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

Recent investigations suggest that 1 alpha,25-dihydroxyvitamin D3 [1 alpha,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 1 alpha,25(OH)2D3 of Ia antigen expression induced by interferon-gamma (IFN-gamma) and prostaglandin E2 (PGE2) production in Pam 212 cells. 1 alpha,25(OH)2D3 at 10(-6), 10(-8) or 10(-10) M significantly decreased the levels of IFN-gamma-induced Ia antigen expression in Pam 212 cells. Pam 212 cells produced PGE2 and 1 alpha,25-(OH)2D3 enhanced Pam 212 cell PGE2 production. However, indomethacin (1, 5 and 10 micrograms/ml) did not abrogate the inhibitory effect of 1 alpha,25(OH)2D3 on IFN-gamma induction of Ia antigen expression in Pam 212 cells, indicating that the products of the cyclo-oxygenase pathway do not mediate 1 alpha,25(OH)2D3 inhibition of IFN-gamma 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-gamma and PGE2 production are negatively and positively regulated by 1 alpha,25(OH)2D3, respectively, and that 1 alpha,25(OH)2D3 may play a role in the regulation of immune responses.