PMID- 31008484
OWN - NLM
STAT- MEDLINE
DCOM- 20190813
LR  - 20190813
IS  - 0371-0874 (Print)
IS  - 0371-0874 (Linking)
VI  - 71
IP  - 2
DP  - 2019 Apr 25
TI  - Prostaglandin E(2) receptors differentially regulate the output of 
      proinflammatory cytokines in myometrial cells from term pregnant women.
PG  - 248-260
AB  - Prostaglandin (PG) E(2) plays critical roles during pregnancy and parturition. 
      Emerging evidence indicates that human labour is an inflammatory event. We sought 
      to investigate the effect of PGE(2) on the output of proinflammatory cytokines in 
      cultured human uterine smooth muscle cells (HUSMCs) from term pregnant women and 
      elucidate the role of subtypes of PGE(2) receptors (EP(1), EP(2), EP(3) and 
      EP(4)). After drug treatment and/or transfection of each receptor siRNA, the 
      concentrations of inflammatory secreting factors in HUSMCs culture medium were 
      detected by the corresponding ELISA kits. The results showed that, PGE(2) 
      increased interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFalpha) output, 
      decreased chemokine (c-x-c motif) ligand 8 (CXCL8) output in a dose-dependent 
      manner, but had no effect on IL-1beta and chemokine (c-c motif) ligand 2 (CCL-2) 
      secretion of HUSMCs. EP(1)/EP(3) agonist 17-phenyl-trinor-PGE(2) stimulated IL-6 
      and TNFalpha whilst suppressing IL-1beta and CXCL8 output. The effects of 
      17-phenyl-trinor-PGE(2) on IL-1beta and CXCL8 secretion were remained whereas its 
      effect on IL-6 and TNFalpha output did not occur in the cells with EP(3) knockdown. 
      The stimulatory effects of 17-phenyl-trinor-PGE(2) on IL-6 and TNFalpha were remained 
      whereas the inhibitory effects of 17-phenyl-trinor-PGE(2) on IL-1beta secretion was 
      blocked in the cells with EP(1) knockdown. Either of EP(2) and EP(4) agonists 
      stimulated IL-1beta and TNFalpha output, which was reversed by EP(2) and EP(4) siRNA, 
      respectively. The inhibitors of phospholipase C (PLC) and protein kinase C (PKC) 
      blocked EP(1)/EP(3) modulation of TNFalpha and CXCL8 output. PI3K inhibitor LY294002 
      and P38 inhibitor SB202190 blocked 17-phenyl-trinor-PGE(2)-induced IL-1beta and IL-6 
      output, respectively. The inhibitors of adenylyl cyclase and PKA prevented EP(2) 
      and EP(4) stimulation of IL-1beta and TNFalpha output, whereas PLC and PKC inhibitors 
      blocked EP(2)- and EP(4)-induced TNFalpha output but not IL-1beta output. Our data 
      suggest that PGE(2) receptors exhibit different effects on the output of various 
      cytokines in myometrium, which can subtly modulate the inflammatory 
      microenvironment in myometrium during pregnancy.
FAU - Zhang, You-Yi
AU  - Zhang YY
AD  - Department of Physiology, Navy Military Medical University (Second Military 
      Medical University), Shanghai 200433, China.
FAU - Liu, Wei-Na
AU  - Liu WN
AD  - Department of Physiology, Navy Military Medical University (Second Military 
      Medical University), Shanghai 200433, China.
AD  - Department of Gynecology, Chinese PLA 413th Hospital, Zhoushan 316000, China.
FAU - You, Xing-Ji
AU  - You XJ
AD  - Department of Physiology, Navy Military Medical University (Second Military 
      Medical University), Shanghai 200433, China.
FAU - Gu, Hang
AU  - Gu H
AD  - Department of Obstetrics and Gynecology, Changhai Hospital, Shanghai 200433, 
      China.
FAU - Xu, Chen
AU  - Xu C
AD  - Department of Physiology, Navy Military Medical University (Second Military 
      Medical University), Shanghai 200433, China.
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Fudan University, Shanghai 200032, China.
FAU - Ni, Xin
AU  - Ni X
AD  - Department of Physiology, Navy Military Medical University (Second Military 
      Medical University), Shanghai 200433, China.
AD  - Research Center of Molecular Metabolomics, Xiangya Hospital, Central Southern 
      University, Changsha 410008, China. nixin@smmu.edu.cn.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Sheng Li Xue Bao
JT  - Sheng li xue bao : [Acta physiologica Sinica]
JID - 20730130R
RN  - 0 (Chromones)
RN  - 0 (Cytokines)
RN  - 0 (Imidazoles)
RN  - 0 (Morpholines)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Prostaglandin E)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - PVX798P8GI (4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole)
MH  - Cells, Cultured
MH  - Chromones/pharmacology
MH  - Cytokines/*metabolism
MH  - Female
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Inflammation
MH  - Morpholines/pharmacology
MH  - Myocytes, Smooth Muscle/*cytology
MH  - Myometrium/*cytology
MH  - Phosphatidylinositol 3-Kinases
MH  - Pregnancy
MH  - Pyridines/pharmacology
MH  - Receptors, Prostaglandin E/*physiology
EDAT- 2019/04/23 06:00
MHDA- 2019/08/14 06:00
CRDT- 2019/04/23 06:00
PHST- 2019/04/23 06:00 [entrez]
PHST- 2019/04/23 06:00 [pubmed]
PHST- 2019/08/14 06:00 [medline]
PST - ppublish
SO  - Sheng Li Xue Bao. 2019 Apr 25;71(2):248-260.