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

Chiang Wen Lee, Cheng Hsun Wu, Yao Chang Chiang, Yuh Lien Chen, Kuo Ting Chang, Chu Chun Chuang, I. Ta Lee

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)93-103
Number of pages11
JournalRedox Biology
Volume18
DOIs
Publication statusPublished - Sep 1 2018
Externally publishedYes

Fingerprint

Alveolar Epithelial Cells
Intercellular Adhesion Molecule-1
Carbon Monoxide
Pseudomonas aeruginosa
Lung
Molecules
Toll-Like Receptor 4
Chemical activation
Prostaglandins E
Inflammation
Interleukin-6
Tissue
Pulmonary diseases
Epithelial Cells
NADPH Oxidase
Biomarkers
Small Interfering RNA
Pseudomonas Infections
Anti-Inflammatory Agents
Cystic Fibrosis

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry

Cite this

Carbon monoxide releasing molecule-2 attenuates Pseudomonas aeruginosa-induced ROS-dependent ICAM-1 expression in human pulmonary alveolar epithelial cells. / Lee, Chiang Wen; Wu, Cheng Hsun; Chiang, Yao Chang; Chen, Yuh Lien; Chang, Kuo Ting; Chuang, Chu Chun; Lee, I. Ta.

In: Redox Biology, Vol. 18, 01.09.2018, p. 93-103.

Research output: Contribution to journalArticle

Lee, Chiang Wen ; Wu, Cheng Hsun ; Chiang, Yao Chang ; Chen, Yuh Lien ; Chang, Kuo Ting ; Chuang, Chu Chun ; Lee, I. Ta. / Carbon monoxide releasing molecule-2 attenuates Pseudomonas aeruginosa-induced ROS-dependent ICAM-1 expression in human pulmonary alveolar epithelial cells. In: Redox Biology. 2018 ; Vol. 18. pp. 93-103.
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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.

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