Inhibition of BET bromodomains restores corticosteroid responsiveness in a mixed granulocytic mouse model of asthma

Biochemical Pharmacology
A NadeemSabry M Attia

Abstract

Asthma is a heterogeneous disease characterized by different endotypes/phenotypes. Th2/Th17 driven mixed granulocytic asthma is one of them and shows resistance to corticosteroid therapy. Bromodomain and extra-terminal (BET) proteins are required for differentiation of Th17 cells which play a pivotal role in neutrophilic inflammation. Therefore, we sought to characterize the differential effects of BET inhibitor versus corticosteroids, and their potential synergism in cockroach allergen extract (CE)-induced mixed granulocytic (eosinophilic and neutrophilic) mouse model of asthma having Th2/Th17 endotype. Effects of BET inhibitor, (+)JQ-1 alone and in combination with dexamethasone (Dexa) were assessed on airway inflammation as well as Th2/Th17 related airway immune responses in CE-induced mixed granulocytic asthma. Markers of steroid resistance [histone deacetylase 2 (HDAC2), and oxidative stress] were also assessed in the lungs of mice and primary human bronchial epithelial cells (HBECs). BET inhibitor, (+)JQ-1 abolished Th17 driven neutrophilic inflammation in CE-induced mixed granulocytic asthma. Dexa had limited effect on overall airway inflammation despite having significant reductions in Th2 driven immune responses. Howev...Continue Reading

References

Aug 11, 2001·Science·T Jenuwein, C D Allis
Sep 7, 2001·The Journal of Allergy and Clinical Immunology·S MoletJ Chakir
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Aug 3, 2002·American Journal of Respiratory and Critical Care Medicine·Kazuhiro ItoIan M Adcock
Dec 24, 2002·American Journal of Respiratory Cell and Molecular Biology·Peter W HellingsJan L Ceuppens
Jan 18, 2003·The Journal of Allergy and Clinical Immunology·Ahmad NadeemHanumanthrao G Raj
Jul 9, 2003·The Journal of Allergy and Clinical Immunology·Elizabeth C MatsuiPeyton A Eggleston
Apr 15, 2004·Allergy·Matthew MasoliUNKNOWN Global Initiative for Asthma (GINA) Program
Apr 17, 2004·American Journal of Respiratory and Critical Care Medicine·Borja G CosíoIan M Adcock
Jan 21, 2006·Respirology : Official Journal of the Asian Pacific Society of Respirology·Jodie L SimpsonPeter G Gibson
Jul 15, 2006·Chest·Sidney S Braman
May 14, 2008·American Journal of Respiratory Cell and Molecular Biology·Kazuhiro ItoRakesh K Kumar
Sep 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura McKinleyJay K Kolls
Sep 13, 2008·American Journal of Respiratory and Critical Care Medicine·Hidefumi WakashinHiroshi Nakajima
Oct 18, 2008·American Journal of Respiratory Cell and Molecular Biology·David AdenugaIrfan Rahman
Apr 14, 2009·The Journal of Allergy and Clinical Immunology·Wisam Al-RamliQutayba Hamid
Jun 2, 2009·Lancet·Peter J Barnes, Ian M Adcock
Aug 8, 2009·American Journal of Respiratory and Critical Care Medicine·Rhonda H WilsonDonald N Cook
Oct 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tomoyuki FujisawaReen Wu
Sep 28, 2010·Nature·Panagis FilippakopoulosJames E Bradner
Jan 19, 2011·Chembiochem : a European Journal of Chemical Biology·Samuel S Oliver, John M Denu
Jan 29, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Narcy G ArizmendiHarissios Vliagoftis
Aug 11, 2011·The European Respiratory Journal·G J ZijlstraI H Heijink
Mar 7, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laurent L ReberKarolien De Bosscher
Aug 23, 2012·Proceedings of the National Academy of Sciences of the United States of America·Hozefa S BandukwalaAnjana Rao
Jan 8, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Satoshi AnoNobuyuki Hizawa
Jan 31, 2013·The Journal of Allergy and Clinical Immunology·Peter J Barnes
Feb 20, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anna C BelkinaGerald V Denis
Aug 28, 2013·Thorax·Irene HeijinkMaarten van den Berge
Oct 9, 2013·The Journal of Experimental Medicine·Deanna A MeleJose M Lora
Oct 30, 2013·European Journal of Immunology·Bart N Lambrecht, Hamida Hammad
Dec 21, 2013·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·L P GunawardhanaK J Baines
Apr 16, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Charalambos MichaeloudesKian Fan Chung
May 9, 2014·Respirology : Official Journal of the Asian Pacific Society of Respirology·Rebecca A MartinMatthew E Poynter
Aug 31, 2014·The Journal of Allergy and Clinical Immunology·Bart N Lambrecht, Hamida Hammad
May 2, 2015·The Journal of Allergy and Clinical Immunology·Md Ashik UllahSimon Phipps
Jul 8, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ahmed NadeemShakir D Al-Sharary
Aug 28, 2015·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·M AsaduzzamanH Vliagoftis
Jan 6, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michelle L ManniJohn F Alcorn

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Citations

Nov 30, 2019·Frontiers in Pharmacology·Jose Luis Morgado-PascualMarta Ruiz-Ortega
Sep 26, 2020·Frontiers in Immunology·Bilal Alashkar AlhamweHolger Garn
Jan 20, 2021·Signal Transduction and Targeted Therapy·Nian WangRui Kang
Sep 28, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ahmed NadeemMohammed M Al-Harbi

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