Intermittent hypoxic pretreatment exacerbates house dust mite‐induced asthma airway inflammation

• Published in: Immunity, Inflammation and Disease Vol. 12; no. 4; pp. e1253 - n/a
• Main Authors: Meng, Hao, Zhang, Dongxue, Que, Yifan, Hu, Peng, Wang, Runsheng, Liao, Yunfei, Xu, Guogang
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.04.2024; John Wiley and Sons Inc; Wiley
• Subjects: Airway management; Allergens; Allergens - therapeutic use; Allergies; Animals; Asthma; Asthma - drug therapy; Chronic obstructive pulmonary disease; Dermatophagoides pteronyssinus; Females; Hypoxia; Inflammation; intermittent hypoxic preconditioning; Laboratory animals; Mice; NF-kappa B; NF‐κBTh2 inflammatory response; Original; Ostomy; Pulmonary arteries; Pyroglyphidae; Respiratory Hypersensitivity; Smooth muscle; Beijing China; China; intermittent hypoxic preconditioning; NF‐κBTh2 inflammatory response; asthma
• ISSN: 2050-4527; 2050-4527
• DOI: 10.1002/iid3.1253

Background Asthma is widely recognized as an inflammatory disorder. In the context of this inflammatory microenvironment, the involvement of hypoxia and its impact on related pathways have drawn considerable attention. However, the exact role of hypoxia, a prevalent environmental factor, in the development and progression of asthma remains poorly understood. Methods Mice were treated with house dust mite (HDM) extracts for 23 days to induce asthma. Mice were divided into room air (RA) group and intermittent hypoxic (IH) group by exposing to different conditions and IH preconditioning (IHP) were underwent to the above groups before the hypoxic regimen. Airway inflammation in mice was evaluated by airway hyperresponsiveness, excessive mucus secretion, and recruitment of inflammatory cells. Immunohistochemistry was employed to quantify the expression levels of NF‐κB. Subsequently, the dose of allergen was modified to investigate whether the impact of hypoxia on asthma is affected by different doses of allergens. Result Compared to the RA and IH groups, HDM‐treated mice in the IHP group exhibited aggravated inflammatory cell infiltration and airway hyperresponsiveness (p＜.05). Moreover, there was an increased release of inflammatory mediators and higher expression levels of NF‐κB (p＜.05). Importantly, the impact ia on asthma was found to be influenced by high dose of allergen (p＜.05). Conclusion IHP treatment potentially exacerbates HDM‐induced airway inflammation in asthma, with the involvement of NF‐κB, particularly under high‐dose allergen stimulation. Our findings suggest that IHP may enhance TH2 inflammatory responses through the NF‐κB pathway, leading to exacerbated airway inflammation, increased airway hyperresponsiveness, and ultimately worsening of asthma symptoms. These results provide novel insights into the impact of a hypoxic environment on asthma development and offer a basis for developing intervention strategies targeting asthma under low oxygen conditions.