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Redox Biol. 2018 Sep;18:93-103. doi: 10.1016/j.redox.2018.07.001. Epub 2018 Jul 4.

Carbon monoxide releasing molecule-2 attenuates Pseudomonas aeruginosa-induced ROS-dependent ICAM-1 expression in human pulmonary alveolar epithelial cells.

Author information

1
Division of Basic Medical Sciences, Department of Nursing and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chiayi, Taiwan, ROC; Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan, Taiwan, ROC; Department of Rehabilitation, Chang Gung Memorial Hospital, Chia-Yi, Taiwan, ROC.
2
School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan, ROC.
3
Division of Basic Medical Sciences, Department of Nursing and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chiayi, Taiwan, ROC; Center for Drug Abuse and Addiction, China Medical University Hospital, China Medical University, Taichung, Taiwan, ROC.
4
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
5
Translational Medicine Center, Taoyuan General Hospital, Ministry of Healthy and Welfare, Taoyuan, Taiwan, ROC.
6
Department of Physical Therapy, China Medical University, Taichung, Taiwan, ROC.
7
Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC; Department of Nursing, College of Nursing, Hungkuang University, Taichung, Taiwan, ROC. Electronic address: itl700128@gmail.com.

Abstract

Pseudomonas aeruginosa (P. aeruginosa) infection in the lung is common in patients with cystic fibrosis (CF). Intercellular adhesion molecule-1 (ICAM-1) is known to play a key role in lung inflammation. Acute inflammation and its timely resolution are important to ensure bacterial clearance and limit tissue damage. Carbon monoxide (CO) has been shown to exert anti-inflammatory effects in various tissues and organ systems. Here, we explored the protective effects and mechanisms of carbon monoxide releasing molecule-2 (CORM-2) on P. aeruginosa-induced inflammatory responses in human pulmonary alveolar epithelial cells (HPAEpiCs). We showed that P. aeruginosa induced prostaglandin E2 (PGE2)/interleukin-6 (IL-6)/ICAM-1 expression and monocyte adherence to HPAEpiCs. Moreover, P. aeruginosa-induced inflammatory responses were inhibited by transfection with siRNA of Toll-like receptor 4 (TLR4), PKCα, p47phox, JNK2, p42, p50, or p65. P. aeruginosa also induced PKCα, JNK, ERK1/2, and NF-κB activation. We further demonstrated that P. aeruginosa increased intracellular ROS generation via NADPH oxidase activation. On the other hand, P. aeruginosa-induced inflammation was inhibited by pretreatment with CORM-2. Preincubation with CORM-2 had no effects on TLR4 mRNA levels in response to P. aeruginosa. However, CORM-2 inhibits P. aeruginosa-induced inflammation by decreasing intracellular ROS generation. P. aeruginosa-induced PKCα, JNK, ERK1/2, and NF-κB activation was inhibited by CORM-2. Finally, we showed that P. aeruginosa induced levels of the biomarkers of inflammation in respiratory diseases, which were inhibited by pretreatment with CORM-2. Taken together, these data suggest that CORM-2 inhibits P. aeruginosa-induced PGE2/IL-6/ICAM-1 expression and lung inflammatory responses by reducing the ROS generation and the inflammatory pathways.

KEYWORDS:

Carbon monoxide; Intercellular adhesion molecule-1; Lung inflammation; NADPH oxidase; Pseudomonas aeruginosa

PMID:
30007888
PMCID:
PMC6039312
DOI:
10.1016/j.redox.2018.07.001
[Indexed for MEDLINE]
Free PMC Article

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