c-Fos is a mechanosensor that regulates inflammatory responses and lung barrier dysfunction during ventilator-induced acute lung injury.

Abstract

BACKGROUND:

As one of the basic treatments performed in the intensive care unit, mechanical ventilation can cause ventilator-induced acute lung injury (VILI). The typical features of VILI are an uncontrolled inflammatory response and impaired lung barrier function; however, its pathogenesis is not fully understood, and c-Fos protein is activated under mechanical stress. c-Fos/activating protein-1 (AP-1) plays a role by binding to AP-1 within the promoter region, which promotes inflammation and apoptosis. T-5224 is a specific inhibitor of c-Fos/AP-1, that controls the gene expression of many proinflammatory cytokines. This study investigated whether T-5224 attenuates VILI in rats by inhibiting inflammation and apoptosis.

METHODS:

The SD rats were divided into six groups: a control group, low tidal volume group, high tidal volume group, DMSO group, T-5224 group (low concentration), and T-5224 group (high concentration). After 3 h, the pathological damage, c-Fos protein expression, inflammatory reaction and apoptosis degree of lung tissue in each group were detected.

RESULTS:

c-Fos protein expression was increased within the lung tissue of VILI rats, and the pathological damage degree, inflammatory reaction and apoptosis in the lung tissue of VILI rats were significantly increased; T-5224 inhibited c-Fos protein expression in lung tissues, and T-5224 inhibit the inflammatory reaction and apoptosis of lung tissue by regulating the Fas/Fasl pathway.

CONCLUSIONS:

c-Fos is a regulatory factor during ventilator-induced acute lung injury, and the inhibition of its expression has a protective effect. Which is associated with the antiinflammatory and antiapoptotic effects of T-5224.

• Authors: Leilei Zhou, Chunju Xue, Zongyu Chen, Wenqing Jiang, Shuang He, Xianming Zhang
• Journal: BMC pulmonary medicine (BMC Pulm Med) Vol. 22 Issue 1 Pg. 9 (Jan 06 2022) ISSN: 1471-2466 [Electronic] England
• PMID: 34986829 (Publication Type: Comparative Study, Journal Article)
• Copyright: © 2021. The Author(s).

Chemical References

• 3-(5-(4-(cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxy-1,2-benzisoxazol-6-yl)methoxy)phenyl)propionic acid
• Benzophenones
• Isoxazoles
• Proto-Oncogene Proteins c-fos

Topics

• Animals
• Apoptosis (drug effects)
• Benzophenones (pharmacology)
• Inflammation (pathology)
• Isoxazoles (pharmacology)
• Male
• Proto-Oncogene Proteins c-fos (metabolism, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Ventilator-Induced Lung Injury (drug therapy, physiopathology)