TLR-Activated Gap Junction Channels Protect Mice against Bacterial Infection through Extracellular UDP Release

The Journal of Immunology : Official Journal of the American Association of Immunologists
Juliang QinBing Du

Abstract

Extracellular UDP (eUDP), released as a danger signal by stressed or apoptotic cells, plays an important role in a series of physiological processes. Although the mechanism of eUDP release in apoptotic cells has been well defined, how the eUDP is released in innate immune responses remains unknown. In this study, we demonstrated that UDP was released in both Escherichia coli-infected mice and LPS- or Pam3CSK4-treated macrophages. Also, LPS-induced UDP release could be significantly blocked by selective TLR4 inhibitor Atractylenolide I and selective gap junction inhibitors carbenoxolone and flufenamic acid (FFA), suggesting the key role of TLR signaling and gap junction channels in this process. Meanwhile, eUDP protected mice from peritonitis by reducing invaded bacteria that could be rescued by MRS2578 (selective P2Y6 receptor inhibitor) and FFA. Then, connexin 43, as one of the gap junction proteins, was found to be clearly increased by LPS in a dose- and time-dependent manner. Furthermore, if we blocked LPS-induced ERK signaling by U0126, the expression of connexin 43 and UDP release was also inhibited dramatically. In addition, UDP-induced MCP-1 secretion was significantly reduced by MRS2578, FFA, and P2Y6 mutation. Accordin...Continue Reading

References

Mar 24, 1977·Cell and Tissue Research·Y Shibata, T Yamamoto
Mar 24, 1995·Science·A G ReaumeJ Rossant
Jan 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eliseo A EugenínJuan C Sáez
Oct 25, 2003·Journal of Cell Science·Bruce J Nicholson
Feb 25, 2006·Cell·Shizuo AkiraOsamu Takeuchi
Apr 6, 2007·Nature·Schuichi KoizumiKazuhide Inoue
May 1, 2007·Progress in Biophysics and Molecular Biology·Joost NeijssenJacques Neefjes
Apr 29, 2008·Nature Immunology·Tatsukata KawagoeShizuo Akira
Aug 5, 2008·Journal of Immunological Methods·Attiya Alatery, Sameh Basta
Feb 15, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Beomsue KimEun-hye Joe
Mar 30, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhi ZhangMin Qian
Jun 6, 2013·Mediators of Inflammation·Pablo J SáezJuan C Sáez
Aug 21, 2013·Molecular Immunology·Zaridatul Aini IbrahimMaria B Sukkar
Jan 28, 2014·Nature·Kristin WestphalenJahar Bhattacharya
May 16, 2014·Nature·Marco IdzkoHolger K Eltzschig
Sep 28, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ruimei LiBing Du
Feb 3, 2015·Ageing Research Reviews·Noa FeldmanEitan Okun
Jun 10, 2015·Proceedings of the National Academy of Sciences of the United States of America·Francesca GrazianoGuido Poli

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Citations

Jul 9, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chengfei ZhangBing Du
Oct 21, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chen ShenJi Hyun Park
Sep 22, 2017·Pharmacological Reviews·Luc LeybaertRainer Schulz
Apr 20, 2018·International Journal of Molecular Sciences·Michel DoschGuido Beldi
Dec 2, 2017·International Reviews of Immunology·Komal DolasiaSangita Mukhopadhyay
Nov 22, 2016·Cellular & Molecular Immunology·Xiaoyu ZhangBing Du
Sep 19, 2017·Frontiers in Immunology·María Alejandra GleisnerAndrés Tittarelli
Feb 13, 2021·International Journal of Molecular Sciences·Daniel RodjakovicGuido Beldi
Mar 14, 2021·Apoptosis : an International Journal on Programmed Cell Death·Atsushi MuraoPing Wang
Apr 17, 2021·Biochemical and Biophysical Research Communications·Ling ZhuLi-Qun Yang
May 7, 2021·Frontiers in Pharmacology·Hongxing WangXiaotian Chang
Jun 29, 2021·Frontiers in Immunology·Tom O J CockramGuy C Brown
Jul 17, 2021·Archives of Pharmacal Research·Mao DengXiaofang Li
Aug 28, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Andrés Tittarelli

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