Oxidative stress enhances the expression of IL-33 in human airway epithelial cells.

Abstract

BACKGROUND:

Interleukin-33 (IL-33) is a cytokine belonging to the IL-1 family, and its possible involvement in the pathophysiology of COPD and viral-induced exacerbations has been demonstrated. IL-33 has been shown to be increased in the airway epithelial cells from COPD patients, but the regulating mechanism of IL-33 expression in airway epithelial cells remains largely unknown. In the current study, we examined whether oxidative stress, which participates in the pathogenesis of COPD, affects the expression of IL-33 in airway epithelial cells and also evaluated the effect during viral infection.

METHODS:

The involvement of oxidative stress in the expression of IL-33, and its signal pathway was examined after stimulation with hydrogen peroxide (H2O2), with or without stimulation by polyinosinic-polycytidylic acid [poly (I:C)], a synthetic analogue of dsRNA that mimics viral infection, or rhinovirus infection in NCI-H292 cells and primary human bronchial epithelial cells (HBECs). In addition, the effect of antioxidant, N-acetylcysteine (NAC) in the expression of IL-33 was compared between HBECs from healthy subjects and those from COPD patients.

RESULTS:

Treatment with H2O2 significantly potentiated IL-33 expression in NCI-H292 cells, and the potentiation was reversed by NAC treatment. Mitogen-activated protein kinase (MAPK) inhibitors, but not nuclear factor-kappa B inhibitors, also significantly decreased the H2O2-potentiated IL-33 expression. In addition, H2O2 significantly potentiated the poly (I:C)- or rhinovirus-stimulated IL-33 expression. In HBECs from healthy subjects, H2O2-potentiated IL-33 expression and its reversal by NAC was also confirmed. Under the condition without H2O2-stimulation, treatment with NAC significantly decreased the expression of IL-33 in HBECs from COPD patients, but not in those from healthy subjects.

CONCLUSIONS:

These results demonstrate that oxidative stress involves in the expression of IL-33 in airway epithelial cells via MAPK signal pathway and it augments IL-33 expression during viral infection. This mechanism may participate in the regulation of IL-33 expression in airway epithelial cells in COPD and the viral-induced exacerbations. Modulation of this pathway could become a therapeutic target for viral-induced exacerbations of COPD.

• Authors: Hiroyuki Aizawa, Akira Koarai, Yutaka Shishikura, Satoru Yanagisawa, Mutsuo Yamaya, Hisatoshi Sugiura, Tadahisa Numakura, Mitsuhiro Yamada, Tomohiro Ichikawa, Naoya Fujino, Masafumi Noda, Yoshinori Okada, Masakazu Ichinose
• Journal: Respiratory research (Respir Res) Vol. 19 Issue 1 Pg. 52 (03 27 2018) ISSN: 1465-993X [Electronic] England
• PMID: 29587772 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• IL33 protein, human
• Interleukin-33
• Hydrogen Peroxide
• Poly I-C

Topics

• Aged
• Antiviral Agents (toxicity)
• Cell Line, Tumor
• Cell Survival (drug effects, physiology)
• Dose-Response Relationship, Drug
• Female
• Gene Expression
• Humans
• Hydrogen Peroxide (toxicity)
• Interleukin-33 (biosynthesis, genetics)
• MAP Kinase Signaling System (drug effects, physiology)
• Male
• Middle Aged
• Oxidative Stress (drug effects, physiology)
• Poly I-C (toxicity)
• Respiratory Mucosa (drug effects, metabolism, virology)
• Rhinovirus (drug effects, physiology)