Soluble epoxide hydrolase deficiency attenuates airway inflammation in COPD via IRE1α/JNK/AP-1 signaling pathway

• Published in: Journal of inflammation (London, England) Vol. 20; no. 1; pp. 1 - 36
• Main Authors: Yu, Yue, Yang, Ailin, He, Xin, Wu, Bo, Wu, Yanjun, Li, Yunxiao, Nie, Shan, Xu, Bo, Wang, Haoyan, Yu, Ganggang
• Format: Journal Article
• Language: English
• Published: London BioMed Central 01-11-2023; BMC
• Subjects: Antibodies; Chronic obstructive pulmonary disease; Cigarette smoke; Cigarettes; COPD; Electron microscopes; Emphysema; Endoplasmic reticulum; Endoplasmic reticulum stress; Enzymes; Epithelial cells; Epoxide hydrolase; Fatty acids; Inflammation; Kinases; Lung diseases; Lungs; Obstructive lung disease; Phosphorylation; Physiology; Proteins; Respiratory system; Respiratory tract diseases; Secretion; Signal transduction; Soluble epoxide hydrolase; Staphylococcal enterotoxin H; Transcription factors; Beijing China; United States > US; China
• ISSN: 1476-9255; 1476-9255
• DOI: 10.1186/s12950-023-00361-y

Abstract
Background
Soluble Epoxide Hydrolase (sEH) metabolizes anti-inflammatory epoxyeicosatrienoic acids and critically affects airway inflammation in chronic obstructive pulmonary disease (COPD). Considering the excessive endoplasmic reticulum stress is associated with the earlier onset of COPD. The role of sEH and endoplasmic reticulum stress in the pathogenesis of COPD remains unknown.
Method
16 weeks of cigarette-exposed mice were used to detect the relationship between sEH and endoplasmic reticulum stress in COPD. Human epithelial cells were used in vitro to determine the regulation mechanism of sEH in endoplasmic reticulum stress induced by cigarette smoke.
Results
sEH deficiency helps reduce emphysema formation after smoke exposure by alleviating endoplasmic reticulum stress response. sEH deficiency effectively reverses the upregulation of phosphorylation IRE1α and JNK and the nuclear expression of AP-1, alleviating the secretion of inflammatory factors induced by cigarette smoke extract. Furthermore, the treatment with endoplasmic reticulum stress and IRE1α inhibitor downregulated cigarette smoke extract-induced sEH expression and the secretion of inflammatory factors.
Conclusion
sEH probably alleviates airway inflammatory response and endoplasmic reticulum stress via the IRE1α/JNK/AP-1 pathway, which might attenuate lung injury caused by long-term smoking and provide a new pharmacological target for preventing and treating COPD.