TLR4, but not TLR2, mediates IFN-beta-induced STAT1alpha/beta-dependent gene expression in macrophages

Autor: Vladimir, Toshchakov, Bryan W, Jones, Pin-Yu, Perera, Karen, Thomas, M Joshua, Cody, Shuling, Zhang, Bryan R G, Williams, Jennifer, Major, Thomas A, Hamilton, Matthew J, Fenton, Stefanie N, Vogel
Rok vydání: 2002
Předmět:
Lipopolysaccharides
Male
Gene Expression
Nitric Oxide Synthase Type II
Receptors
Cell Surface
Cell Line
Mice
Escherichia coli
Animals
Drosophila Proteins
RNA
Messenger
Phosphorylation
Receptors
Immunologic
Adaptor Proteins
Signal Transducing
Mice
Knockout
Mice
Inbred C3H
Membrane Glycoproteins
Tumor Necrosis Factor-alpha
Macrophages
Toll-Like Receptors
Receptors
Interleukin-1
Interferon-Stimulated Gene Factor 3
Interferon-beta
Antigens
Differentiation
Toll-Like Receptor 2
Monocyte Chemoattractant Proteins
Chemokine CXCL10
DNA-Binding Proteins
Enzyme Activation
Mice
Inbred C57BL
Toll-Like Receptor 4
STAT1 Transcription Factor
Myeloid Differentiation Factor 88
Trans-Activators
Female
Mitogen-Activated Protein Kinases
Nitric Oxide Synthase
Chemokines
CXC
Interleukin-1
Signal Transduction
Transcription Factors
Zdroj: Nature immunology. 3(4)
ISSN: 1529-2908
Popis: Toll-like receptor 2 (TLR2) agonists induce a subset of TLR4-inducible proinflammatory genes, which suggests the use of differential signaling pathways. Murine macrophages stimulated with the TLR4 agonist Escherichia coli lipopolysaccharide (LPS), but not with TLR2 agonists, induced phosphorylation of signal transducer and activator of transcription 1alpha (STAT1alpha) and STAT1beta, which was blocked by antibodies to interferon beta (IFN-beta) but not IFN-alpha. All TLR2 agonists poorly induced IFN-beta, which is encoded by an immediate early LPS-inducible gene. Thus, the failure of TLR2 agonists to induce STAT1-dependent genes resulted, in part, from their inability to express IFN-beta. TLR4-induced IFN-beta mRNA was MyD88- and PKR (double-stranded RNA-dependent protein kinase)-independent, but TIRAP (Toll-interleukin 1 receptor domain-containing adapter protein)-dependent. Together, these findings provide the first mechanistic basis for differential patterns of gene expression activated by TLR4 and TLR2 agonists.
Databáze: OpenAIRE
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