title: The effects of histamine on interferon gamma production are dependent on the stimulatory signals.
abstract: Histamine regulates the immune response by enhancing TH2 cytokine production and by inhibiting TH1 cytokine production. We assessed the mechanisms of histamine's action on helper T cell subsets by evaluating the role of protein kinase A (PKA) in the histamine-mediated effects on IFN gamma production. The splenocytes and TH1 murine cloned cells (pGL10) were pretreated with histamine at a concentration range of 10(-8)-10(-5) M for 1 h and then were activated with anti-CD3, PHA, PMA + ionomycin, or ionomycin for 24 h. The levels of IFN gamma were measured in the supernatants by ELISA. The inhibitory effects of histamine were the most prominent in anti-CD3-stimulated splenocytes (61%). The effects of histamine on IFN gamma production from TH1 cells depended on the mode of cell activation. The activation of cells with anti-CD3 resulted in 27% inhibition of IFN gamma production whereas the activation with ionomycin produced 70% suppression. The inhibitory effects of histamine were completely reversed by cimetidine in a dose-dependent manner in both TH1 cells and in splenocytes. PKA played a role in the inhibition of IFN gamma by histamine when the cells were activated via TCR, and the PKA inhibitors Rp-cAMPS (10(-5) M) and H8 (10(-5) M) reversed the inhibitory effects of histamine on IFN gamma production. However, when the cells were stimulated with ionomycin, the PKA inhibitors did not affect histamine-mediated suppression of IFN gamma production.
authors.affiliation: Department of Pharmaceutical and Administrative Sciences, Creighton University, Omaha, NE, 68178, USA.
authors.forename: N
authors.initials: N
authors.lastname: Osna
authors.forename: K
authors.initials: K
authors.lastname: Elliott
authors.forename: M M
authors.initials: MM
authors.lastname: Khan
mesh_terms: D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002999:Clone Cells; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D008806:Mice, Inbred AKR; D008811:Mice, Inbred DBA; D018417:Th1 Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology
chemical_list: D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D003994:Bucladesine; D006632:Histamine; D007371:Interferon-gamma; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases