期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 323, 期 6, 页码 R921-R934出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00213.2022
关键词
adiponectin; airway hyperresponsiveness; asthma; coefficient of lung tissue elastance; interleukin-11
类别
资金
- National Institute of Environmental Health Sciences of the National Institutes of Health [R03ES022378, R03ES024883]
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R03AI107432]
Deficiency of IL-11R alpha 1 attenuates lung inflammation and decreases airway responsiveness to methacholine in a mouse model of nonatopic asthma.
Interleukin (IL)-11, a multifunctional cytokine, contributes to numerous biological processes, including adipogenesis, hematopoiesis, and inflammation. Asthma, a respiratory disease, is notably characterized by reversible airway obstruction, persistent lung inflammation, and airway hyperresponsiveness (AHR). Nasal insufflation of IL-11 causes AHR in wild-type mice while lung inflammation induced by antigen sensitization and challenge, which mimics features of atopic asthma in humans, is attenuated in mice genetically deficient in IL-11 receptor subunit alpha-1 (IL-11R alpha 1-deficient mice), a transmembrane receptor that is required conjointly with glycoprotein 130 to transduce IL-11 signaling. Nevertheless, the contribution of IL-11R alpha 1 to characteristics of nonatopic asthma is unknown. Thus, based on the aforementioned observations, we hypothesized that genetic deficiency of IL-11R alpha 1 attenuates lung inflammation and increases airway responsiveness after acute inhalation exposure to ozone (O-3), a criteria pollutant and nonatopic asthma stimulus. Accordingly, 4 and/or 24 h after cessation of exposure to filtered room air or O-3, we assessed lung inflammation and airway responsiveness in wild-type and IL-11R alpha 1-deficient mice. With the exception of bronchoalveolar lavage macrophages and adiponectin, which were significantly increased and decreased, respectively, in O-3-exposed IL-11R alpha 1-deficient as compared with O-3-exposed wild-type mice, no other genotype-related differences in lung inflammation indices that we quantified were observed in O-3-exposed mice. However, airway responsiveness to acetyl-beta-methylcholine chloride (methacholine) was significantly diminished in IL-11R alpha 1-deficient as compared with wild-type mice after O-3 exposure. In conclusion, these results demonstrate that IL-11R alpha 1 minimally contributes to lung inflammation but is required for maximal airway responsiveness to methacholine in a mouse model of nonatopic asthma.
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