ADP/P2Y1 aggravates inflammatory bowel disease through ERK5-mediated NLRP3 inflammasome activation.

Mucosal Immunology
Chengfei ZhangBing Du

Abstract

Inflammasomes are essential for inflammation and pathogen elimination in response to microbial infection and endogenous danger signals. However, the mechanism of inflammasome activation by endogenous danger signals mediated posttranslational modification and the connection between inflammasomes and inflammatory diseases remains elusive. In this study, we found that ADP was highly released from injured colonic tissue as a danger signal during inflammatory bowel disease. Consequently, extracellular ADP activated the NLRP3 inflammasome through P2Y1 receptor-mediated calcium signaling, which led to the maturation and secretion of IL-1β and further aggravation of experimental colitis. Genetic ablation or pharmacological blockade of the P2Y1 receptor significantly ameliorated DSS-induced colitis and endotoxic shock through reducing NLRP3 inflammasome activation. Moreover, ERK5-mediated tyrosine phosphorylation of ASC was essential for activation of the NLRP3 inflammasome. Thus, our study provides a novel theoretical basis for posttranslational modification of ASC in NLRP3 inflammasome activation and revealed that ADP/P2Y1 is a potential drug target for inflammatory bowel disease.

References

May 26, 1995·The Journal of Biological Chemistry·G ZhouJ E Dixon
Aug 5, 2003·The Journal of Clinical Investigation·Patrick AndrePamela B Conley
Oct 6, 2006·Nucleic Acids Research·Paola SacchettiPhilippe Lefebvre
Dec 26, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rachael NatrajanChris Jones
Mar 5, 2010·European Journal of Immunology·Sébastien A LévesqueJean Sévigny
Jun 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Tomohiko MurakamiTiffany Horng
Sep 6, 2012·Nature Communications·Yosuke KurashimaHiroshi Kiyono
Dec 14, 2012·The New England Journal of Medicine·Holger K EltzschigSimon C Robson
May 25, 2013·Nature Reviews. Immunology·Eicke LatzAndrea Stutz
Apr 23, 2014·Nature Reviews. Immunology·Markus F Neurath
Jun 18, 2014·The Journal of Clinical Investigation·Joonseok ChoByeong Chel Lee
Sep 28, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ruimei LiBing Du
Feb 3, 2015·Trends in Cell Biology·Sivapriya K VanajaKatherine A Fitzgerald
Mar 31, 2015·Nature·Dandan ZhangBeili Wu
Apr 4, 2015·Molecular Pharmacology·Kenneth A JacobsonEvgeny Kiselev
Apr 17, 2015·Immunological Reviews·Ine Jorgensen, Edward A Miao
Jun 30, 2015·Nature Medicine·Haitao GuoJenny P-Y Ting
Oct 4, 2015·Trends in Immunology·Matthew V Russo, Dorian B McGavern
Nov 22, 2016·Cellular & Molecular Immunology·Xiaoyu ZhangBing Du
Dec 5, 2016·Lancet·Ryan UngaroJean-Frédéric Colombel
Jul 9, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chengfei ZhangBing Du
Nov 10, 2017·International Journal of Molecular Sciences·Nicole RansonRajaraman Eri
Dec 22, 2017·Nature Communications·Nathan H KipnissLei S Qi
Jul 29, 2018·Trends in Pharmacological Sciences·Tiantian TangRongbin Zhou
Aug 24, 2018·Journal of Molecular Cell Biology·Chengfei ZhangBing Du

❮ Previous
Next ❯

Citations

Apr 15, 2021·Cellular & Molecular Immunology·Seungwha PaikEun-Kyeong Jo

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
transfection
immunoprecipitation
Assay
lavage
PCR

Software Mentioned

GraphPad Prism

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.

Related Papers

The New England Journal of Medicine
Thirumala-Devi Kanneganti
World Journal of Gastroenterology : WJG
Evanthia TourkochristouChristos Triantos
© 2022 Meta ULC. All rights reserved