Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia.
Division of Critical Care Medicine, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas.
Am J Physiol Regul Integr Comp Physiol. 2022 Dec 1;323(6):R921-R934. doi: 10.1152/ajpregu.00213.2022. Epub 2022 Oct 25.
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 α-1 (IL-11Rα1-deficient mice), a transmembrane receptor that is required conjointly with glycoprotein 130 to transduce IL-11 signaling. Nevertheless, the contribution of IL-11Rα1 to characteristics of nonatopic asthma is unknown. Thus, based on the aforementioned observations, we hypothesized that genetic deficiency of IL-11Rα1 attenuates lung inflammation and increases airway responsiveness after acute inhalation exposure to ozone (O), a criteria pollutant and nonatopic asthma stimulus. Accordingly, 4 and/or 24 h after cessation of exposure to filtered room air or O, we assessed lung inflammation and airway responsiveness in wild-type and IL-11Rα1-deficient mice. With the exception of bronchoalveolar lavage macrophages and adiponectin, which were significantly increased and decreased, respectively, in O-exposed IL-11Rα1-deficient as compared with O-exposed wild-type mice, no other genotype-related differences in lung inflammation indices that we quantified were observed in O-exposed mice. However, airway responsiveness to acetyl-β-methylcholine chloride (methacholine) was significantly diminished in IL-11Rα1-deficient as compared with wild-type mice after O exposure. In conclusion, these results demonstrate that IL-11Rα1 minimally contributes to lung inflammation but is required for maximal airway responsiveness to methacholine in a mouse model of nonatopic asthma.
白细胞介素（IL）-11 是一种多功能细胞因子，参与多种生物学过程，包括脂肪生成、造血和炎症。哮喘是一种呼吸系统疾病，其特征明显为可逆性气道阻塞、持续性肺部炎症和气道高反应性（AHR）。白细胞介素-11（IL-11）在野生型小鼠中的鼻腔内注射会导致 AHR，而抗原致敏和激发引起的肺部炎症，模拟了人类特应性哮喘的特征，在缺乏 IL-11 受体亚基 α-1（IL-11Rα1 缺陷型小鼠）的小鼠中减弱，IL-11Rα1 是一种跨膜受体，与糖蛋白 130共同需要转导 IL-11 信号。然而，IL-11Rα1 对非特应性哮喘特征的贡献尚不清楚。因此，基于上述观察结果，我们假设 IL-11Rα1 的遗传缺陷会减弱急性吸入臭氧（O）暴露后肺部炎症和气道反应性，O 是一种标准污染物和非特应性哮喘刺激物。因此，在停止暴露于过滤室空气或 O 4 和/或 24 小时后，我们评估了野生型和 IL-11Rα1 缺陷型小鼠的肺部炎症和气道反应性。除了支气管肺泡灌洗液中的巨噬细胞和脂联素分别显著增加和减少外，在 O 暴露的 IL-11Rα1 缺陷型小鼠中与 O 暴露的野生型小鼠相比，我们定量的肺部炎症指数没有观察到其他基因型相关差异。然而，与野生型小鼠相比，在 O 暴露后，IL-11Rα1 缺陷型小鼠对乙酰-β-甲基胆碱氯化物（乙酰胆碱）的气道反应性明显减弱。总之，这些结果表明，IL-11Rα1 对肺部炎症的贡献最小，但在非特应性哮喘小鼠模型中对乙酰胆碱的最大气道反应性是必需的。
