title: Toll-like receptor 3 activation promotes desensitization of histamine response in human gingival fibroblasts: Poly (I:C) induces histamine receptor desensitization in human gingival fibroblasts.
abstract: Viruses are associated with the development of periodontal disease, particularly during periods of suppressed cellular immunity. For this reason, we evaluated the hypothesis that viral components regulate the actions of histamine, an important mediator of immune responses. We assessed the effect of Poly (I:C) on histamine-mediated intracellular calcium mobilization in human gingival fibroblasts. Our results show that histamine induces an increase in intracellular calcium concentrations in a dose-dependent manner. This response was blocked when cells were incubated in the presence of Poly (I:C). In addition, phorbol esters, a diacylglycerol analog, mimics the inhibitory actions of Poly (I:C) in response to histamine. The effect of Poly (I:C) was reversed by Stuarosporine (1 μM), GÖ6983 (7 μM), Bisindolylmaleimide (1 μM) [a protein inhibitor (PKC)], and SB 203580 (3 μM) (a p38-MAPK inhibitor). These findings suggest that Poly (I:C) regulates histamine-induced calcium mobilization through activation of PKC and p38.
authors.affiliation: Laboratorio de Bioquímica División de Estudios de Posgrado e Investigación, Facultad de Odontología, Universidad Nacional Autónoma de México, Mexico. gloria@fo.odonto.unam.mx
authors.forename: Gloria
authors.initials: G
authors.lastname: Gutiérrez-Venegas
authors.forename: Citlalli Ekaterina
authors.initials: CE
authors.lastname: Rodríguez-Pérez
mesh_terms: D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005881:Gingiva / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D010766:Phosphorylation; D011070:Poly I-C / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011968:Receptors, Histamine / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D051196:Toll-Like Receptor 3 / Q000276:immunology / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D007211:Indoles; D008301:Maleimides; D047428:Protein Kinase Inhibitors; D011968:Receptors, Histamine; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D006632:Histamine; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; C088060:bisindolylmaleimide; D013755:Tetradecanoylphorbol Acetate; D011070:Poly I-C; D002118:Calcium