Title : Inhibition of soluble epoxide hydrolase attenuates airway remodeling in a chronic asthma model - Jiang_2020_Eur.J.Pharmacol_868_172874 |
Author(s) : Jiang JX , Guan Y , Shen HJ , Jia YL , Shen J , Zhang LH , Liu Q , Zhu YL , Xie QM |
Ref : European Journal of Pharmacology , 868 :172874 , 2020 |
Abstract :
Airway remodeling in asthma is difficult to treat because of its complex pathophysiology that involves proinflammatory cytokines, as well as the arachidonic acid cytochrome P-450 (CYP) pathway; however, it has received little attention. In this study, we assessed the efficacy of a soluble epoxide hydrolase (sEH) on airway remodeling in a mouse model of chronic asthma. The expression of sEH and CYP2J2 and the level of 14,15-epoxyeicosatrienoic acid (14,15-EET), airway remodeling and hyperresponsiveness (AHR) were analyzed to determine the level of sEH inhibition. AUDA, a sEH inhibitor, was given daily for 9 weeks orally, which significantly increased the level of 14,15-EET by inhibiting the expression of sEH and increasing the expression of CYP2J2 in lung tissues. The inhibition of sEH reduced the expression of remodeling-related molecular markers, such as interleukin (IL)-13, IL-17, matrix metalloproteinase 9, N-cadherin, alpha-smooth muscle actin (alpha-SMA), S100A4, Twist, epithelial goblet cell metaplasia, and collagen deposition in bronchoalveolar lavage fluid (BAL fluid) and lung tissues. Moreover, remodeling-related eosinophil accumulation in the BAL fluid and infiltration into the lung tissue were improved by AUDA. Finally, AUDA alleviated AHR, which is a functional indicator of airway remodeling. The effect of AUDA on airway remodeling was related to the downregulation of extracellular-regulated protein kinases (Erk1/2), c-Jun N-terminal kinases (JNK) and signal transducer and activator of transcription 3 (STAT3). To our knowledge, this is the first report to demonstrate that inhibition of sEH exerts significant protective effects on airway remodeling in asthma. |
PubMedSearch : Jiang_2020_Eur.J.Pharmacol_868_172874 |
PubMedID: 31866410 |
Jiang JX, Guan Y, Shen HJ, Jia YL, Shen J, Zhang LH, Liu Q, Zhu YL, Xie QM (2020)
Inhibition of soluble epoxide hydrolase attenuates airway remodeling in a chronic asthma model
European Journal of Pharmacology
868 :172874
Jiang JX, Guan Y, Shen HJ, Jia YL, Shen J, Zhang LH, Liu Q, Zhu YL, Xie QM (2020)
European Journal of Pharmacology
868 :172874