Exposure to intermittent hypoxia inhibits allergic airway inflammation in a murine model of asthma
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Obesity increases the severity of asthma, and patients with severe asthma are often complicated with obstructive sleep apnea syndrome (OSAS), a concomitant disease of obesity. We investigated whether intermittent hypoxia (IH), which is a physiological feature of OSAS, modifies allergic airway inflammation in a murine model of asthma.
Balb/c mice were sensitized by ovalbumin (OVA) intraperitoneally twice (days 1 and 14) and challenged with intranasal OVA three times (days 21, 22, and 23). The mice were exposed to IH either from days 1 to 24 (long exposure) or only from days 21 to 24 (short exposure). The impact of IH exposure to allergic airway inflammation was investigated using these mice models by histologic, morphometric, and molecular techniques. Additionally, the airway responsiveness to acetylcholine was also assessed.
OVA-sensitized and OVA-challenged mice exposed to room air (RA) showed increased total cell and eosinophil numbers in the BALF. The levels of interleukin (IL)-5 and IL-13 in the BALF also increased and goblet cell metaplasia was induced. In contrast, both long and short exposure to IH inhibited the increased total cell and eosinophil numbers. The levels of IL-5 and IL-13 in the BALF also decreased on exposure to IH. Moreover, the goblet cell hyperplasia and airway hyperresponsiveness were significantly reduced in mice exposed to IH compared to those exposed to RA.
These results suggest that IH may not deteriorate the asthmatic condition in a murine model of asthma.
KeywordsAllergic airway inflammation Animal model Asthma Intermittent hypoxia Sleep apnea syndrome
We would like to thank Kyoko Inui and Manami Matsuda for their skillful technical assistance. We would also like to thank Editage (www.editage.jp) for English language editing.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.
- 10.Alkhalil M, Schulman E, Getsy J (2009) Obstructive sleep apnea syndrome and asthma: what are the links? J Clin Sleep Med 5(1):71–79Google Scholar
- 24.Nadeem R, Molnar J, Madbouly EM, Nida M, Aggarwal S, Sajid H, Naseem J, Loomba R (2013) Serum inflammatory markers in obstructive sleep apnea: a meta-analysis. J Clin Sleep Med 9(10):1003–1012Google Scholar
- 26.Arnaud C, Beguin PC, Lantuejoul S, Pépin JL, Guillermet C, Pelli G, Burger F, Buatois V, Ribuot C, Baguet JP, Mach F, Lévy P, Dematteis M (2011) The inflammatory preatherosclerotic remodeling induced by intermittent hypoxia is attenuated by RANTES/CCL5 inhibition. Am J Respir Crit Care Med 184:724–731CrossRefGoogle Scholar
- 33.Yamashita N, Sekine K, Miyasaka T, Kawashima R, Nakajima Y, Nakano J, Yamamoto T, Horiuchi T, Hirai K, Ohta K (2001) Platelet-derived growth factor is involved in the augmentation of airway responsiveness through remodeling of airways in diesel exhaust particulate-treated mice. J Allergy Clin Immunol 107:135–142CrossRefGoogle Scholar
- 39.Raghuraman G, Rai V, Peng YJ, Prabhakar NR, Kumar GK (2009) Pattern-specific sustained activation of tyrosine hydroxylase by intermittent hypoxia: role of reactive oxygen species-dependent downregulation of protein phosphatase 2A and upregulation of protein kinases. Antioxid Redox Signal 11(8):1777–1789CrossRefGoogle Scholar