Synergistic activation of NF-κB by bacterial chemoattractant and TNFα is mediated by p38 MAPK-dependent RelA acetylation

Warren W. Pan, Jain Dong Li, Shuang Huang, Thomas J. Papadimos, Zhixing K. Pan, Ling Yu Chen

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

In the host immune system, leukocytes are often exposed to multiple inflammation inducers. NF-κB is of considerable importance in leukocyte function because of its ability to activate the transcription of many proinflammatory immediate-early genes. Tremendous efforts have been made toward understanding how NF-κB is activated by various inducers. However, most research on NF-κB regulation has been focused on understanding how NF-κB is activated by a single inducer. This is unlike the situation in the human immune system where multiple inflammation inducers, including both exogenous and endogenous mediators, are present concurrently. We now present evidence that the formylated peptide f-Met-Leu-Phe (fMLP), a bacterial chemoattractant, synergizes with TNFα to induce NF-κB activation and the resultant inflammatory response in vitro and in vivo. The mechanism of synergistic activation of NF-κB by bacterial fMLP and TNFα may be involved in the induction of RelA acetylation, which is regulated by p38 MAPK. Thus, this study provides direct evidence for the synergistic induction of NF-κB-dependent inflammatory responses by both exogenous and endogenous inducers. The ability of fMLP to synergize with TNFα and activate NF-κB represents a novel and potentially important mechanism through which bacterial fMLP not only attracts leukocytes but also directly contributes to inflammation by synergizing with the endogenous mediator TNFα.

Original languageEnglish (US)
Pages (from-to)34348-34354
Number of pages7
JournalJournal of Biological Chemistry
Volume285
Issue number45
DOIs
StatePublished - Nov 5 2010

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methionyl-leucyl-phenylalanine
Acetylation
Immune system
Chemotactic Factors
p38 Mitogen-Activated Protein Kinases
Chemical activation
Leukocytes
Transcription
Inflammation
Immune System
Genes
Peptides
Immediate-Early Genes
Research

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Synergistic activation of NF-κB by bacterial chemoattractant and TNFα is mediated by p38 MAPK-dependent RelA acetylation. / Pan, Warren W.; Li, Jain Dong; Huang, Shuang; Papadimos, Thomas J.; Pan, Zhixing K.; Chen, Ling Yu.

In: Journal of Biological Chemistry, Vol. 285, No. 45, 05.11.2010, p. 34348-34354.

Research output: Contribution to journalArticle

Pan, Warren W. ; Li, Jain Dong ; Huang, Shuang ; Papadimos, Thomas J. ; Pan, Zhixing K. ; Chen, Ling Yu. / Synergistic activation of NF-κB by bacterial chemoattractant and TNFα is mediated by p38 MAPK-dependent RelA acetylation. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 45. pp. 34348-34354.
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