The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
STAT1 plays a role in TLR signal transduction and inflammatory responses
Abstract
Activation of the Toll-like receptor (TLR) family of innate immune sensors stimulates multiple signal transduction pathways. Previous studies have suggested that TLR2, TLR4 and TLR9 induce serine phosphorylation of Signal Transducers and Activators of Transcription-1 (STAT1) at residue 727 (S727), although its role in TLR signaling was unclear. We report here that STAT1 rapidly undergoes phosphorylation following TLR4 challenge with lipopolysaccharide (LPS) in a model of LPS hypersensitivity in vivo. Importantly, genetic ablation of STAT1 protected against LPS-induced lethality suggesting that STAT1 may have a key role in TLR-induced inflammation. We have found that multiple TLRs induce Ser727 phosphorylation of STAT1, which is dependent on MyD88 and TRIF signaling, but independent of interferon (IFN) regulatory factor (IRF)-3, IRF7 and the IFN receptor complex, suggesting that activation is a direct TLR response rather than autocrine activation via IFN. Importantly, we found that STAT1 interacts with tumor necrosis factor (TNF) receptor-associated factor-6 (TRAF6), a key mediator of TLR signaling after TLR challenge and that following activation, STAT1 translocates to the nucleus. Critically, macrophages generated from mice in which the S727 residue was replaced with alanine (STAT1 S727A mice) display significantly reduced TNFα protein production, but not reduced interleukin-6 or RANTES protein in response to multiple TLR challenges, as compared with wild-type macrophages. T…
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“There is growing acknowledgement of the role that the Type I IFN response plays over the TLRinduced classical inflammatory response (Luu et al., 2014)(Taylor et al., 2014).”
From TET2 Regulates the Neuroinflammatory Response in Microglia (2019) · cites this paper as Luu et al., 2014
In the citing paper
“We found that TET2 regulates primarily genes involved in the innate immune response and more specifically genes related to the TLR induced-Type I IFN response (e.g., Stat1, Stat3, Irf1, Irf7 ) (Noppert et al., 2007)(Luu et al., 2014).”
From TET2 Regulates the Neuroinflammatory Response in Microglia (2019) · cites this paper as Luu et al., 2014
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LPS-TLR4 Signaling to IRF-3/7 and NF-κB Involves the Toll Adapters TRAM and TRIF
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Walsh, M. C., Lee, J., & Choi, Y. (2015) · Immunological Reviews · doi:10.1111/imr.12302 · Cited by 451
Menon, M., Blair, P. A., Isenberg, D. A., & Mauri, C. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.012 · Cited by 374
Malyshev, I. Y., & Malyshev, Y. (2015) · BioMed Research International · doi:10.1155/2015/341308 · Cited by 293
Roy, A., Srivastava, M., Saqib, U., Liu, D., Faisal, S. M., Sugathan, S., Bishnoi, S., & Baig, M. S. (2016) · International Immunopharmacology · doi:10.1016/j.intimp.2016.08.026 · Cited by 196
Xu, S., Wang, J., Jiang, J., Song, J., Zhu, W. P., Zhang, F., Shao, M., Xu, H., Ma, X., & Lyu, F. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-02824-z · Cited by 171
Metadata
- Authors
- Luu, K., Greenhill, C. J., Majoros, A., Decker, T., Jenkins, B. J., & Mansell, A.
- Affiliations
- Hudson Institute of Medical Research (AU)
- University of Vienna (AT)
- Corresponding author
- Jenkins, Brendan J
- Mansell, Ashley
- Venue
- Immunology & Cell Biology
- Publisher
- Wiley
- Published
- 2014-07-15
- Volume
- 92
- Issue
- 9
- Pages
- 761-769
- ISSN
- 0004-945X (ISSN-L)
- 0818-9641
- 1440-1711
- OpenAlex
- W1991465901
- Cited by
- 151
- References
- 32
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 20 · 2023: 4 · 2022: 10 · 2021: 11 · 2020: 15 · 2019: 14 · 2018: 12 · 2017: 15 · 2016: 11 · 2015: 13 · 2014: 1
- FWCI
- 6.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Immunology and Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council of Australia
- Operational Infrastructure Support Program of the Victorian Government of Australia
- Senior Medical Research Fellowship
- Sylvia and Charles Viertel Foundation
- NHMRC Research Fellowship
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- STAT1, Toll-like receptors, TLR4, lipopolysaccharide, serine phosphorylation, MyD88, TRIF, TRAF6, JAK/STAT signaling, innate immunity, inflammation, macrophages, TNF-α, STAT1 nuclear translocation
- MeSH terms
- Animals, Cells, Cultured, Inflammation, Lipopolysaccharides, Macrophages, Phosphorylation, Tumor Necrosis Factor-alpha, Signal Transduction, Interleukin-6, Chemokine CCL5, Adaptor Proteins, Vesicular Transport, TNF Receptor-Associated Factor 6, STAT1 Transcription Factor, Interferon Regulatory Factor-3, Interferon Regulatory Factor-7, Toll-Like Receptors, Mice, Myeloid Differentiation Factor 88, Janus Kinases
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