1α,25-dihydroxyvitamin D3 modulates Ia antigen expression induced by interferon-γ and prostaglandin E2 production in Pam 212 cells

Recent investigations suggest that 1α,25-dihydroxyvitamin D₃ [1α,25(OH)₂D₃] has an effect on the regulation of immune responses and that keratinocyte (KC) expression of major histocompatibility complex class II antigens may be involved in immune responses. We investigated the modulation by 1α,25(OH)₂D₃ of Ia antigen expression induced by interferon-γ (IFN-γ) and prostaglandin E₂ (PGE₂) production in Pam 212 cells. 1α,25(OH)₂D₃ at 10^?6, 10^?8 or 10^?10m significantly decreased the levels of IFN-γ-induced Ia antigen expression in Pam 212 cells. Pam 212 cells produced PGE₂ and 1α,25-(OH)₂D₃ enhanced Pam 212 cell PGE₂ production. However, indomethacin (1, 5 and 10 μg/ml) did not abrogate the inhibitory effect of 1α,25(OH)₂D₃ on IFN-γ induction of Ia antigen expression in Pam 212 cells, indicating that the products of the cyclo-oxygenase pathway do not mediate 1α,25(OH)₂D₃ inhibition of IFN-γ induction of Pam 212 cell Ia antigen expression. Our studies suggest that in Pam 212 cells the levels of Ia antigen expression induced by IFN-γ and PGE₂ production are negatively and positively regulated by 1α,25(OH)₂D₃, respectively, and that 1α,25(OH)₂D₃ may play a role in the regulation of immune responses.