Influence of ion channel modulation on in vitro interferon-gamma induced MHC class I and II expression on macrophages.
The in vitro effect of K+ channel blockers quinidine and verapamil, anion channel blocker SITS and K+ channel openers diazoxide, pinacidil, and BRL 38227 on interferon-gamma (IFN-gamma) induced MHC class I and II expression of Lewis rat peritoneal macrophages was investigated by cell ELISA assay. MHC class I expression was significantly enhanced by diazoxide at concentrations of 10(-5)M to 10(-6)M and by pinacidil and BRL 38227 at the concentration of 10(-6)M. MHC class II expression was enhanced by pinacidil and BRL 38227 at concentrations of 10(-5)M to 10(-6)M. The enhancing effect of pinacidil could be blocked by inhibitors of the protein kinases PKA and PKC suggesting that activation of both is required for optimum induction of MHC molecule expression. K+ and anion channel blockers were less active in modulation of MHC molecule expression. Verapamil had no influence, quinidine suppressed MHC class I expression at concentrations of 10(-4)M to 10(-5)M, and SITS suppressed MHC class I expression at the concentration of 10(-3)M. Since MHC class II expression is essential for efficient antigen presentation to T helper cells and MHC class I expression is required for target cell lysis by cytotoxic T cells, ion channel modulating drugs may be potential candidates for immunopharmacological intervention in inflammatory diseases.
Zhu
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Department of Neurology, Karolinska Institute, Huddinge University Hospital, Sweden.
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Olsson
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D000818:Animals; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007473:Ion Channels; D007371:Interferon-gamma