RhoA and Rac1 signals in fMLP-induced NF-kappaB activation in human blood monocytes.

ABSTRACT

GTPase RhoA is required for fMet-Leu-Phe (fMLP)-stimulated NF-kappaB activation in human peripheral blood monocytes. Here we have investigated different members of the Rho family of GTPases Rac1, Cdc42, and RhoA in regulating the transcription factor nuclear factor-kappaB (NF-kappaB) in human peripheral blood monocytes. Stimulation of monocytes with fMLP rapidly activated Rac1, Cdc42, and RhoA and cotransfection of the monocytic THP1 cells with dominant negative forms of Rho GTPases, we found that Rac1 and RhoA, but not Cdc42, involved fMLP-stimulated kappaB reporter gene expression. These results indicate that fMLP stimulates three members of the Rho family of GTPases Rac1, Cdc42, and RhoA activity in monocytes, and that Rac1 and RhoA, but not Cdc42, is required for fMLP-induced NF-kappaB activation. Furthermore, our data also suggest that RhoA is mediated by signals independent of Rac1 in NF-kappaB activation in human peripheral blood monocytes stimulated with bacterial products.