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

Abstract

BACKGROUND:

IL-33 plays a critical role in regulation of tissue homeostasis, injury, and repair. Whether IL-33 regulates neutrophil recruitment and functions independently of airways hyperresponsiveness (AHR) in the setting of ozone-induced lung injury and inflammation is unclear.

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.

• Authors: Chloé Michaudel, Claire Mackowiak, Isabelle Maillet, Louis Fauconnier, Cezmi A Akdis, Milena Sokolowska, Anita Dreher, Hern-Tze Tina Tan, Valérie F Quesniaux, Bernhard Ryffel, Dieudonnée Togbe
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 142 Issue 3 Pg. 942-958 (09 2018) ISSN: 1097-6825 [Electronic] United States
• PMID: 29331644 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Air Pollutants
• Il1rl1 protein, mouse
• Il33 protein, mouse
• Interleukin-1 Receptor-Like 1 Protein
• Interleukin-33
• Oxidants
• Ozone

Topics

• Air Pollutants (toxicity)
• Animals
• Female
• Inflammation (chemically induced, immunology, pathology)
• Interleukin-1 Receptor-Like 1 Protein (immunology)
• Interleukin-33 (immunology)
• Lung (drug effects, immunology, pathology)
• Lung Injury (chemically induced, immunology, pathology)
• Mice, Inbred C57BL
• Mice, Knockout
• Neutrophils (drug effects, immunology)
• Oxidants (toxicity)
• Ozone (toxicity)