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Ozone exposure induces respiratory barrier biphasic injury and inflammation controlled by IL-33


Michaudel, Chloé; Mackowiak, Claire; Maillet, Isabelle; Fauconnier, Louis; Akdis, Cezmi A; Sokolowska, Milena; Dreher, Anita; Tan, Hern-Tze Tina; Quesniaux, Valérie F; Ryffel, Bernhard; Togbe, Dieudonnée (2018). Ozone exposure induces respiratory barrier biphasic injury and inflammation controlled by IL-33. Journal of Allergy and Clinical Immunology, 142(3):942-958.

Abstract

Objective We sought to examine the role of the IL-33/ST2 axis in lung inflammation on acute ozone exposure in mice.
Methods ST2- and Il33–deficient, IL-33 citrine reporter, and C57BL/6 (wild-type) mice underwent a single ozone exposure (1 ppm for 1 hour) in all studies. Cell recruitment in lung tissue and the bronchoalveolar space, inflammatory parameters, epithelial barrier damage, and airway hyperresponsiveness (AHR) were determined.
Results We report that a single ozone exposure causes rapid disruption of the epithelial barrier within 1 hour, followed by a second phase of respiratory barrier injury with increased neutrophil recruitment, reactive oxygen species production, AHR, and IL-33 expression in epithelial and myeloid cells in wild-type mice. In the absence of IL-33 or IL-33 receptor/ST2, epithelial cell injury with protein leak and myeloid cell recruitment and inflammation are further increased, whereas the tight junction proteins E-cadherin and zonula occludens 1 and reactive oxygen species expression in neutrophils and AHR are diminished. ST2 neutralization recapitulated the enhanced ozone-induced neutrophilic inflammation. However, myeloid cell depletion using GR-1 antibody reduced ozone-induced lung inflammation, epithelial cell injury, and protein leak, whereas administration of recombinant mouse IL-33 reduced neutrophil recruitment in Il33–deficient mice.
Conclusion Data demonstrate that ozone causes an immediate barrier injury that precedes myeloid cell–mediated inflammatory injury under the control of the IL-33/ST2 axis. Thus IL-33/ST2 signaling is critical for maintenance of intact epithelial barrier and inflammation.

Abstract

Objective We sought to examine the role of the IL-33/ST2 axis in lung inflammation on acute ozone exposure in mice.
Methods ST2- and Il33–deficient, IL-33 citrine reporter, and C57BL/6 (wild-type) mice underwent a single ozone exposure (1 ppm for 1 hour) in all studies. Cell recruitment in lung tissue and the bronchoalveolar space, inflammatory parameters, epithelial barrier damage, and airway hyperresponsiveness (AHR) were determined.
Results We report that a single ozone exposure causes rapid disruption of the epithelial barrier within 1 hour, followed by a second phase of respiratory barrier injury with increased neutrophil recruitment, reactive oxygen species production, AHR, and IL-33 expression in epithelial and myeloid cells in wild-type mice. In the absence of IL-33 or IL-33 receptor/ST2, epithelial cell injury with protein leak and myeloid cell recruitment and inflammation are further increased, whereas the tight junction proteins E-cadherin and zonula occludens 1 and reactive oxygen species expression in neutrophils and AHR are diminished. ST2 neutralization recapitulated the enhanced ozone-induced neutrophilic inflammation. However, myeloid cell depletion using GR-1 antibody reduced ozone-induced lung inflammation, epithelial cell injury, and protein leak, whereas administration of recombinant mouse IL-33 reduced neutrophil recruitment in Il33–deficient mice.
Conclusion Data demonstrate that ozone causes an immediate barrier injury that precedes myeloid cell–mediated inflammatory injury under the control of the IL-33/ST2 axis. Thus IL-33/ST2 signaling is critical for maintenance of intact epithelial barrier and inflammation.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Swiss Institute of Allergy and Asthma Research
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Immunology, Immunology and Allergy
Language:English
Date:1 September 2018
Deposited On:08 Mar 2019 09:12
Last Modified:25 Sep 2019 00:26
Publisher:Elsevier
ISSN:0091-6749
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.jaci.2017.11.044

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