Chronic Intermittent Hypoxia Reduces the Effects of Glucosteroid in Asthma via Activating the p38 MAPK Signaling Pathway
AimsObstructive sleep apnea (OSA) is a risk factor for steroid-resistant (SR) asthma. However, the underlying mechanism is not well defined. This study aimed to investigate how chronic intermittent hypoxia (CIH), the main pathophysiology of OSA, influenced the effects of glucocorticoids (GCs) on ast...
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doaj-a6dc93eca47345d6a8f084d83498821d2021-09-03T12:12:26ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-08-011210.3389/fphys.2021.703281703281Chronic Intermittent Hypoxia Reduces the Effects of Glucosteroid in Asthma via Activating the p38 MAPK Signaling PathwayLi Liang0Li Liang1Xin Gu2Hai Ji Shen3Yu Heng Shi4Yao Li5Jie Zhang6Yan Yan Chen7Zhen He Chen8Jia Yun Ma9Qing Yun Li10Department of Respiratory and Critical Care Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Urology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaAimsObstructive sleep apnea (OSA) is a risk factor for steroid-resistant (SR) asthma. However, the underlying mechanism is not well defined. This study aimed to investigate how chronic intermittent hypoxia (CIH), the main pathophysiology of OSA, influenced the effects of glucocorticoids (GCs) on asthma.Main MethodsThe effects of dexamethasone (Dex) were determined using the ovalbumin (OVA)-challenged mouse model of asthma and transforming growth factor (TGF)-β treated airway smooth muscle cells (ASMCs), with or without CIH. The p38 MAPK signaling pathway activity was then detected in the mouse (n = 6) and ASMCs models (n = 6), which were both treated with the p38 MAPK inhibitor SB239063.Key FindingsUnder CIH, mouse pulmonary resistance value, inflammatory cells in bronchoalveolar lavage fluid (BALF), and inflammation scores increased in OVA-challenged combined with CIH exposure mice compared with OVA-challenged mice (p < 0.05). These indicators were similarly raised in the OVA + CIH + Dex group compared with the OVA + Dex group (P < 0.05). CIH exposure enhanced the activation of the p38 MAPK pathway, oxidative stress injury, and the expression of NF-κB both in lung tissue and ASMCs, which were reversed by treatment with Dex and SB239063. In the in vitro study, treatment with Dex and SB239063 decreased ASMCs proliferation induced by TGF-β combined with CIH and suppressed activation of the p38 MAPK pathway, oxidative stress injury, and NF-κB nuclear transcription (p < 0.05).SignificanceThese results indicated that CIH decreased GC sensitivity by activating the p38 MAPK signaling pathway.https://www.frontiersin.org/articles/10.3389/fphys.2021.703281/fullp38 MAPK pathwayovalbuminchronic intermittent hypoxiaasthmaglucosteroid |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Li Liang Li Liang Xin Gu Hai Ji Shen Yu Heng Shi Yao Li Jie Zhang Yan Yan Chen Zhen He Chen Jia Yun Ma Qing Yun Li |
spellingShingle |
Li Liang Li Liang Xin Gu Hai Ji Shen Yu Heng Shi Yao Li Jie Zhang Yan Yan Chen Zhen He Chen Jia Yun Ma Qing Yun Li Chronic Intermittent Hypoxia Reduces the Effects of Glucosteroid in Asthma via Activating the p38 MAPK Signaling Pathway Frontiers in Physiology p38 MAPK pathway ovalbumin chronic intermittent hypoxia asthma glucosteroid |
author_facet |
Li Liang Li Liang Xin Gu Hai Ji Shen Yu Heng Shi Yao Li Jie Zhang Yan Yan Chen Zhen He Chen Jia Yun Ma Qing Yun Li |
author_sort |
Li Liang |
title |
Chronic Intermittent Hypoxia Reduces the Effects of Glucosteroid in Asthma via Activating the p38 MAPK Signaling Pathway |
title_short |
Chronic Intermittent Hypoxia Reduces the Effects of Glucosteroid in Asthma via Activating the p38 MAPK Signaling Pathway |
title_full |
Chronic Intermittent Hypoxia Reduces the Effects of Glucosteroid in Asthma via Activating the p38 MAPK Signaling Pathway |
title_fullStr |
Chronic Intermittent Hypoxia Reduces the Effects of Glucosteroid in Asthma via Activating the p38 MAPK Signaling Pathway |
title_full_unstemmed |
Chronic Intermittent Hypoxia Reduces the Effects of Glucosteroid in Asthma via Activating the p38 MAPK Signaling Pathway |
title_sort |
chronic intermittent hypoxia reduces the effects of glucosteroid in asthma via activating the p38 mapk signaling pathway |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2021-08-01 |
description |
AimsObstructive sleep apnea (OSA) is a risk factor for steroid-resistant (SR) asthma. However, the underlying mechanism is not well defined. This study aimed to investigate how chronic intermittent hypoxia (CIH), the main pathophysiology of OSA, influenced the effects of glucocorticoids (GCs) on asthma.Main MethodsThe effects of dexamethasone (Dex) were determined using the ovalbumin (OVA)-challenged mouse model of asthma and transforming growth factor (TGF)-β treated airway smooth muscle cells (ASMCs), with or without CIH. The p38 MAPK signaling pathway activity was then detected in the mouse (n = 6) and ASMCs models (n = 6), which were both treated with the p38 MAPK inhibitor SB239063.Key FindingsUnder CIH, mouse pulmonary resistance value, inflammatory cells in bronchoalveolar lavage fluid (BALF), and inflammation scores increased in OVA-challenged combined with CIH exposure mice compared with OVA-challenged mice (p < 0.05). These indicators were similarly raised in the OVA + CIH + Dex group compared with the OVA + Dex group (P < 0.05). CIH exposure enhanced the activation of the p38 MAPK pathway, oxidative stress injury, and the expression of NF-κB both in lung tissue and ASMCs, which were reversed by treatment with Dex and SB239063. In the in vitro study, treatment with Dex and SB239063 decreased ASMCs proliferation induced by TGF-β combined with CIH and suppressed activation of the p38 MAPK pathway, oxidative stress injury, and NF-κB nuclear transcription (p < 0.05).SignificanceThese results indicated that CIH decreased GC sensitivity by activating the p38 MAPK signaling pathway. |
topic |
p38 MAPK pathway ovalbumin chronic intermittent hypoxia asthma glucosteroid |
url |
https://www.frontiersin.org/articles/10.3389/fphys.2021.703281/full |
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