ER Stress Sensitizes TLR Signaling and Desensitizes LPS Tolerance Through IRE1a-mediated Activation of GSK-3b?

Event Abstract Back to Event ER Stress Sensitizes TLR Signaling and Desensitizes LPS Tolerance through IRE1a-mediated Activation of GSK-3b Sena Kim1, Yeonsoo Joe1, Jaekyoon Shin2, Stefan W. Ryter3 and Hun Taeg Chung1* 1 University of Ulsan, Republic of Korea 2 School of Medicine and Samsung Biomedical Research Institute, Sungkyunkwan University, Republic of Korea 3 Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, United States Tolerance to endotoxin that is triggered by prior exposure to toll-like receptor (TLR) lignads, provides a mechanism with which to dampen inflammatory cytokines. The ER stress activates GSK-3b to regulate the expression of inflammatory cytokines. Here we found that ER stress induces stimulation of IRE1a-mediated tyrosine phosphorylation and serine dephosphorylation of GSK-3b, which synergistically activates TLR signaling for cytokine production and obliterates endotoxin tolerance. Furthermore, activated GSK-3b increases the abundance of nuclear coactivator, RIP140 which enhances proinflammatory cytokine production and decreases anti-inflammatory cytokine production. Our results identify an unsuspected critical role for IRE1a-mediated GSK-3b activation in inflammation and endotoxin tolerance. Acknowledgements This study was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MEST) (2012M3A9C3048687). Keywords: Toll-Like Receptor 4, Endotoxin tolerance, GSK-3, er stress, Inflammation Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: Kim S, Joe Y, Shin J, Ryter SW and Chung H (2013). ER Stress Sensitizes TLR Signaling and Desensitizes LPS Tolerance through IRE1a-mediated Activation of GSK-3b. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01143 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 25 Jul 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Hun Taeg Chung, University of Ulsan, Ulsan, Republic of Korea, chung@ulsan.ac.kr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Sena Kim Yeonsoo Joe Jaekyoon Shin Stefan W Ryter Hun Taeg Chung Google Sena Kim Yeonsoo Joe Jaekyoon Shin Stefan W Ryter Hun Taeg Chung Google Scholar Sena Kim Yeonsoo Joe Jaekyoon Shin Stefan W Ryter Hun Taeg Chung PubMed Sena Kim Yeonsoo Joe Jaekyoon Shin Stefan W Ryter Hun Taeg Chung Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.