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

• Published in: Respiratory research Vol. 19; no. 1; pp. 52 - 12
• Main Authors: Aizawa, Hiroyuki, Koarai, Akira, Shishikura, Yutaka, Yanagisawa, Satoru, Yamaya, Mutsuo, Sugiura, Hisatoshi, Numakura, Tadahisa, Yamada, Mitsuhiro, Ichikawa, Tomohiro, Fujino, Naoya, Noda, Masafumi, Okada, Yoshinori, Ichinose, Masakazu
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 27.03.2018; BioMed Central; BMC
• Subjects: Aged; Antiviral Agents - toxicity; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - physiology; COPD; Development and progression; Dose-Response Relationship, Drug; Exacerbation; Female; Gene Expression; Genetic aspects; Humans; Hydrogen Peroxide - toxicity; IL-33; Interleukin-33 - biosynthesis; Interleukin-33 - genetics; Interleukins; Lung diseases, Obstructive; Male; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Middle Aged; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Physiological aspects; Poly I-C - toxicity; Respiratory Mucosa - drug effects; Respiratory Mucosa - metabolism; Respiratory Mucosa - virology; Rhinovirus - drug effects; Rhinovirus - physiology; Viral infection; Japan; Exacerbation; Oxidative stress; IL-33; Viral infection; COPD
• ISSN: 1465-993X; 1465-9921; 1465-993X
• DOI: 10.1186/s12931-018-0752-9

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. The involvement of oxidative stress in the expression of IL-33, and its signal pathway was examined after stimulation with hydrogen peroxide (H O ), 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. Treatment with H O 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 H O -potentiated IL-33 expression. In addition, H O significantly potentiated the poly (I:C)- or rhinovirus-stimulated IL-33 expression. In HBECs from healthy subjects, H O -potentiated IL-33 expression and its reversal by NAC was also confirmed. Under the condition without H O -stimulation, treatment with NAC significantly decreased the expression of IL-33 in HBECs from COPD patients, but not in those from healthy subjects. 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.