IRE1α–XBP1 signaling in leukocytes controls prostaglandin biosynthesis and pain
Abstract
The unfolded protein response (UPR) is initiated when unfolded or misfolded proteins accumulate in the endoplasmic reticulum. One highly conserved arm of the UPR, the IRE1α–XBP1 signaling pathway, also plays a role in various other UPR-independent processes, including hypoxia, angiogenesis, and inflammation. Chopra et al. report that this pathway additionally regulates the production of two molecules, cyclooxygenase 2 and microsomal prostaglandin E synthase 1, that help mediate inflammation-induced pain (see the Perspective by Avril and Chevet). When elements of the IRE1α–XBP1 signaling pathway were knocked out, pain behaviors were reduced in two different mouse models of pain. Targeting this pathway may result in improved pain management therapies.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 19, 2019
- Source ID
- 10.1126/science.aau6499
Entities
People
- Andrew J. Dannenberg
- Andrew V Kossenkov
- Chang-Suk Chae
- Chen Tan
- E Alfonso Romero-Sandoval
- Juan R Cubillos-Ruiz
- Kotha Subbaramaiah
- Laurie H. Glimcher
- Lawrence J. Marnett
- Leandro Jimenez
- Mariano Sánchez Crespo
- Minkyung Song
- Miriam M Fonseca
- Paolo Giovanelli
- Perla Abigail Alvarado-Vazquez
- Philip J. Kingsley
- Sahil Chopra
- Sara Alonso
- Silvia Gutierrez
- Takao Iwawaki
- Tito A Sandoval
Organizations
- Cornell University
- Harvard Medical School
- Hospital Sírio-Libanês
- National Institutes of Health
- United States Department of Defense
- Vanderbilt University
- Wake Forest University
- Weill Cornell Medicine
- Wistar Institute