An atypical protein kinase C (PKC zeta) plays a critical role in lipopolysaccharide-activated NF-kappa B in human peripheral blood monocytes and macrophages.
We have reported that the bacterial LPS induces the activation of NF-kappaB 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, PKCzeta, associates functionally with RhoA and that PKCzeta acts as a signaling component downstream of RhoA. Stimulation of monocytes and macrophages with LPS resulted in PKCzeta activation and that inhibition of PKCzeta activity blocks both LPS-stimulated activation of NF-kappaB and IL-1beta gene expression. Our results also indicate that transforming growth factor beta-activated kinase 1 acts as a signaling component downstream of PKCzeta 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/PKCzeta/transforming growth factor beta-activated kinase 1/NF-kappaB pathway in host defense and in proinflammatory cytokine synthesis induced by bacterial LPS.
Huang
XueSong
X
Department of Medical Microbiology & Immunology, University of Toledo Medical Center, Toledo, OH 43614, USA.
Chen
Ling-Yu
LY
Doerner
Astrid M
AM
Pan
Warren W
WW
Smith
Laura
L
Huang
Shuang
S
Papadimos
Thomas J
TJ
Pan
Zhixing K
ZK
D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D008070:Lipopolysaccharides / Q000502:physiology*; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism*; D016328:NF-kappa B / Q000097:blood / Q000378:metabolism*; D011493:Protein Kinase C / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D000099221:Protein Kinase C zeta
D007527:Isoenzymes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta