An Atypical Protein Kinase C (PKCζ) Plays a Critical Role in Lipopolysaccharide-Activated NF-κB in Human Peripheral Blood Monocytes and Macrophages

We have reported that the bacterial LPS induces the activation of NF-kappa B and inflammatory cytokine gene expression and that this requires the activity of small GTPase, RhoA. In this study, we show that an atypical protein kinase C isozyme, PKC zeta associates functionally with RhoA and that PKC zeta acts as a signaling component downstream of RhoA. Stimulation of monocytes and macrophages with LPS resulted in PKC zeta activation and that inhibition of PKC zeta activity blocks both LPS-stimulated activation of NF-kappa B and IL-1 beta gene expression. Our results also indicate that transforming growth factor P-activated kinase 1 acts as a signaling component downstream of PKC zeta in cytokine gene transcription stimulated by LPS in human peripheral blood monocytes and macrophages. The specificity of this response suggests an important role for the Rho GTPase/PKC zeta/transforming growth factor beta-activated kinase 1/NF-kappa B pathway in host defense and in proinflammatory cytokine synthesis induced by bacterial LPS. The Journal of Immunology, 2009, 182: 5810-5815.