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

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.

► Poly (I:C) regulate histamine responses in human gingival fibroblast. ► Poly (I:C) down-regulates calcium mobilization to inhibit histamine responses. ► Poly (I:C) effect is dependent on the phosphorylation of PKCα. ► We proved that Poly (I:C) could attenuate expression and synthesis of COX-2.