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 and B receptor expression in human gingival fibroblasts and in mouse gingiva. Both P. gingivalis LPS and the synthetic TLR2 agonist Pam CSK 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 CSK . Human gingival fibroblasts (HGF) exposed to Pam CSK increased binding sites for bradykinin (BK, B receptor agonist) and des-Arg -Lys-bradykinin (DALBK, B receptor agonist). Pre-treatment of HGF for 24 h with Pam CSK resulted in increased PGE 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 receptor up-regulation, but partially blocked increase of B receptor mRNA. Injection of P. gingivalis LPS in mouse gingiva induced an increase of B and B 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 and B receptor mRNA and protein.