Carbon monoxide releasing molecule-2 attenuates Pseudomonas aeruginosa-induced ROS-dependent ICAM-1 expression in human pulmonary alveolar epithelial cells
Journal
Redox Biology
Journal Volume
18
Pages
93-103
Date Issued
2018
Author(s)
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. ? 2018
SDGs
Other Subjects
carbon monoxide; carbon monoxide releasing molecule 2; cytosol receptor; immunoglobulin enhancer binding protein; intercellular adhesion molecule 1; interleukin 6; Janus kinase; mitogen activated protein kinase 1; mitogen activated protein kinase 3; mitogen activated protein kinase 9; prostaglandin E2; protein kinase C alpha; protein p42; protein p47; protein p50; reactive oxygen metabolite; reduced nicotinamide adenine dinucleotide phosphate; small interfering RNA; synaptotagmin I; toll like receptor 4; unclassified drug; antiinflammatory agent; intercellular adhesion molecule 1; interleukin 6; organometallic compound; reactive oxygen metabolite; tricarbonyldichlororuthenium (II) dimer; antiinflammatory activity; Article; cell activation; cell adhesion; controlled study; cytokine release; enzyme inhibition; human; human cell; intracellular transport; lung alveolus epithelium cell; molecular mechanics; mRNA expression level; nonhuman; priority journal; protein expression; Pseudomonas aeruginosa; signal transduction; transient transfection; animal; cell line; complication; drug effect; immunology; inflammation; Institute for Cancer Research mouse; lung alveolus epithelium cell; male; microbiology; Pseudomonas aeruginosa; Pseudomonas infection; Alveolar Epithelial Cells; Animals; Anti-Inflammatory Agents; Cell Adhesion; Cell Line; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Male; Mice, Inbred ICR; Organometallic Compounds; Pseudomonas aeruginosa; Pseudomonas Infections; Reactive Oxygen Species
Publisher
Elsevier B.V.
Type
journal article