p38 activation through Toll-like receptors modulates IFN-γ-induced expression of the Tap-1 gene only in macrophages

Alicia A. Cecil, Michael Klemsz

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Although interferon-γ (IFN-γ) induces the transporter associated with antigen processing (Tap)-1 expression in macrophages, cooperation with lipopolysaccharide signaling through Toll-like receptor 4 (TLR4) accelerates the kinetics and increases the overall levels of this gene. In this report, we show that peptidoglycan signaling through TLR2 and bacterial CpG DNA signaling through TLR9 are functionally equivalent at synergizing with IFN-γ in regulating Tap-1 expression in macrophages. Activation of the p38 mitogen-activated protein kinase is necessary for this response, which correlates with increased phosphorylation of signal transducer and activator of transcription-1 on serine 727. Activation of p38, however, is not sufficient, as this signaling event does not affect the response to IFN-γ in HeLa cells. The cooperation between these different signaling pathways also requires membrane fluidity. These data suggest that macrophages possess an ability to coordinate the signaling between the IFN-γ and TLR receptors.

Original languageEnglish
Pages (from-to)560-568
Number of pages9
JournalJournal of Leukocyte Biology
Volume75
Issue number3
DOIs
StatePublished - Mar 2004

Fingerprint

Toll-Like Receptors
Interferons
Macrophages
Interferon Receptors
STAT1 Transcription Factor
Genes
Bacterial DNA
Toll-Like Receptor 4
Membrane Fluidity
Peptidoglycan
Antigen Presentation
p38 Mitogen-Activated Protein Kinases
HeLa Cells
Serine
Lipopolysaccharides
Phosphorylation

Keywords

  • Gene regulation
  • Macrophages
  • Transcription factor

ASJC Scopus subject areas

  • Cell Biology

Cite this

p38 activation through Toll-like receptors modulates IFN-γ-induced expression of the Tap-1 gene only in macrophages. / Cecil, Alicia A.; Klemsz, Michael.

In: Journal of Leukocyte Biology, Vol. 75, No. 3, 03.2004, p. 560-568.

Research output: Contribution to journalArticle

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