| First Author | Qiu L | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 3 | Pages | 916-929 |
| PubMed ID | 29967100 | Mgi Jnum | J:264319 |
| Mgi Id | MGI:6195449 | Doi | 10.4049/jimmunol.1701167 |
| Citation | Qiu L, et al. (2018) miR-155 Modulates Cockroach Allergen- and Oxidative Stress-Induced Cyclooxygenase-2 in Asthma. J Immunol 201(3):916-929 |
| abstractText | Exposure to cockroach allergen is a strong risk factor for developing asthma. Asthma has been associated with allergen-induced airway epithelial damage and heightened oxidant stress. In this study, we investigated cockroach allergen-induced oxidative stress in airway epithelium and its underlying mechanisms. We found that cockroach extract (CRE) could induce reactive oxygen species (ROS) production, particularly mitochondrial-derived ROS, in human bronchial epithelial cells. We then used the RT(2) Profiler PCR array and identified that cyclooxygenase-2 (COX-2) was the most significantly upregulated gene related to CRE-induced oxidative stress. miR-155, predicted to target COX-2, was increased in CRE-treated human bronchial epithelial cells, and was showed to regulate COX-2 expression. Moreover, miR-155 can bind COX-2, induce COX-2 reporter activity, and maintain mRNA stability. Furthermore, CRE-treated miR-155(-/-) mice showed reduced levels of ROS and COX-2 expression in lung tissues and PGE2 in bronchoalveolar lavage fluid compared with wild-type mice. These miR-155(-/-) mice also showed reduced lung inflammation and Th2/Th17 cytokines. In contrast, when miR-155(-/-) mice were transfected with adeno-associated virus carrying miR-155, the phenotypic changes in CRE-treated miR-155(-/-) mice were remarkably reversed, including ROS, COX-2 expression, lung inflammation, and Th2/Th17 cytokines. Importantly, plasma miR-155 levels were elevated in severe asthmatics when compared with nonasthmatics or mild-to-moderate asthmatics. These increased plasma miR-155 levels were also observed in asthmatics with cockroach allergy compared with those without cockroach allergy. Collectively, these findings suggest that COX-2 is a major gene related to cockroach allergen-induced oxidative stress and highlight a novel role of miR-155 in regulating the ROS-COX-2 axis in asthma. |
