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p204 Is Required for Canonical Lipopolysaccharide-induced TLR4 Signaling in Mice
- Source :
- EBioMedicine, Vol 29, Iss , Pp 78-91 (2018)
- Publication Year :
- 2018
- Publisher :
- Elsevier, 2018.
-
Abstract
- p204, a murine member of an interferon-inducible p200 family, was reported to recognize intracellular viral and bacterial DNAs, however, its role in the innate immunity in vivo remains unknown due to the lack of p204-deficient animal models. In this study we first generated the p204−/− mice. Unexpectedly, p204 deficiency led to significant defect in extracellular LPS signaling in macrophages, as demonstrated by dramatic reductions of LPS-mediated IFN-β and pro-inflammatory cytokines. The serum levels of IFN-β and pro-inflammatory cytokines were also significantly reduced in p204−/− mice following LPS challenge. In addition, p204−/− mice were resistant to LPS-induced shock. LPS-activated NF-ĸB and IRF-3 pathways were all defective in p204-deficient macrophages. p204 binds to TLR4 through its Pyrin domain, and it is required for the dimerization of TLR4 following LPS-challenge. Collectively, p204 is a critical component of canonical LPS-TLR4 signaling pathway, and these studies also suggest that p204 could be a potential target to prevent and treat inflammatory and infectious diseases. Keywords: p204, LPS, TLR4, IFN-β, Inflammatory responses, Macrophages
- Subjects :
- Medicine
Medicine (General)
R5-920
Subjects
Details
- Language :
- English
- ISSN :
- 23523964 and 30782171
- Volume :
- 29
- Issue :
- 78-91
- Database :
- Directory of Open Access Journals
- Journal :
- EBioMedicine
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.fa99e8c2b1ba46beb30782171d928f79
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.ebiom.2018.02.012