p204 Is Required for Canonical Lipopolysaccharide-induced TLR4 Signaling in Mice

EBioMedicine
Young-Su YiChuanju Liu

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.

References

Feb 28, 2002·Annual Review of Immunology·Charles A Janeway, Ruslan Medzhitov
Mar 22, 2002·Nature Reviews. Immunology·R Medzhitov
Apr 10, 2002·Molecular and Cellular Biology·Chuan-ju LiuPeter Lengyel
Jan 7, 2003·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Marco De AndreaSanto Landolfo
Jun 7, 2003·Science·Gregory M Barton, Ruslan Medzhitov
Aug 11, 2004·The Journal of Experimental Medicine·Victoria AuerbuchDaniel A Portnoy
Sep 30, 2004·Nature Immunology·Akiko Iwasaki, Ruslan Medzhitov
Aug 2, 2006·The Journal of Experimental Medicine·Daniel B Stetson, Ruslan Medzhitov
Sep 19, 2006·Immunity·Daniel B Stetson, Ruslan Medzhitov
Jan 1, 2008·The Journal of Biological Chemistry·Bo Ding, Peter Lengyel
Jan 23, 2009·Nature·Teresa Fernandes-AlnemriEmad S Alnemri
Jan 23, 2009·Nature Immunology·Tilmann BürckstümmerGiulio Superti-Furga
Nov 19, 2009·Cellular and Molecular Life Sciences : CMLS·Peter Lengyel, C J Liu
Mar 23, 2010·Cell·Osamu Takeuchi, Shizuo Akira
Oct 5, 2010·Nature Immunology·Leonie UnterholznerAndrew G Bowie
Feb 26, 2011·Immunological Reviews·Annette PlüddemannSiamon Gordon
Oct 18, 2011·Nature·Nobuhiko KayagakiVishva M Dixit
Mar 21, 2012·Current Opinion in Structural Biology·Ryan Ferrao, Hao Wu
Feb 8, 2013·Proceedings of the National Academy of Sciences of the United States of America·Takeshi KondoTaro Kawai
Jul 28, 2013·Science·Nobuhiko KayagakiVishva M Dixit
Oct 25, 2013·Proceedings of the National Academy of Sciences of the United States of America·Martin R JakobsenSøren R Paludan
Dec 18, 2013·Science·Ophir ShalemFeng Zhang
Mar 25, 2014·Annual Review of Immunology·Jiaxi Wu, Zhijian J Chen
Apr 29, 2014·Molecular Cell·Xin CaiZhijian J Chen
Jul 26, 2014·Nature Reviews. Immunology·Nicholas J GayClare E Bryant
Aug 15, 2014·Nature·Delphine GoubauCaetano Reis e Sousa

❮ Previous
Next ❯

Citations

Jun 18, 2019·Acta Crystallographica. Section F, Structural Biology Communications·Yuan Tian, Qian Yin
Apr 25, 2018·Scientific Reports·Jinlong JianYongxiang Shi
Feb 24, 2021·Nucleic Acids Research·Xiaojiao FanTengchuan Jin

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
Transfection
enzyme-linked immunosorbent assay
ELISAs
electrophoresis
immunoprecipitation
Assay
pull-down
nuclear translocation
co-immunoprecipitation assay

Software Mentioned

Statistical Package for the Social Sciences

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.