Oxidative stress serves as a key checkpoint for IL-33 release by airway epithelium

M. Uchida, E. L. Anderson, D. L. Squillace, Nandadevi Patil, Peter J Maniak, K. Iijima, H. Kita, Scott M O'Grady

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: Interleukin (IL)-33 is implicated in the pathophysiology of asthma and allergic diseases. However, our knowledge is limited regarding how IL-33 release is controlled. The transcription factor nuclear factor-erythroid-2-related factor 2 (Nrf2) plays a key role in antioxidant response regulation. Objective: The goal of this project was to investigate the role of cellular oxidative stress in controlling IL-33 release in airway epithelium. Methods: Complementary approaches were used that included human bronchial epithelial cells and mouse models of airway type-2 immunity that were exposed to fungus Alternaria extract. The clinically available Nrf2 activator 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid methyl ester (CDDO-Me) was used to evaluate the role of Nrf2-induced antioxidant molecules. Results: Human bronchial epithelial cells produced reactive oxygen species (ROS) when they were exposed to Alternaria extract. ROS scavengers, such as glutathione (GSH) and N-acetyl cysteine, prevented extracellular secretion of ATP and increases in intracellular calcium concentrations that precede IL-33 release. Administration of CDDO-Me to mice enhanced expression of a number of antioxidant molecules in the lungs and elevated lung levels of endogenous GSH. Importantly, CDDO-Me treatment reduced allergen-induced ATP secretion and IL-33 release by airway epithelial cells in vitro and protected mice from IL-33 release and asthma-like pathological changes in the lungs. Conclusions: The balance between oxidative stress and antioxidant responses plays a key role in controlling IL-33 release in airway epithelium. The therapeutic potential of Nrf2 activators needs to be considered for asthma and allergic airway diseases.

Original languageEnglish (US)
Pages (from-to)1521-1531
Number of pages11
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume72
Issue number10
DOIs
StatePublished - Oct 1 2017

Fingerprint

Oxidative Stress
Epithelium
Antioxidants
Alternaria
Esters
Asthma
Epithelial Cells
Lung
Acids
Reactive Oxygen Species
NF-E2 Transcription Factor
Adenosine Triphosphate
Allergens
Cysteine
Interleukin-33
Immunity
Fungi
Calcium
N-acetylglutathione
Therapeutics

Keywords

  • IL-33
  • airway epithelial cells
  • asthma
  • lung
  • nuclear factor-erythroid-2-related factor 2
  • reactive oxygen species

Cite this

Oxidative stress serves as a key checkpoint for IL-33 release by airway epithelium. / Uchida, M.; Anderson, E. L.; Squillace, D. L.; Patil, Nandadevi; Maniak, Peter J; Iijima, K.; Kita, H.; O'Grady, Scott M.

In: Allergy: European Journal of Allergy and Clinical Immunology, Vol. 72, No. 10, 01.10.2017, p. 1521-1531.

Research output: Contribution to journalArticle

@article{083322872d47482a8f34883d2a9b9590,
title = "Oxidative stress serves as a key checkpoint for IL-33 release by airway epithelium",
abstract = "Background: Interleukin (IL)-33 is implicated in the pathophysiology of asthma and allergic diseases. However, our knowledge is limited regarding how IL-33 release is controlled. The transcription factor nuclear factor-erythroid-2-related factor 2 (Nrf2) plays a key role in antioxidant response regulation. Objective: The goal of this project was to investigate the role of cellular oxidative stress in controlling IL-33 release in airway epithelium. Methods: Complementary approaches were used that included human bronchial epithelial cells and mouse models of airway type-2 immunity that were exposed to fungus Alternaria extract. The clinically available Nrf2 activator 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid methyl ester (CDDO-Me) was used to evaluate the role of Nrf2-induced antioxidant molecules. Results: Human bronchial epithelial cells produced reactive oxygen species (ROS) when they were exposed to Alternaria extract. ROS scavengers, such as glutathione (GSH) and N-acetyl cysteine, prevented extracellular secretion of ATP and increases in intracellular calcium concentrations that precede IL-33 release. Administration of CDDO-Me to mice enhanced expression of a number of antioxidant molecules in the lungs and elevated lung levels of endogenous GSH. Importantly, CDDO-Me treatment reduced allergen-induced ATP secretion and IL-33 release by airway epithelial cells in vitro and protected mice from IL-33 release and asthma-like pathological changes in the lungs. Conclusions: The balance between oxidative stress and antioxidant responses plays a key role in controlling IL-33 release in airway epithelium. The therapeutic potential of Nrf2 activators needs to be considered for asthma and allergic airway diseases.",
keywords = "IL-33, airway epithelial cells, asthma, lung, nuclear factor-erythroid-2-related factor 2, reactive oxygen species",
author = "M. Uchida and Anderson, {E. L.} and Squillace, {D. L.} and Nandadevi Patil and Maniak, {Peter J} and K. Iijima and H. Kita and O'Grady, {Scott M}",
year = "2017",
month = "10",
day = "1",
doi = "10.1111/all.13158",
language = "English (US)",
volume = "72",
pages = "1521--1531",
journal = "Allergy: European Journal of Allergy and Clinical Immunology",
issn = "0105-4538",
publisher = "Wiley-Blackwell",
number = "10",

}

TY - JOUR

T1 - Oxidative stress serves as a key checkpoint for IL-33 release by airway epithelium

AU - Uchida, M.

AU - Anderson, E. L.

AU - Squillace, D. L.

AU - Patil, Nandadevi

AU - Maniak, Peter J

AU - Iijima, K.

AU - Kita, H.

AU - O'Grady, Scott M

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Background: Interleukin (IL)-33 is implicated in the pathophysiology of asthma and allergic diseases. However, our knowledge is limited regarding how IL-33 release is controlled. The transcription factor nuclear factor-erythroid-2-related factor 2 (Nrf2) plays a key role in antioxidant response regulation. Objective: The goal of this project was to investigate the role of cellular oxidative stress in controlling IL-33 release in airway epithelium. Methods: Complementary approaches were used that included human bronchial epithelial cells and mouse models of airway type-2 immunity that were exposed to fungus Alternaria extract. The clinically available Nrf2 activator 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid methyl ester (CDDO-Me) was used to evaluate the role of Nrf2-induced antioxidant molecules. Results: Human bronchial epithelial cells produced reactive oxygen species (ROS) when they were exposed to Alternaria extract. ROS scavengers, such as glutathione (GSH) and N-acetyl cysteine, prevented extracellular secretion of ATP and increases in intracellular calcium concentrations that precede IL-33 release. Administration of CDDO-Me to mice enhanced expression of a number of antioxidant molecules in the lungs and elevated lung levels of endogenous GSH. Importantly, CDDO-Me treatment reduced allergen-induced ATP secretion and IL-33 release by airway epithelial cells in vitro and protected mice from IL-33 release and asthma-like pathological changes in the lungs. Conclusions: The balance between oxidative stress and antioxidant responses plays a key role in controlling IL-33 release in airway epithelium. The therapeutic potential of Nrf2 activators needs to be considered for asthma and allergic airway diseases.

AB - Background: Interleukin (IL)-33 is implicated in the pathophysiology of asthma and allergic diseases. However, our knowledge is limited regarding how IL-33 release is controlled. The transcription factor nuclear factor-erythroid-2-related factor 2 (Nrf2) plays a key role in antioxidant response regulation. Objective: The goal of this project was to investigate the role of cellular oxidative stress in controlling IL-33 release in airway epithelium. Methods: Complementary approaches were used that included human bronchial epithelial cells and mouse models of airway type-2 immunity that were exposed to fungus Alternaria extract. The clinically available Nrf2 activator 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid methyl ester (CDDO-Me) was used to evaluate the role of Nrf2-induced antioxidant molecules. Results: Human bronchial epithelial cells produced reactive oxygen species (ROS) when they were exposed to Alternaria extract. ROS scavengers, such as glutathione (GSH) and N-acetyl cysteine, prevented extracellular secretion of ATP and increases in intracellular calcium concentrations that precede IL-33 release. Administration of CDDO-Me to mice enhanced expression of a number of antioxidant molecules in the lungs and elevated lung levels of endogenous GSH. Importantly, CDDO-Me treatment reduced allergen-induced ATP secretion and IL-33 release by airway epithelial cells in vitro and protected mice from IL-33 release and asthma-like pathological changes in the lungs. Conclusions: The balance between oxidative stress and antioxidant responses plays a key role in controlling IL-33 release in airway epithelium. The therapeutic potential of Nrf2 activators needs to be considered for asthma and allergic airway diseases.

KW - IL-33

KW - airway epithelial cells

KW - asthma

KW - lung

KW - nuclear factor-erythroid-2-related factor 2

KW - reactive oxygen species

UR - http://www.scopus.com/inward/record.url?scp=85017372490&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85017372490&partnerID=8YFLogxK

U2 - 10.1111/all.13158

DO - 10.1111/all.13158

M3 - Article

C2 - 28273344

AN - SCOPUS:85017372490

VL - 72

SP - 1521

EP - 1531

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

SN - 0105-4538

IS - 10

ER -