miR-155 modulates cockroach allergen- and oxidative stress-induced cyclooxygenase-2 in asthma

Lipeng Qiu, Yan Zhang, Danh C. Do, Xia Ke, Simin Zhang, Kristin Lambert, Shruthi Kumar, Chengping Hu, Yufeng Zhou, Faoud T. Ishmael, Peisong Gao

Research output: Contribution to journalArticle

Abstract

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 RT2 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-1552/2 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-1552/2 mice also showed reduced lung inflammation and Th2/Th17 cytokines. In contrast, when miR-1552/2 mice were transfected with adeno-associated virus carrying miR-155, the phenotypic changes in CRE-treated miR-1552/2 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.

Original languageEnglish (US)
Pages (from-to)916-929
Number of pages14
JournalJournal of Immunology
Volume201
Issue number3
DOIs
StatePublished - Aug 1 2018

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Qiu, L., Zhang, Y., Do, D. C., Ke, X., Zhang, S., Lambert, K., Kumar, S., Hu, C., Zhou, Y., Ishmael, F. T., & Gao, P. (2018). miR-155 modulates cockroach allergen- and oxidative stress-induced cyclooxygenase-2 in asthma. Journal of Immunology, 201(3), 916-929. https://doi.org/10.4049/jimmunol.1701167