PMID- 31885501 OWN - NLM STAT- MEDLINE DCOM- 20200608 LR - 20200608 IS - 1466-1861 (Electronic) IS - 0962-9351 (Print) IS - 0962-9351 (Linking) VI - 2019 DP - 2019 TI - Increased Soluble Epoxide Hydrolase in Human Gestational Tissues from Pregnancies Complicated by Acute Chorioamnionitis. PG - 8687120 LID - 10.1155/2019/8687120 [doi] LID - 8687120 AB - Chorioamnionitis (CAM) is primarily a polymicrobial bacterial infection involving chorionic and amniotic membranes that is associated with increased risk of preterm delivery. Epoxyeicosatrienoic acids (EETs) are eicosanoids generated from arachidonic acid by cytochrome P450 enzymes and further metabolized mainly by soluble epoxide hydrolase (sEH) to produce dihydroxyeicosatrienoic acids (DHETs). As a consequence of this metabolism of EETs, sEH reportedly exacerbates several disease states; however, its role in CAM remains unclear. The objectives of this study were to (1) determine the localization of sEH and compare the changes it undergoes in the gestational tissues (placentas and fetal membranes) of women with normal-term pregnancies and those with pregnancies complicated by acute CAM; (2) study the effects of lipopolysaccharide (LPS) on the expression of sEH in the human gestational tissues; and (3) investigate the effect of 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a specific sEH inhibitor, on LPS-induced changes in 14,15-DHET and cytokines such as interleukin- (IL-) 1beta and IL-6 in human gestational tissues in vitro and in pregnant mice. We found that women with pregnancies complicated by acute CAM had higher levels of sEH mRNA and protein in fetal membranes and villous tissues compared to those in women with normal-term pregnancies without CAM. Furthermore, fetal membrane and villous explants treated with LPS had higher tissue levels of sEH mRNA and protein and 14,15-DHET than those present in the vehicle controls, while the administration of AUDA in the media attenuated the LPS-induced production of 14,15-DHET in tissue homogenates and IL-1beta and IL-6 in the media of explant cultures. Administration of AUDA also reduced the LPS-induced changes of 14,15-DHET, IL-1beta, and IL-6 in the placentas of pregnant mice. Together, these results suggest that sEH participates in the inflammatory changes in human gestational tissues in pregnancies complicated by acute CAM. CI - Copyright (c) 2019 Tai-Ho Hung et al. FAU - Hung, Tai-Ho AU - Hung TH AUID- ORCID: 0000-0003-2354-7060 AD - Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taiwan. AD - Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Chen, Szu-Fu AU - Chen SF AUID- ORCID: 0000-0002-8398-883X AD - Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, Taipei, Taiwan. FAU - Wu, Chun-Hu AU - Wu CH AD - Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan. FAU - Kao, Chuan-Chi AU - Kao CC AD - Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Taiwan. FAU - Wu, Chung-Pu AU - Wu CP AUID- ORCID: 0000-0002-2434-3361 AD - Graduate Institute of Biomedical Sciences, Department of Physiology and Pharmacology and Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan. LA - eng PT - Journal Article DEP - 20191205 PL - United States TA - Mediators Inflamm JT - Mediators of inflammation JID - 9209001 RN - 0 (14,15-dihydroxyeicosatrienoic acid) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - EC 3.3.2.- (Epoxide Hydrolases) RN - FC398RK06S (8,11,14-Eicosatrienoic Acid) SB - IM MH - 8,11,14-Eicosatrienoic Acid/analogs & derivatives/metabolism MH - Amnion/drug effects/metabolism MH - Chorioamnionitis/*enzymology/metabolism MH - Epoxide Hydrolases/genetics/*metabolism MH - Female MH - Humans MH - Interleukin-1beta/metabolism MH - Interleukin-6/metabolism MH - Lipopolysaccharides/pharmacology MH - Placenta/drug effects/metabolism MH - Pregnancy PMC - PMC6915158 COIS- All the authors declare that they have no conflicts of interest. EDAT- 2019/12/31 06:00 MHDA- 2020/06/09 06:00 PMCR- 2019/12/05 CRDT- 2019/12/31 06:00 PHST- 2019/07/03 00:00 [received] PHST- 2019/10/17 00:00 [revised] PHST- 2019/10/26 00:00 [accepted] PHST- 2019/12/31 06:00 [entrez] PHST- 2019/12/31 06:00 [pubmed] PHST- 2020/06/09 06:00 [medline] PHST- 2019/12/05 00:00 [pmc-release] AID - 10.1155/2019/8687120 [doi] PST - epublish SO - Mediators Inflamm. 2019 Dec 5;2019:8687120. doi: 10.1155/2019/8687120. eCollection 2019.