Activation of Toll-like receptor 2 induces B 1 and B 2 kinin receptors in human gingival fibroblasts and in mouse gingiva

The regulation of the kallikrein-kinin system is an important mechanism controlling vasodilation and promoting inflammation. We aimed to investigate the role of Toll-like receptor 2 (TLR2) in regulating kinin B 1 and B 2 receptor expression in human gingival fibroblasts and in mouse gingiva. Both P. gingivalis LPS and the synthetic TLR2 agonist Pam 2 CSK 4 increased kinin receptor transcripts. Silencing of TLR2, but not of TLR4, inhibited the induction of kinin receptor transcripts by both P. gingivalis LPS and Pam 2 CSK 4 . Human gingival fibroblasts (HGF) exposed to Pam 2 CSK 4 increased binding sites for bradykinin (BK, B 2 receptor agonist) and des-Arg 10 -Lys-bradykinin (DALBK, B 1 receptor agonist). Pre-treatment of HGF for 24 h with Pam 2 CSK 4 resulted in increased PGE 2 release in response to BK and DALBK. The increase of B1 and B2 receptor transcripts by P. gingivalis LPS was not blocked by IL-1β neutralizing antibody; TNF-α blocking antibody did not affect B 1 receptor up-regulation, but partially blocked increase of B 2 receptor mRNA. Injection of P. gingivalis LPS in mouse gingiva induced an increase of B 1 and B 2 receptor mRNA. These data show that activation of TLR2 in human gingival fibroblasts as well as in mouse gingival tissue leads to increase of B 1 and B 2 receptor mRNA and protein.