TY - JOUR
T1 - Carbon monoxide releasing molecule-2 attenuates Pseudomonas aeruginosa-induced ROS-dependent ICAM-1 expression in human pulmonary alveolar epithelial cells
AU - Lee, Chiang Wen
AU - Wu, Cheng Hsun
AU - Chiang, Yao Chang
AU - Chen, Yuh Lien
AU - Chang, Kuo Ting
AU - Chuang, Chu Chun
AU - Lee, I. Ta
PY - 2018/9/1
Y1 - 2018/9/1
N2 - 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 E 2 (PGE 2 )/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 p47 phox , 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 PGE 2 /IL-6/ICAM-1 expression and lung inflammatory responses by reducing the ROS generation and the inflammatory pathways.
AB - 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 E 2 (PGE 2 )/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 p47 phox , 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 PGE 2 /IL-6/ICAM-1 expression and lung inflammatory responses by reducing the ROS generation and the inflammatory pathways.
KW - Carbon monoxide
KW - Intercellular adhesion molecule-1
KW - Lung inflammation
KW - NADPH oxidase
KW - Pseudomonas aeruginosa
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U2 - 10.1016/j.redox.2018.07.001
DO - 10.1016/j.redox.2018.07.001
M3 - Article
C2 - 30007888
AN - SCOPUS:85049517790
SN - 2213-2317
VL - 18
SP - 93
EP - 103
JO - Redox Biology
JF - Redox Biology
ER -