2-amino-3-methylimidazo[4,5-f]quinoline-mediated immunosuppression involves inhibition of protein kinase C in murine splenocytes

The effects of the food-borne mutagenic and carcinogenic heterocyclic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), on the proliferation of murine spleen cells was examined. A significant and dose-related suppression of the proliferative response to concanavalin A (Con A) was observed by the treatment of IQ. IQ also decreased markedly the level of proliferative response induced by PMA and ionomycin and the IL-2 secretion by T cells. Treatment of PMA resulted in the recovery of IQ-induced suppression of IL-2 production, but the addition of ionomycin (Io) had no effect, IQ decreased PKC activity in both the membrane fraction and the cytosol fraction and inhibited the phosphorylation of MARCKS protein. These results suggest that the suppression of spleen cell proliferation induced by IQ might be associated with the inhibition of PKC activity and the subsequent IL-2 secretion of T cells.