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

Redox Biology
Chiang-Wen LeeI-Ta Lee

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 ...Continue Reading

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Citations

Nov 21, 2018·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Hui LiuWei Lu
Jul 25, 2019·Frontiers in Cellular and Infection Microbiology·Lili WangZhigang Huang
Aug 5, 2021·Dementia & Neuropsychologia·Emille Magalhães Neves CamposJúlio César Claudino Dos Santos

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Methods Mentioned

BETA
protein assay
transfection
PCR
ELISA

Software Mentioned

GraphPad Prism
GraphPad

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