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p38 activation through Toll‐like receptors modulates IFN‐γ‐induced expression of the Tap‐1 gene only in macrophages
Author(s) -
Cecil Alicia A.,
Klemsz Michael J.
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0803375
Subject(s) - biology , receptor , microbiology and biotechnology , toll like receptor , p38 mitogen activated protein kinases , gene expression , gene , toll , signal transduction , innate immune system , immunology , genetics , mapk/erk pathway
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.