Capsaicin inhibits IFN-γ-induced MHC class II expression by suppressing transcription of class II transactivator gene in murine peritoneal macrophages

Major histocompatibility complex (MHC) class II molecules play crucial roles in adaptive immune response and antigen presentation. Owing to enlargement of capsaicin's availability as an anti-inflammatory agent in medical therapeutics, we investigated the new effects of capsaicin that are related to adaptive immune response in terms of MHC class II expression in murine primary cultured macrophages. Capsaicin (0.1–10 µM) reduced the expression of MHC class II mRNA levels in cultured peritoneal macrophages upon treatment with interferon (IFN)-γ (100 units/ml). In agreement with this, treatment of the cells with capsaicin also inhibited MHC class II transactivator (CIITA) mRNA expression induced by IFN-γ in a dose-dependent manner. In contrast, production of nitric oxide, which has the ability to reduce MHC class II expression, was not enhanced but rather suppressed by capsaicin treatment in IFN-γ-stimulated macrophages. These findings suggest that capsaicin suppresses expression of MHC class II via downregulation of CIITA transcription but not through the mediation of nitric oxide production by macrophages. These new immunopharmacological roles of capsaicin in specific transcription regulation of genes involved in antigen presentation of macrophages could be useful for the treatment of adaptive immune-mediated disorders.