Carbon monoxide ameliorates lipopolysaccharide-induced acute lung injury via inhibition of alveolar macrophage pyroptosis.

Exp Anim

Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507, Zhengmin Road, Yangpu District, Shanghai 200433, P.R. China.

Published: February 2023

Carbon monoxide (CO) has been reported to exhibit a therapeutic effect in lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the precise mechanism by which CO confers protection against ALI remains unclear. Pyroptosis has been recently proposed to play an essential role in the initiation and progression of ALI. Thus, we investigated whether pyroptosis is involved in the protection of CO against ALI and its underlying mechanism. First, an LPS-induced ALI mouse model was established. To determine the role of pyroptosis, we evaluated histological changes and the expression levels of cleaved caspase-11, N-gasdermin D (GSDMD), and IL-1β in lung tissues, which are the indicators of pyroptosis. Inhalation of CO exhibited protective effects on LPS-induced ALI by decreasing TNF-α and IL-10 expression and ameliorating pathological changes in lung tissue. In vitro, CO significantly reduced the expression of cleaved caspase-11, N-GSDMD, IL-1β, and IL-18. In addition, it increased nuclear factor E2-related factor 2 (NRF-2) expression in a time-dependent manner in RAW 264.7 cells and decreased N-GSDMD expression. The expression of cleaved GSDMD and release of LDH were increased after treatment with a specific NRF-2 inhibitor, ML385, indicating that NRF-2 mediates the inhibition of pyroptosis by CO. Taken together, these results demonstrated that CO upregulated NRF-2 to inhibit pyroptosis and subsequently ameliorated LPS-induced ALI.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9978127PMC
http://dx.doi.org/10.1538/expanim.22-0023DOI Listing

Publication Analysis

Top Keywords

lps-induced ali
12
carbon monoxide
8
acute lung
8
lung injury
8
protection ali
8
cleaved caspase-11
8
expression cleaved
8
pyroptosis
7
ali
7
expression
6

Similar Publications

Intranasal delivery of macrophage cell membrane cloaked biomimetic drug-nanoparticle system attenuates acute lung injury.

J Tissue Eng

December 2024

The First Dongguan Affiliated Hospital, Research Center of Nano Technology and Application Engineering, Dongguan Innovation Institute, Guangdong Medical University, Dongguan, China.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), a life-threatening disease, is typically induced by uncontrolled inflammatory responses and excessive production of reactive oxygen species (ROS). Astaxanthin (Ast) is known for its powerful natural antioxidant properties, showcasing excellent antioxidant, anti-inflammatory, and immunomodulatory effects. However, its poor water solubility and bioavailability significantly limit its efficacy.

View Article and Find Full Text PDF

Isoliquiritigenin Exhibits Anti-Inflammatory Responses in Acute Lung Injury by Covalently Binding to the Myeloid Differentiation Protein-2 Domain.

Phytother Res

December 2024

Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan and Education Ministry of P.R. China, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan Province, China.

Acute lung injury (ALI), a systemic inflammatory response with high morbidity, lacks effective pharmacological therapies. Myeloid differentiation protein-2 (MD2) has emerged as a promising therapeutic target for ALI. Herein, we aimed to evaluate the ability of isoliquiritigenin (ISL), a natural flavonoid found in licorice as a novel MD2 inhibitor, to inhibit lipopolysaccharide (LPS)-induced ALI.

View Article and Find Full Text PDF

Anti-inflammatory effect of nestorone in a lipopolysaccharide-induced acute lung injury model through regulation of the TLR-4/Myd88/NF-κB signaling pathway.

Inflammopharmacology

December 2024

Department of Liver Surgery and Transplantation and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Progesterone plays a crucial and indispensable role in regulating immunity and attenuating inflammation. Nestorone (NES, segesterone acetate) is a steroidal progestin and a 19-norprogesterone derivative with no -CH group radical at the 6-position. Here, we showed that NES enhanced the viability of lipopolysaccharide (LPS)-stimulated THP-1 cell-derived macrophages, potently inhibiting both arms of the Toll-like receptor 4 (TLR-4) signaling cascade triggered by LPS, especially the TLR-4/MyD88/NF-κB pathway.

View Article and Find Full Text PDF

Treating acute lung injury through scavenging of cell-free DNA by cationic nanoparticles.

Mater Today Bio

December 2024

Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou510630, PR China.

Acute lung injury (ALI) and acute respiratory distress syndrome are life-threatening conditions induced by inflammatory responses, in which cell-free DNA (cfDNA) plays a pivotal role. This study investigated the therapeutic potential of biodegradable cationic nanoparticles (cNPs) in alleviating ALI. Using a mouse model of lipopolysaccharide-induced ALI, we examined the impact of intravenously administered cNPs.

View Article and Find Full Text PDF

Exacerbation of pulmonary fibrosis following acute lung injury via activin-A production by recruited alveolar macrophages.

J Thorac Dis

November 2024

Shanghai Key Laboratory of Lung Inflammation and Injury, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Acute respiratory distress syndrome (ARDS) is a complicated pathological cascade process of excessive pulmonary inflammation and alveolar epithelial cell apoptosis that results in respiratory dysfunction and failure. Some cases of ARDS can result in a more severe state of pulmonary fibrosis, referred to as postinjury lung fibrosis. The mortality and incidence rate of ARDS are high, particularly when it leads to continuing alveolar and interstitial fibrosis, which requires urgent treatment and appropriate management.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!