferon-gamma (IFN-gamma) 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-gamma 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-gamma. We found that the IFN-gamma-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-gamma-induced HLA-DR, but not ICAM-1, expression is mediated, if not exclusively, by calmodulin in human KC.
Saitoh
A
A
Department of Dermatology, Yamanashi Medical University, Japan.
Osada
A
A
Kitajima
Y
Y
Furue
M
M
Tamaki
K
K
D002147:Calmodulin / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006684:HLA-DR Antigens / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D015603:Keratinocytes / Q000378:metabolism*; D015203:Reproducibility of Results; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D002147:Calmodulin; D006684:HLA-DR Antigens; D013449:Sulfonamides; D018799:Intercellular Adhesion Molecule-1; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D007371:Interferon-gamma