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 re...
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doaj-22e130c82d2543998c8d2a045b551b942020-11-25T00:02:19ZengBMCRespiratory Research1465-993X2018-03-0119111210.1186/s12931-018-0752-9Oxidative stress enhances the expression of IL-33 in human airway epithelial cellsHiroyuki Aizawa0Akira Koarai1Yutaka Shishikura2Satoru Yanagisawa3Mutsuo Yamaya4Hisatoshi Sugiura5Tadahisa Numakura6Mitsuhiro Yamada7Tomohiro Ichikawa8Naoya Fujino9Masafumi Noda10Yoshinori Okada11Masakazu Ichinose12Department of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineAbstract 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.http://link.springer.com/article/10.1186/s12931-018-0752-9COPDExacerbationIL-33Oxidative stressViral infection |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Oxidative stress enhances the expression of IL-33 in human airway epithelial cells Respiratory Research COPD Exacerbation IL-33 Oxidative stress Viral infection |
author_facet |
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 |
author_sort |
Hiroyuki Aizawa |
title |
Oxidative stress enhances the expression of IL-33 in human airway epithelial cells |
title_short |
Oxidative stress enhances the expression of IL-33 in human airway epithelial cells |
title_full |
Oxidative stress enhances the expression of IL-33 in human airway epithelial cells |
title_fullStr |
Oxidative stress enhances the expression of IL-33 in human airway epithelial cells |
title_full_unstemmed |
Oxidative stress enhances the expression of IL-33 in human airway epithelial cells |
title_sort |
oxidative stress enhances the expression of il-33 in human airway epithelial cells |
publisher |
BMC |
series |
Respiratory Research |
issn |
1465-993X |
publishDate |
2018-03-01 |
description |
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. |
topic |
COPD Exacerbation IL-33 Oxidative stress Viral infection |
url |
http://link.springer.com/article/10.1186/s12931-018-0752-9 |
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