IRF3 and IRF7 contribute to diesel exhaust particles-induced pulmonary inflammation by mediating mTORC1 activation and restraining autophagy in mice

European Journal of Immunology
Chaoming WangXiaopeng Qi

Abstract

Exposure to diesel exhaust particles (DEPs) is associated with acute inflammatory responses in the lung and exacerbation of respiratory diseases. However, the mechanism by which DEPs trigger the inflammatory responses remains unclear. Here, we demonstrated that the interferon response factors IRF3 and IRF7 played pivotal roles in DEP-induced pulmonary inflammation. DEPs could not directly induce inflammatory cytokine expression in mouse cells, whereas DEPs triggered autophagy both in vitro and in vivo. The DEP-induced autophagy was augmented in the absence of IRF3 and IRF7, but not in the absence of IFNAR. The expression of Raptor was induced by IRF3 and IRF7 in response to DEPs treatment. Furthermore, administration of the mechanistic target of rapamycin (mTOR) inhibitor alleviated the inflammatory responses in the lung during DEP exposure. Our findings define an IFNAR-independent role of increased autophagy in the absence of IRF3 and IRF7 during pulmonary DEP exposure, and provide the basis to develop new therapeutic approaches to counteract the adverse effects of DEPs and possibly other ambient particulate matters. This article is protected by copyright. All rights reserved.

References

Jan 23, 2004·Toxicological Sciences : an Official Journal of the Society of Toxicology·Chen-Chen LeeJaw-Jou Kang
Feb 8, 2005·The Journal of Allergy and Clinical Immunology·Marc Riedl, David Diaz-Sanchez
Jun 19, 2008·Environmental Health Perspectives·Albino Barraza-VillarrealIsabelle Romieu
Jan 21, 2009·The Journal of Allergy and Clinical Immunology·John R BalmesPaul D Blanc
Jan 20, 2010·FEBS Letters·Chang Hwa JungDo-Hyung Kim
Aug 3, 2010·The Journal of Allergy and Clinical Immunology·Thomas MarichalChristophe J Desmet
Jan 21, 2011·Nature·Beth LevineHerbert W Virgin
Aug 17, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sharen ProvoostKurt G Tournoy
Aug 24, 2011·Journal of Toxicology·Maura Lodovici, Elisabetta Bigagli
Oct 5, 2011·The American Journal of Pathology·Jiyoun KimDaniel G Remick
Oct 19, 2011·The American Journal of Pathology·Nicholas Kenyon, Fu-Tong Liu
Jul 10, 2012·Particle and Fibre Toxicology·Dai-Hua TsaiMurielle Bochud
Dec 12, 2012·American Journal of Respiratory Cell and Molecular Biology·Juan C CaraballoAlejandro P Comellas
Mar 20, 2013·BioMed Research International·P E SchwarzeJ Øvrevik
Sep 26, 2013·The Journal of Allergy and Clinical Immunology·Eric B BrandtGurjit K Khurana Hershey
Dec 24, 2013·Nature Reviews. Immunology·Lionel B Ivashkiv, Laura T Donlin
May 6, 2014·Lancet·Michael Guarnieri, John R Balmes
Jul 13, 2014·Cellular and Molecular Life Sciences : CMLS·Dan EhningerKan Xie
Sep 18, 2014·Journal of Exposure Science & Environmental Epidemiology·Richard W AtkinsonH Ross Anderson
Sep 27, 2014·Cell Death and Differentiation·G FilomeniF Cecconi
Jan 17, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sharen ProvoostGuy F Joos
Mar 1, 2016·Allergy, Asthma & Immunology Research·Byeong Gon KimAn Soo Jang
Jun 19, 2016·The Journal of Allergy and Clinical Immunology·Katrien C De GroveGuy F Joos
Sep 17, 2016·F1000Research·Jianling XieChristopher G Proud
Nov 8, 2016·Nature·Juan LinManolis Pasparakis
Nov 8, 2016·Nature·Kim NewtonVishva M Dixit
Oct 25, 2017·American Journal of Respiratory and Critical Care Medicine·Nirav R BhaktaPrescott G Woodruff
Nov 18, 2017·Annual Review of Immunology·Yu Matsuzawa-IshimotoKen Cadwell
Jan 21, 2018·Cell Death and Differentiation·Yang LiXiaopeng Qi
Jan 24, 2018·Nucleic Acids Research·Kellen K AndrilenasTrevor Siggers
Jun 20, 2018·The Journal of Clinical Investigation·Fubing LiXiaopeng Qi
Oct 22, 2019·European Journal of Immunology·Andrea CossarizzaArturo Zychlinsky

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Related Concepts

Related Feeds

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms