| First Author | Johnston RA | Year | 2022 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 323 |
| Issue | 6 | Pages | R921-R934 |
| PubMed ID | 36283092 | Mgi Jnum | J:340375 |
| Mgi Id | MGI:7439736 | Doi | 10.1152/ajpregu.00213.2022 |
| Citation | Johnston RA, et al. (2022) Interleukin-11 receptor subunit alpha-1 is required for maximal airway responsiveness to methacholine after acute exposure to ozone. Am J Physiol Regul Integr Comp Physiol 323(6):R921-R934 |
| abstractText | 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-11Ralpha1-deficient mice), a transmembrane receptor that is required conjointly with glycoprotein 130 to transduce IL-11 signaling. Nevertheless, the contribution of IL-11Ralpha1 to characteristics of nonatopic asthma is unknown. Thus, based on the aforementioned observations, we hypothesized that genetic deficiency of IL-11Ralpha1 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-11Ralpha1-deficient mice. With the exception of bronchoalveolar lavage macrophages and adiponectin, which were significantly increased and decreased, respectively, in O(3)-exposed IL-11Ralpha1-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-11Ralpha1-deficient as compared with wild-type mice after O(3) exposure. In conclusion, these results demonstrate that IL-11Ralpha1 minimally contributes to lung inflammation but is required for maximal airway responsiveness to methacholine in a mouse model of nonatopic asthma. |
