Abstract
In Cystic Fibrosis (CF), the absence of functional Cystic Fibrosis Transmembrane conductance Regulator (CFTR) translates into chronic bacterial infection, excessive inflammation, tissue damage, impaired lung function and eventual death. Understanding the mechanisms underlying this vicious circle of inflammation is key to better therapies for CF. In this manuscript, we have found that the presence of IL-17 in the airways of CF patients not only exacerbates inflammation through the recruitment of neutrophils via secretion of CXCL8, but also by priming airway epithelial cells lacking functional CFTR to increase response to the bacterial sensor NOD1. IL-17 stimulation of airway epithelial cells (AECs) lacking functional CFTR increased the expression of NOD1, NOD2, TLR4 and its own receptors IL-17RA and IL-17RC. Moreover, prior stimulation of AECs expressing the CFTRDeltaF508 mutant with IL-17 showed much greater CXCL8 secretion in response to a NOD1 agonist and Pseudomonas aeruginosa diffusible material. Taken together our results show that IL-17 primes AECs expressing CFTRDeltaF508 to increase host defence response to bacteria through the up-regulation of PRRs, and in particular of NOD1, and identifies another mechanism of action ...Continue Reading
References
Dec 1, 1989·The American Review of Respiratory Disease·R S BaltimoreG J Smith
Feb 13, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·D KubeP B Davis
Mar 30, 2001·The Journal of Biological Chemistry·A J RatnerA Prince
May 9, 2001·Nucleic Acids Research·M W Pfaffl
Jun 14, 2001·Inflammation·A A StecenkoK L Brigham
Apr 5, 2002·Clinical Microbiology Reviews·Jeffrey B LyczakGerald B Pier
May 16, 2002·Chest·Jadwiga A Wedzicha
Jun 6, 2003·The Journal of Allergy and Clinical Immunology·Jamila ChakirQutayba Hamid
Oct 16, 2004·Immunity·Jay K Kolls, Anders Lindén
Apr 5, 2005·Respiratory Research·Qi WuScott H Randell
Jun 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Florencia McAllisterJay K Kolls
Dec 14, 2005·Current Opinion in Immunology·Luke A J O'Neill
Sep 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Muhammad Shahidur RahmanAbdelilah Soussi Gounni
Nov 18, 2006·Nature Immunology·Jörg H FritzStephen E Girardin
Nov 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Spencer C LiangLynette A Fouser
Oct 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chuanwang SongZuo-Hua Feng
Jan 6, 2009·Cellular Signalling·Julie BérubéSimon Rousseau
Oct 15, 2009·Science Signaling·Caini LiuXiaoxia Li
Citations
Aug 30, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Haouaria BalghiJohn W Hanrahan
Apr 9, 2011·American Journal of Respiratory and Critical Care Medicine·Hui-Leng TanJane C Davies
Jan 12, 2013·American Journal of Respiratory and Critical Care Medicine·Rossana G IannittiLuigina Romani
Apr 16, 2011·American Journal of Respiratory Cell and Molecular Biology·Stephanie RobinsSimon Rousseau
May 29, 2010·BMC Genomics·Stephen MutolokiØystein Evensen
Apr 3, 2012·Journal of Pharmacological Sciences·Shota MizunoeHirofumi Kai
Jun 16, 2017·Physiological Reviews·Paul J BakerSeth L Masters
Oct 13, 2015·Science Advances·Shantelle L LaFayetteDao Nguyen
Sep 4, 2015·Pediatric Pulmonology·David P Nichols, James F Chmiel
Nov 13, 2019·Pediatric Pulmonology·Lucy Perrem, Felix Ratjen
Jun 1, 2018·Mediators of Inflammation·Virginia De RoseCatherine M Greene
Sep 2, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Stephen J Gurczynski, Bethany B Moore
Apr 2, 2021·Stem Cell Research & Therapy·Yan LiDahai Hu
Oct 1, 2010·Current Opinion in Pulmonary Medicine