We previously reported that Toll-like receptor-2 (TLR2) agonists induce expression of a more limited repertoire of pro-inflammatory genes than TLR4 agonists. Murine macrophages stimulated with the TLR4 agonist, Escherichia coli lipopolysaccharide, induced signal transducer and activator of transcription 1 (‘STAT1’) tyrosine phosphorylation that was secondary to the autocrine/paracrine action of interferon (IFN)-β, an immediate early gene. In contrast, TLR2 agonists failed to activate IFN-β gene expression. TLR4-induced IFN-β mRNA was found to be MyD88- and PKR (double-stranded RNA-dependent protein kinase)-independent, but TIRAP (Toll/interleukin-1 receptor domain-containing adapter protein)/Mal (MyD88-adapter-like)-dependent. In the present paper, we outline the recent controversy over the role of TIRAP/Mal in TLR2 and TLR4 signalling in the context of the current molecular tools used for such studies. Collectively, our findings provide the first mechanistic basis for differential patterns of gene expression activated by TLR4 and TLR2 agonists.
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Conference Article|
June 01 2003
Toll-like receptor 4 signalling: new perspectives on a complex signal-transduction problem
S.N. Vogel;
S.N. Vogel
1
Department of Microbiology and Immunology, and Department of Medicine, University of Maryland, Baltimore, 655 W. Baltimore Street 13-009, Baltimore, MD 21201, U.S.A.
1To whom correspondence should be addressed (e-mail svogel@som.umaryland.edu).
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M. Fenton
M. Fenton
Department of Microbiology and Immunology, and Department of Medicine, University of Maryland, Baltimore, 655 W. Baltimore Street 13-009, Baltimore, MD 21201, U.S.A.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2003 Biochemical Society
2003
Biochem Soc Trans (2003) 31 (3): 664–668.
Citation
S.N. Vogel, M. Fenton; Toll-like receptor 4 signalling: new perspectives on a complex signal-transduction problem. Biochem Soc Trans 1 June 2003; 31 (3): 664–668. doi: https://doi.org/10.1042/bst0310664
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