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

Journal of Leukocyte Biology

Michael J. Klemsz¹  Alicia A. Cecil¹ 

[1]Department of Microbiology and Immunology, Indiana University School of Medicine and the Walther Cancer Institute, IndianapolisDepartment of Microbiology and Immunology, Indiana University School of Medicine and the Walther Cancer Institute, IndianapolisDepartment of Microbiology and Immunology, Indiana University School of Medicine and the Walther Cancer Institute, Indianapolis

关键词: gene regulation;    transcription factor;    macrophages;   

DOI  :  10.1189/jlb.0803375

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown