Davanian H, Båge T, Lindberg J, Lundeberg J, Concha HQ, Sällberg Chen M, Yucel-Lindberg T
Cytokine 57 (3) 406-416 [2012-03-00; online 2012-01-05]
Periodontitis is a chronic inflammatory disease characterized by a host inflammatory response against bacteria that leads to destruction of the supporting structures of the teeth. Bacterial components of pathogens in the periodontal pocket are recognized by toll-like receptors (TLRs) that trigger an inflammatory response. In this study, we investigated the effects of the pro-inflammatory cytokine tumor necrosis factor α (TNFα) on TLR2 expression in human gingival fibroblasts. In addition, we examined the signaling pathways involved in the regulation of TNFα-induced TLR2 expression. Our results showed that TNFα increased TLR2 mRNA and protein expression. Microarray analysis and the inhibition of specific signaling pathways demonstrated that c-Jun N-terminal kinases (JNK) and nuclear factor kappa B (NF-κB) were involved in the regulation of TNFα-induced TLR2 expression in gingival fibroblasts. Furthermore, the prostaglandin E(2) (PGE(2)) regulatory enzyme cytosolic phospholipase A(2) (cPLA(2)) and the anti-inflammatory prostaglandin 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)), were found to regulate TLR2 mRNA expression stimulated by TNFα. Our findings suggest that these pathways and mediators, through the regulation of TLR2 expression in gingival fibroblasts, may be involved in the pathogenesis of periodontitis. The study provides new insights into the molecular mechanisms underlying the regulation of TLR2, implicated in the chronic inflammatory disease periodontitis.