| First Author | Michaudel C | Year | 2018 |
| Journal | Front Immunol | Volume | 9 |
| Pages | 916 | PubMed ID | 29867931 |
| Mgi Jnum | J:310914 | Mgi Id | MGI:6762652 |
| Doi | 10.3389/fimmu.2018.00916 | Citation | Michaudel C, et al. (2018) Interleukin-1alpha Mediates Ozone-Induced Myeloid Differentiation Factor-88-Dependent Epithelial Tissue Injury and Inflammation. Front Immunol 9:916 |
| abstractText | Air pollution associated with ozone exposure represents a major inducer of respiratory disease in man. In mice, a single ozone exposure causes lung injury with disruption of the respiratory barrier and inflammation. We investigated the role of interleukin-1 (IL-1)-associated cytokines upon a single ozone exposure (1 ppm for 1 h) using IL-1alpha-, IL-1beta-, and IL-18-deficient mice or an anti-IL-1alpha neutralizing antibody underlying the rapid epithelial cell death. Here, we demonstrate the release of the alarmin IL-1alpha after ozone exposure and that the acute respiratory barrier injury and inflammation and airway hyperreactivity are IL-1alpha-dependent. IL-1alpha signaling via IL-1R1 depends on the adaptor protein myeloid differentiation factor-88 (MyD88). Importantly, epithelial cell signaling is critical, since deletion of MyD88 in lung type I alveolar epithelial cells reduced ozone-induced inflammation. In addition, intratracheal injection of recombinant rmIL-1alpha in MyD88(acid) mice led to reduction of inflammation in comparison with wild type mice treated with rmIL-1alpha. Therefore, a major part of inflammation is mediated by IL-1alpha signaling in epithelial cells. In conclusion, the alarmin IL-1alpha released upon ozone-induced tissue damage and inflammation is mediated by MyD88 signaling in epithelial cells. Therefore, IL-1alpha may represent a therapeutic target to attenuate ozone-induced lung inflammation and hyperreactivity. |
