Cell type- and developmental stage-specific activation of NF-κB by fMet-Leu-Phe in myeloid cells

Darren D. Browning, Zhixing K. Pan, Eric R. Prossnitz, Richard D. Ye

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Chemoattractants induce a variety of phagocytic functions including transendothelial migration, degranulation, and the generation of superoxide anions. We report here that the prototypic chemotactic peptide fMet-Leu-Phe (fMLF) stimulates the activation of nuclear factor-κB (NF-κB), a transcription factor that is central to the regulation of proinflammatory immediate-early gene expression. In freshly prepared peripheral blood mononuclear cells, fMLF (1-100 nM) induced a κB binding activity that was receptor-dependent and involved the p50 and p65 subunits of the NF-κB/Rel family of proteins. The activation of NF-κB by fMLF appeared to be cell- specific and different from the activation of NF-κB by tumor necrosis factor-α (TNFα). Neutrophil preparations that responded to fMLF, TNFα, and lipopolysaccharides with interleukin-8 secretion did not show NF-κB activation, whereas N-formyl peptide receptor (FPR)-transfected HL-60 cells were responsive to TNFα but not fMLF for NF-κB activation. Differentiation of FPR-transfected HL-60 cells with dimethyl sulfoxide for 3-5 days conferred the capability of the cells to activate NF-κB in response to fMLF without a significant increase in the amount of FPR. These results identify NF-κB as a transcription factor that can be activated by the prototypic chemotactic peptide and demonstrate that this function is both highly regulated and dependent on signaling components specifically expressed during myeloid differentiation.

Original languageEnglish (US)
Pages (from-to)7995-8001
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number12
DOIs
StatePublished - 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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