Bacterial chemoattractant synergizes with LPS to induce inflammation via upregulating TLR4

The principal challenge for the host is to efficiently detect the invading pathogen and mount a rapid defensive response. Leukocytes recognize invading pathogens by directly interacting with pathogen-associated molecular patterns via Toll-like receptors (TLRs) expressed on the leukocyte surfaces. In the present study we show for the first time that fMLP synergized with LPS to induce an inflammatory response via up-regulation of TLR4 in vitro and in vivo. Moreover, we show that fMLP-induced TLR4 up-regulation was mediated by FPR and Gi/Go class of heterotrimeric G proteins. Interestingly, low molecular weight GTPase Rho A acted as a regulator for FPR-mediated TLR4 induction, thereby implying a critical role for Rho A GTPase in inflammatory response during bacterial infection. Our data indicate a possible important role of fMLP that bacterial chemoattractant fMLP not only attracts leukocytes but also contributes directly to inflammation by synergizing with bacterial LPS.