β-Arrestin-2-ERK1/2 cPLA2 α axis mediates TLR4 signaling to influence eicosanoid induction in ischemic brain

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Yanxiao XiangYuguo Chen

Abstract

LPS has been shown to elicit neuroinflammation associated with the up-regulation of the eicosanoid pathway in animal models; however, the regulatory mechanisms of TLR4 in brain neuroinflammatory conditions remain elusive. β-Arrestins are key regulators of the GPCR signaling pathway and are involved in the leukotriene B4-induced leukocyte migration to initiate inflammatory response. However, the roles of β-arrestins in eicosanoid regulation and related diseases are not clear. To address this issue, we conducted a study to investigate the effect of TLR4 on the eicosanoid pathway in ischemic stroke brain and to explore the underlying molecular regulation mechanism. Cerebral ischemia was produced by occlusion of the middle cerebral artery, followed by reperfusion for 24 h. We demonstrated that knockout of TLR4 improves ischemic stroke brain associated with eicosanoid down-regulation. Interestingly, genetic disruption of β-arrestin-2 failed to decrease neuroinflammation in the damaged brain of TLR4-/- mice, which indicates the requirement of β-arrestin-2 for TLR4 knockdown protection. Further study showed that the negative regulation of phosphorylated (phospho-)ERK1/2 and phospho-cytosolic phospholipase A2 α (cPLA2α) by TLR4 deficie...Continue Reading

References

Aug 1, 1986·Clinical and Experimental Pharmacology & Physiology·S C FaganF M Gengo
Jan 29, 1993·Cell·L L LinR J Davis
Dec 31, 2002·Brain Research·Koreaki Sugimoto, Costantino Iadecola
Jul 21, 2004·Neurobiology of Disease·Tatsurou YagamiGoro Katsuura
Jan 25, 2006·Nature Medicine·Takayuki KawanoCostantino Iadecola
Jun 17, 2006·Circulation Research·J MoccoE Sander Connolly
Feb 20, 2007·Annual Review of Physiology·Scott M DeWireSudha K Shenoy
Jan 9, 2008·Molecular Immunology·Katie LoniewskiNarayanan Parameswaran
Sep 26, 2008·The New England Journal of Medicine·Patrick Lyden
Nov 18, 2008·Proceedings of the National Academy of Sciences of the United States of America·Michael O BreckwoldtRalph Weissleder
Apr 30, 2009·Journal of Leukocyte Biology·Sabine C LindnerBernd L Sorg
Jan 6, 2011·Journal of Visualized Experiments : JoVE·Venkatakrishna R Jala, Bodduluri Haribabu
Apr 23, 2011·Lancet Neurology·Richard MacrezDenis Vivien
Mar 22, 2012·Medicinal Research Reviews·Valérie CapraG Enrico Rovati
May 3, 2012·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Andreas H JacobsUNKNOWN INMiND consortium
Jul 27, 2012·Frontiers in Immunology·Takashi ShichitaAkihiko Yoshimura
Dec 4, 2012·Nature Medicine·Amantha ThathiahBart De Strooper
Oct 12, 2013·Molecular Neurobiology·Tatsurou YagamiHiromi Koma
Jan 16, 2014·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Fan YangFan Yi
Dec 9, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Said Movahedi NainiJoseph V Bonventre
Jan 23, 2016·Journal of the American Heart Association·Natalia S RostUNKNOWN Global Comparators Stroke GOAL collaborators

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