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Chronic Intermittent Hypoxia Reduces the Effects of Glucosteroid in Asthma via Activating the p38 MAPK Signaling

Li Liang1,2, Xin Gu3, Hai Ji Shen1

  • 1Department of Respiratory and Critical Care Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Frontiers in Physiology
|September 13, 2021
PubMed
Abstract

Insights

Chronic intermittent hypoxia (CIH), common in obstructive sleep apnea (OSA), reduces glucocorticoid (GC) effectiveness in asthma by activating the p38 MAPK pathway. This finding is crucial for understanding steroid-resistant asthma.

Area of Science:

  • Respiratory Medicine
  • Molecular Biology
  • Pathophysiology

Background:

  • Obstructive sleep apnea (OSA) is linked to steroid-resistant (SR) asthma.
  • The precise mechanisms underlying this association remain unclear.
  • Chronic intermittent hypoxia (CIH) is the primary physiological characteristic of OSA.

Purpose of the Study:

  • To investigate how CIH affects glucocorticoid (GC) treatment efficacy in asthma.
  • To elucidate the role of the p38 MAPK signaling pathway in this interaction.

Main Methods:

  • Utilized an ovalbumin (OVA)-induced mouse model of asthma and transforming growth factor-β (TGF-β) treated airway smooth muscle cells (ASMCs).
  • Exposed models to chronic intermittent hypoxia (CIH) with or without dexamethasone (Dex) treatment.
  • Assessed p38 MAPK signaling pathway activity, inflammation, oxidative stress, and NF-κB expression, using the p38 MAPK inhibitor SB239063.

Main Results:

  • CIH exacerbated asthma indicators, including pulmonary resistance and inflammation, in mice.
  • GC treatment (Dex) was less effective in the presence of CIH.
  • CIH upregulated p38 MAPK, oxidative stress, and NF-κB, effects reversed by Dex and SB239063.

Conclusions:

  • CIH diminishes GC sensitivity in asthma by activating the p38 MAPK signaling pathway.
  • Targeting the p38 MAPK pathway may offer a therapeutic strategy for SR asthma associated with OSA.
Keywords:
asthmachronic intermittent hypoxiaglucosteroidovalbuminp38 MAPK pathway

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