Down-regulation of protein kinase C: A potential mechanism for 2-amino-3-methylimidazo[4,5-f]quinoline-mediated immunosuppression

Immunosuppressive mechanism of food-born mutagenic and carcinogenic heterocyclic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), was studied in murine spleen cells. IQ suppressed the IL-2 secretion and its mRNA expression. Treatment of IQ also decreased PKC activity in both the membrane fraction and the cytosol fraction. Treatment of PMA resulted in the recovery of IQ-induced suppression of IL-2 production, but the addition of ionomycin (Io) had no effect. Subsequently, we examined the effect of IQ on the activation of NF-κB, AP-1, and NF-AT, which are key transcription factors for IL-2 transcription. The activation of NF-κB and AP-1 was markedly inhibited by IQ in PMA/PHA-stimulated cells. Meanwhile, NF-AT was not affected by IQ in PMA/Io-stimulated cells. These results suggest that the immunosuppression induced by IQ might be associated with the down-regulation of PKC and subsequent blockade of the activation of NF-κB and AP-1 in the IL-2 gene expression. Copyright (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.