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DOI | 10.1126/science.aau6499 |
IRE1 alpha-XBP1 signaling in leukocytes controls prostaglandin biosynthesis and pain | |
Chopra, Sahil1,2,3,18; Giovanelli, Paolo1,2,3; Alvarado-Vazquez, Perla Abigail4; Alonso, Sara5; Song, Minkyung2,3; Sandoval, Tito A.2,3; Chae, Chang-Suk2,3; Tan, Chen2,3; Fonseca, Miriam M.4; Gutierrez, Silvia4; Jimenez, Leandro6,7; Subbaramaiah, Kotha8; Iwawaki, Takao9; Kingsley, Philip J.10; Marnett, Lawrence J.10,11,12,13; Kossenkov, Andrew V.14; Crespo, Mariano Sanchez5; Dannenberg, Andrew J.8; Glimcher, Laurie H.15,16,17; Romero-Sandoval, E. Alfonso4; Cubillos-Ruiz, Juan R.1,2,3 | |
2019-07-19 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 365期号:6450页码:248-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Spain; Brazil; Japan |
英文摘要 | Inositol-requiring enzyme 1[alpha] (IRE1[alpha])-X-box binding protein spliced (XBP1) signaling maintains endoplasmic reticulum (ER) homeostasis while controlling immunometabolic processes. Yet, the physiological consequences of IRE1 alpha-XBP1 activation in leukocytes remain unexplored. We found that induction of prostaglandin-endoperoxide synthase 2 (Ptgs2/Cox-2) and prostaglandin E synthase (Ptges/mPGES-1) was compromised in IRE1 alpha-deficient myeloid cells undergoing ER stress or stimulated through pattern recognition receptors. Inducible biosynthesis of prostaglandins, including the pro-algesic mediator prostaglandin E2 (PGE(2)), was decreased in myeloid cells that lack IRE1 alpha or XBP1 but not other ER stress sensors. Functional XBP1 transactivated the human PTGS2 and PTGES genes to enable optimal PGE(2) production. Mice that lack IRE1 alpha-XBP1 in leukocytes, or that were treated with IRE1 alpha inhibitors, demonstrated reduced pain behaviors in PGE(2)-dependent models of pain. Thus. IRE1 alpha-XBP1 is a mediator of prostaglandin biosynthesis and a potential target to control pain. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000476479200043 |
WOS关键词 | ENDOPLASMIC-RETICULUM STRESS ; UNFOLDED-PROTEIN-RESPONSE ; RAT MODEL ; ER STRESS ; AMNIOTIC-FLUID ; MESSENGER-RNA ; UP-REGULATION ; MICE LACKING ; IRE1 ; EXPRESSION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/201896 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Cornell Univ, Weill Cornell Grad Sch Med Sci, New York, NY 10065 USA; 2.Weill Cornell Med, Dept Obstet & Gynecol, New York, NY 10065 USA; 3.Weill Cornell Med, Sandra & Edward Meyer Canc Ctr, New York, NY 10065 USA; 4.Wake Forest Univ, Bowman Gray Sch Med, Pain Mech Lab, Dept Anesthesiol, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA; 5.Univ Valladolid, CSIC, Inst Biol & Genet Mol, Valladolid, Spain; 6.Inst Ludwig Pesquisa Canc, Sao Paulo, Brazil; 7.Hosp Sirio Libanes, Sao Paulo, Brazil; 8.Weill Cornell Med, Dept Med, New York, NY 10065 USA; 9.Kanazawa Med Univ, Med Res Inst, Div Cell Med, Uchinada, Ishikawa, Japan; 10.Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA; 11.Vanderbilt Univ, Vanderbilt Inst Chem Biol, AB Hancock Jr Mem Lab Canc Res, Dept Biochem, Nashville, TN 37232 USA; 12.Vanderbilt Univ, Vanderbilt Inst Chem Biol, AB Hancock Jr Mem Lab Canc Res, Dept Chem, Nashville, TN 37232 USA; 13.Vanderbilt Univ, Vanderbilt Inst Chem Biol, AB Hancock Jr Mem Lab Canc Res, Dept Pharmacol, Nashville, TN 37232 USA; 14.Wistar Inst Anat & Biol, Ctr Syst & Computat Biol, 3601 Spruce St, Philadelphia, PA 19104 USA; 15.Harvard Med Sch, Dept Med, Boston, MA 02115 USA; 16.Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA; 17.Harvard Med Sch, Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02215 USA; 18.Vertex Ventures HC, 345 Calif Ave, Palo Alto, CA 94306 USA |
推荐引用方式 GB/T 7714 | Chopra, Sahil,Giovanelli, Paolo,Alvarado-Vazquez, Perla Abigail,et al. IRE1 alpha-XBP1 signaling in leukocytes controls prostaglandin biosynthesis and pain[J]. SCIENCE,2019,365(6450):248-+. |
APA | Chopra, Sahil.,Giovanelli, Paolo.,Alvarado-Vazquez, Perla Abigail.,Alonso, Sara.,Song, Minkyung.,...&Cubillos-Ruiz, Juan R..(2019).IRE1 alpha-XBP1 signaling in leukocytes controls prostaglandin biosynthesis and pain.SCIENCE,365(6450),248-+. |
MLA | Chopra, Sahil,et al."IRE1 alpha-XBP1 signaling in leukocytes controls prostaglandin biosynthesis and pain".SCIENCE 365.6450(2019):248-+. |
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