Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/33316
Title: Leukotriene E4 is a full functional agonist for human cysteinyl leukotriene type 1 receptor
Authors: Foster, H. R.
Fuerst, E.
Branchett, W.
Lee, T. H.
Cousins, David J.
Woszczek, G.
First Published: 2015
Publisher: Rockefeller University Press
Citation: Journal of Experimental Medicine
Abstract: Leukotriene E4 (LTE4) the most stable of the cysteinyl leukotrienes (cysLTs) binds poorly to classical type 1 (CysLT1) and 2 (CysLT2) receptors although it induces potent responses in human airways in vivo, such as bronchoconstriction, airway hyperresponsiveness and inflammatory cell influx suggesting the presence of a novel receptor that preferentially responds to LTE4. To identify such a receptor two human mast cell lines, LAD2 and LUVA, were selected that differentially responded to LTE4 when analyzed by intracellular signaling and gene expression. Comparative transcriptome analysis and recombinant gene overexpression experiments revealed CysLT1 as a receptor responsible for potent LTE4-induced response in LAD2 but not in LUVA cells, an observation confirmed further by gene knockdown and selective inhibitors. Lentiviral overexpression of CysLT1 in LUVA cells augmented intracellular calcium signaling induced by LTE4 but did not restore full agonist responses at the gene expression level. Our data support a model where both an increased expression of Gαq-coupled CysLT1, and sustained intracellular calcium mobilization and extracellular signal-regulated kinase (Erk) activation, are required for LTE4-mediated regulation of gene expression in human cells. Our study shows for the first time that CysLT1 expression is critically important for responsiveness to LTE4 within a human cell system.
DOI Link: TBA
ISSN: 1540-9538
eISSN: 1540-9538
Links: TBA
http://hdl.handle.net/2381/33316
Embargo on file until: 1-Jan-10000
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: For the first six months after publication, RUP grants the public the non-exclusive right to copy, distribute, or display the Work, under the following conditions: Attribution, Noncommercial, Share Alike, No Mirror Sites. Beginning six months after publication, RUP grants the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode.
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

Files in This Item:
File Description SizeFormat 
43988_0_merged_1439907297.pdfPre-review (submitted draft)1.7 MBAdobe PDFView/Open


Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.