title: Capsaicin inhibits IFN-gamma-induced MHC class II expression by suppressing transcription of class II transactivator gene in murine peritoneal macrophages.
abstract: 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 (0.1-10microM) reduced the expression of MHC class II mRNA levels in cultured peritoneal macrophages upon treatment with interferon (IFN)-gamma (100units/ml). In agreement with this, treatment of the cells with capsaicin also inhibited MHC class II transactivator (CIITA) mRNA expression induced by IFN-gamma 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-gamma-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.
authors.affiliation: Department of Basic Veterinary Science, Laboratory of Physiology, The United Graduate School of Veterinary Sciences, Gifu University, Yanagido, Gifu, Japan.
authors.forename: Motamed Elsayed
authors.initials: ME
authors.lastname: Mahmoud
authors.forename: Hideki
authors.initials: H
authors.lastname: Nikami
authors.forename: Takahiko
authors.initials: T
authors.lastname: Shiina
authors.forename: Tadashi
authors.initials: T
authors.lastname: Takewaki
authors.forename: Yasutake
authors.initials: Y
authors.lastname: Shimizu
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017951:Antigen Presentation; D002211:Capsaicin / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D005802:Genes, MHC Class II / Q000187:drug effects / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D009569:Nitric Oxide; D007371:Interferon-gamma; D002211:Capsaicin