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

36 Scopus citations

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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