Cargando…
The Anti-inflammatory Effect of Soluble Epoxide Hydrolase Inhibitor and 14, 15-EET in Kawasaki Disease Through PPARγ/STAT1 Signaling Pathway
Soluble epoxide hydrolase (sEH) is responsible for rapid degradation of 14, 15-EET, which is one of the isomers of EETs and plays an important role in cardiovascular diseases. In this study, we investigated the mechanism by which sEH inhibitor AUDA played an anti-inflammatory effect in HCAECs. Our r...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434939/ https://www.ncbi.nlm.nih.gov/pubmed/32903307 http://dx.doi.org/10.3389/fped.2020.00451 |
_version_ | 1783572243385679872 |
---|---|
author | Dai, Na Yang, Chunyan Fan, Qing Wang, Minmin Liu, Xiaoyue Zhao, Haizhao Zhao, Cuifen |
author_facet | Dai, Na Yang, Chunyan Fan, Qing Wang, Minmin Liu, Xiaoyue Zhao, Haizhao Zhao, Cuifen |
author_sort | Dai, Na |
collection | PubMed |
description | Soluble epoxide hydrolase (sEH) is responsible for rapid degradation of 14, 15-EET, which is one of the isomers of EETs and plays an important role in cardiovascular diseases. In this study, we investigated the mechanism by which sEH inhibitor AUDA played an anti-inflammatory effect in HCAECs. Our results indicated that AUDA treatment promoted PPARγ expression, while knockdown of PPARγ blocked the cell growth and STAT1 expression inhibition induced by 100 μmol/L AUDA in HCAECs. AUDA also inhibited the overexpression of TNF-α, IL-1 β, and MMP-9 induced by KD sera in HCAECs. Moreover, 30 blood samples from children with Kawasaki disease (KD) were collected with 30 healthy children as the control group. QPCR and ELISA assays were used to detect the level of 14, 15-EET, TNF-α, IL-1β, and MMP-9. We found that the level of 14, 15-EET was higher in peripheral blood of children with KD compared with healthy controls (P < 0.05). In comparison to KD children with non-coronary artery lesion (nCAL), the level of 14, 15-EET was higher in peripheral blood of KD children with coronary artery lesion (CAL) (P < 0.05). Compared with healthy control group, the expression levels of TNF-α, IL-1β, and MMP-9 in patients with KD were significantly up-regulated. Compared with nCAL KD children, the expression levels of TNF-α, IL-1β, and MMP-9 in CAL children were abnormally high (P < 0.05). Our study indicated that AUDA played an anti-inflammatory effect in HCAECs through PPARγ/STAT1 signaling pathway, and 14, 15-EET is up-regulated in children with KD, suggesting that 14, 15-EET involved in the progression of KD. |
format | Online Article Text |
id | pubmed-7434939 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74349392020-09-03 The Anti-inflammatory Effect of Soluble Epoxide Hydrolase Inhibitor and 14, 15-EET in Kawasaki Disease Through PPARγ/STAT1 Signaling Pathway Dai, Na Yang, Chunyan Fan, Qing Wang, Minmin Liu, Xiaoyue Zhao, Haizhao Zhao, Cuifen Front Pediatr Pediatrics Soluble epoxide hydrolase (sEH) is responsible for rapid degradation of 14, 15-EET, which is one of the isomers of EETs and plays an important role in cardiovascular diseases. In this study, we investigated the mechanism by which sEH inhibitor AUDA played an anti-inflammatory effect in HCAECs. Our results indicated that AUDA treatment promoted PPARγ expression, while knockdown of PPARγ blocked the cell growth and STAT1 expression inhibition induced by 100 μmol/L AUDA in HCAECs. AUDA also inhibited the overexpression of TNF-α, IL-1 β, and MMP-9 induced by KD sera in HCAECs. Moreover, 30 blood samples from children with Kawasaki disease (KD) were collected with 30 healthy children as the control group. QPCR and ELISA assays were used to detect the level of 14, 15-EET, TNF-α, IL-1β, and MMP-9. We found that the level of 14, 15-EET was higher in peripheral blood of children with KD compared with healthy controls (P < 0.05). In comparison to KD children with non-coronary artery lesion (nCAL), the level of 14, 15-EET was higher in peripheral blood of KD children with coronary artery lesion (CAL) (P < 0.05). Compared with healthy control group, the expression levels of TNF-α, IL-1β, and MMP-9 in patients with KD were significantly up-regulated. Compared with nCAL KD children, the expression levels of TNF-α, IL-1β, and MMP-9 in CAL children were abnormally high (P < 0.05). Our study indicated that AUDA played an anti-inflammatory effect in HCAECs through PPARγ/STAT1 signaling pathway, and 14, 15-EET is up-regulated in children with KD, suggesting that 14, 15-EET involved in the progression of KD. Frontiers Media S.A. 2020-08-12 /pmc/articles/PMC7434939/ /pubmed/32903307 http://dx.doi.org/10.3389/fped.2020.00451 Text en Copyright © 2020 Dai, Yang, Fan, Wang, Liu, Zhao and Zhao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pediatrics Dai, Na Yang, Chunyan Fan, Qing Wang, Minmin Liu, Xiaoyue Zhao, Haizhao Zhao, Cuifen The Anti-inflammatory Effect of Soluble Epoxide Hydrolase Inhibitor and 14, 15-EET in Kawasaki Disease Through PPARγ/STAT1 Signaling Pathway |
title | The Anti-inflammatory Effect of Soluble Epoxide Hydrolase Inhibitor and 14, 15-EET in Kawasaki Disease Through PPARγ/STAT1 Signaling Pathway |
title_full | The Anti-inflammatory Effect of Soluble Epoxide Hydrolase Inhibitor and 14, 15-EET in Kawasaki Disease Through PPARγ/STAT1 Signaling Pathway |
title_fullStr | The Anti-inflammatory Effect of Soluble Epoxide Hydrolase Inhibitor and 14, 15-EET in Kawasaki Disease Through PPARγ/STAT1 Signaling Pathway |
title_full_unstemmed | The Anti-inflammatory Effect of Soluble Epoxide Hydrolase Inhibitor and 14, 15-EET in Kawasaki Disease Through PPARγ/STAT1 Signaling Pathway |
title_short | The Anti-inflammatory Effect of Soluble Epoxide Hydrolase Inhibitor and 14, 15-EET in Kawasaki Disease Through PPARγ/STAT1 Signaling Pathway |
title_sort | anti-inflammatory effect of soluble epoxide hydrolase inhibitor and 14, 15-eet in kawasaki disease through pparγ/stat1 signaling pathway |
topic | Pediatrics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434939/ https://www.ncbi.nlm.nih.gov/pubmed/32903307 http://dx.doi.org/10.3389/fped.2020.00451 |
work_keys_str_mv | AT daina theantiinflammatoryeffectofsolubleepoxidehydrolaseinhibitorand1415eetinkawasakidiseasethroughppargstat1signalingpathway AT yangchunyan theantiinflammatoryeffectofsolubleepoxidehydrolaseinhibitorand1415eetinkawasakidiseasethroughppargstat1signalingpathway AT fanqing theantiinflammatoryeffectofsolubleepoxidehydrolaseinhibitorand1415eetinkawasakidiseasethroughppargstat1signalingpathway AT wangminmin theantiinflammatoryeffectofsolubleepoxidehydrolaseinhibitorand1415eetinkawasakidiseasethroughppargstat1signalingpathway AT liuxiaoyue theantiinflammatoryeffectofsolubleepoxidehydrolaseinhibitorand1415eetinkawasakidiseasethroughppargstat1signalingpathway AT zhaohaizhao theantiinflammatoryeffectofsolubleepoxidehydrolaseinhibitorand1415eetinkawasakidiseasethroughppargstat1signalingpathway AT zhaocuifen theantiinflammatoryeffectofsolubleepoxidehydrolaseinhibitorand1415eetinkawasakidiseasethroughppargstat1signalingpathway AT daina antiinflammatoryeffectofsolubleepoxidehydrolaseinhibitorand1415eetinkawasakidiseasethroughppargstat1signalingpathway AT yangchunyan antiinflammatoryeffectofsolubleepoxidehydrolaseinhibitorand1415eetinkawasakidiseasethroughppargstat1signalingpathway AT fanqing antiinflammatoryeffectofsolubleepoxidehydrolaseinhibitorand1415eetinkawasakidiseasethroughppargstat1signalingpathway AT wangminmin antiinflammatoryeffectofsolubleepoxidehydrolaseinhibitorand1415eetinkawasakidiseasethroughppargstat1signalingpathway AT liuxiaoyue antiinflammatoryeffectofsolubleepoxidehydrolaseinhibitorand1415eetinkawasakidiseasethroughppargstat1signalingpathway AT zhaohaizhao antiinflammatoryeffectofsolubleepoxidehydrolaseinhibitorand1415eetinkawasakidiseasethroughppargstat1signalingpathway AT zhaocuifen antiinflammatoryeffectofsolubleepoxidehydrolaseinhibitorand1415eetinkawasakidiseasethroughppargstat1signalingpathway |