TY - JOUR
T1 - miR-155 modulates cockroach allergen- and oxidative stress-induced cyclooxygenase-2 in asthma
AU - Qiu, Lipeng
AU - Zhang, Yan
AU - Do, Danh C.
AU - Ke, Xia
AU - Zhang, Simin
AU - Lambert, Kristin
AU - Kumar, Shruthi
AU - Hu, Chengping
AU - Zhou, Yufeng
AU - Ishmael, Faoud T.
AU - Gao, Peisong
N1 - Funding Information:
This work was supported by grants from the U.S. National Institutes of Health (R01ES021739, R21 AI109062, and R21 AI121768) and the National Science Foundation of China (NSFC) (81628001) (to P.G.), the Doris Duke Charitable Foundation Clinician Scientist Development Award (to F.T.I.), and NSFC 81402840 and the National Science Foundation of Jiangsu Province, China (BK20130495) (to L.Q.). It was also supported by grants from the NSFC (81671561), the National Key R&D Program of China (2016YFC1305102), and
Funding Information:
This work was supported by grants from the U.S. National Institutes of Health (R01ES021739, R21 AI109062, and R21 AI121768) and the National Science Foundation of China (NSFC) (81628001) (to P.G.), the Doris Duke Charitable Foundation Clinician Scientist Development Award (to F.T.I.), and NSFC 81402840 and the National Science Foundation of Jiangsu Province, China (BK20130495) (to L.Q.). It was also supported by grants from the NSFC (81671561), the National Key R&D Program of China (2016YFC1305102), and the Shanghai Municipal Planning Commission of Science and Research Fund (201740065) (to Y. Zhou).
Publisher Copyright:
© 2018 American Association of Immunologists. All rights reserved.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1701167
DO - 10.4049/jimmunol.1701167
M3 - Article
C2 - 29967100
AN - SCOPUS:85050767643
SN - 0022-1767
VL - 201
SP - 916
EP - 929
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -