An atypical Protein Kinase C (PKCζ) plays a critical role in lipopolysaccharide-activated NF-κB in human peripheral blood monocytes and macrophages

Xue Song Huang, Ling Yu Chen, Astrid M. Doerner, Warren W. Pan, Laura Smith, Shuang Huang, Thomas J. Papadimos, Zhixing K. Pan

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

We have reported that the bacterial LPS induces the activation of NF-κB 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, PKCζ, associates functionally with RhoA and that PKCζ acts as a signaling component downstream of RhoA. Stimulation of monocytes and macrophages with LPS resulted in PKCζ activation and that inhibition of PKCζ activity blocks both LPS-stimulated activation of NF-κB and IL-1β gene expression. Our results also indicate that transforming growth factor β-activated kinase 1 acts as a signaling component downstream of PKCζ 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/PKCζ/transforming growth factor β-activated kinase 1/NF-κB pathway in host defense and in proinflammatory cytokine synthesis induced by bacterial LPS.

Original languageEnglish (US)
Pages (from-to)5810-5815
Number of pages6
JournalJournal of Immunology
Volume182
Issue number9
DOIs
StatePublished - May 1 2009

Fingerprint

Protein Kinase C
Lipopolysaccharides
Monocytes
Macrophages
Transforming Growth Factors
Cytokines
Phosphotransferases
rhoA GTP-Binding Protein
Gene Expression
rho GTP-Binding Proteins
Monomeric GTP-Binding Proteins
Interleukin-1
Isoenzymes
PKC-3 protein
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

An atypical Protein Kinase C (PKCζ) plays a critical role in lipopolysaccharide-activated NF-κB in human peripheral blood monocytes and macrophages. / Huang, Xue Song; Chen, Ling Yu; Doerner, Astrid M.; Pan, Warren W.; Smith, Laura; Huang, Shuang; Papadimos, Thomas J.; Pan, Zhixing K.

In: Journal of Immunology, Vol. 182, No. 9, 01.05.2009, p. 5810-5815.

Research output: Contribution to journalArticle

Huang, Xue Song ; Chen, Ling Yu ; Doerner, Astrid M. ; Pan, Warren W. ; Smith, Laura ; Huang, Shuang ; Papadimos, Thomas J. ; Pan, Zhixing K. / An atypical Protein Kinase C (PKCζ) plays a critical role in lipopolysaccharide-activated NF-κB in human peripheral blood monocytes and macrophages. In: Journal of Immunology. 2009 ; Vol. 182, No. 9. pp. 5810-5815.
@article{272811265fc74c029bb226b7c2fd4b34,
title = "An atypical Protein Kinase C (PKCζ) plays a critical role in lipopolysaccharide-activated NF-κB in human peripheral blood monocytes and macrophages",
abstract = "We have reported that the bacterial LPS induces the activation of NF-κB 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, PKCζ, associates functionally with RhoA and that PKCζ acts as a signaling component downstream of RhoA. Stimulation of monocytes and macrophages with LPS resulted in PKCζ activation and that inhibition of PKCζ activity blocks both LPS-stimulated activation of NF-κB and IL-1β gene expression. Our results also indicate that transforming growth factor β-activated kinase 1 acts as a signaling component downstream of PKCζ 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/PKCζ/transforming growth factor β-activated kinase 1/NF-κB pathway in host defense and in proinflammatory cytokine synthesis induced by bacterial LPS.",
author = "Huang, {Xue Song} and Chen, {Ling Yu} and Doerner, {Astrid M.} and Pan, {Warren W.} and Laura Smith and Shuang Huang and Papadimos, {Thomas J.} and Pan, {Zhixing K.}",
year = "2009",
month = "5",
day = "1",
doi = "10.4049/jimmunol.0804073",
language = "English (US)",
volume = "182",
pages = "5810--5815",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "9",

}

TY - JOUR

T1 - An atypical Protein Kinase C (PKCζ) plays a critical role in lipopolysaccharide-activated NF-κB in human peripheral blood monocytes and macrophages

AU - Huang, Xue Song

AU - Chen, Ling Yu

AU - Doerner, Astrid M.

AU - Pan, Warren W.

AU - Smith, Laura

AU - Huang, Shuang

AU - Papadimos, Thomas J.

AU - Pan, Zhixing K.

PY - 2009/5/1

Y1 - 2009/5/1

N2 - We have reported that the bacterial LPS induces the activation of NF-κB 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, PKCζ, associates functionally with RhoA and that PKCζ acts as a signaling component downstream of RhoA. Stimulation of monocytes and macrophages with LPS resulted in PKCζ activation and that inhibition of PKCζ activity blocks both LPS-stimulated activation of NF-κB and IL-1β gene expression. Our results also indicate that transforming growth factor β-activated kinase 1 acts as a signaling component downstream of PKCζ 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/PKCζ/transforming growth factor β-activated kinase 1/NF-κB pathway in host defense and in proinflammatory cytokine synthesis induced by bacterial LPS.

AB - We have reported that the bacterial LPS induces the activation of NF-κB 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, PKCζ, associates functionally with RhoA and that PKCζ acts as a signaling component downstream of RhoA. Stimulation of monocytes and macrophages with LPS resulted in PKCζ activation and that inhibition of PKCζ activity blocks both LPS-stimulated activation of NF-κB and IL-1β gene expression. Our results also indicate that transforming growth factor β-activated kinase 1 acts as a signaling component downstream of PKCζ 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/PKCζ/transforming growth factor β-activated kinase 1/NF-κB pathway in host defense and in proinflammatory cytokine synthesis induced by bacterial LPS.

UR - http://www.scopus.com/inward/record.url?scp=66949151788&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66949151788&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.0804073

DO - 10.4049/jimmunol.0804073

M3 - Article

C2 - 19380829

AN - SCOPUS:66949151788

VL - 182

SP - 5810

EP - 5815

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 9

ER -