Synergy of TLR2 and H1R on Cox-2 Activation in Pulpal Cells

Although pulp fibroblasts are a major cell type in dental pulp, their roles in microbial recognition and pulpal inflammation are not well-understood. Considering the pivotal role of Toll-like receptors (TLRs) in the recognition of micro-organisms, we hypothesized that TLRs on pulp fibroblasts may induce inflammatory signals in dental pulp. In human pulp fibroblasts, TLR2, 3, 4, and 5 were constitutively expressed. Stimulation of TLR2 and 3 induced the expression of pro-inflammatory genes such as CXCL10, CCL5, and/or Cox-2 in pulp fibroblasts. Interestingly, histamine synergistically activated TLR2-mediated Cox-2 expression and PGE(2) production. The synergistic effect of histamine is mediated by histamine receptor-1 (H1R). Studies on the intracellular signaling pathways revealed that p38 activation is required for the synergistic activation of Cox-2 by TLR2 and histamine. Analysis of these data suggests that TLR2 on pulp fibroblasts, in concert with H1R, can induce an inflammatory response during microbial infection in dental pulp. Abbreviations: Toll-like receptors (TLRs), histamine receptor-1 (H1R), PGE 2 (prostaglandin E 2), CPR (chlorpheniramine), Cox-2 (cyclooxygenase-2).