15-Deoxy-Delta-12,14-prostaglandin J2 modulates pro-labour and pro-inflammatory responses in human myocytes, vaginal and amnion epithelial cells

被引:2
作者
Rasheed, Zahirrah BM. [1 ,2 ]
Lee, Yun S. S. [1 ,3 ]
Kim, Sung H. H. [1 ,3 ]
Teoh, Tg [1 ,3 ,4 ]
MacIntyre, David A. A. [1 ,3 ]
Bennett, Phillip R. R. [1 ,3 ]
Sykes, Lynne [1 ,3 ,4 ]
机构
[1] Imperial Coll London, Imperial Coll, Dept Metab Digest & Reprod, Parturit Res Grp, London, England
[2] Univ Kebangsaan Malaysia UKM, Med Mol Biol Inst UMBI, Kuala Lumpur, Malaysia
[3] Imperial Coll London, March Dimes European Preterm Birth Prematur Res Ct, London, England
[4] St Marys Hosp, Parasol Fdn Ctr Womens Hlth & Canc Res, Imperial Coll Healthcare Natl Hlth Serv NHS Trust, London, England
来源
FRONTIERS IN ENDOCRINOLOGY | 2022年 / 13卷
基金
英国医学研究理事会;
关键词
nuclear factor- kappa B (NF-kB); activator protein (AP)-1; inflammation; cytokines; prostaglandins; preterm labour (PTL); 15dPGJ2; ACTIVATED RECEPTOR-GAMMA; HUMAN GESTATIONAL TISSUES; FACTOR-KAPPA-B; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); PRETERM LABOR; 15-HYDROXYPROSTAGLANDIN DEHYDROGENASE; CYCLOOXYGENASE-2; EXPRESSION; PROINFLAMMATORY CYTOKINES; DIFFERENTIAL EXPRESSION; INTRAUTERINE INFECTION;
D O I
10.3389/fendo.2022.983924
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Prematurity is the leading cause of childhood death under the age of five. The aetiology of preterm birth is multifactorial; however, inflammation and infection are the most common causal factors, supporting a potential role for immunomodulation as a therapeutic strategy. 15-Deoxy-Delta-12,14-prostaglandin J2 (15dPGJ2) is an anti-inflammatory prostaglandin and has been shown to delay lipopolysaccharide (LPS) induced preterm labour in mice and improve pup survival. This study explores the immunomodulatory effect of 15dPGJ2 on the transcription factors NF-kappa B and AP-1, pro-inflammatory cytokines, and contraction associated proteins in human cultured myocytes, vaginal epithelial cell line (VECs) and primary amnion epithelial cells (AECs). Methods: Cells were pre-incubated with 32 mu M of 15dPGJ2 and stimulated with 1ng/mL of IL-1 beta as an in vitro model of inflammation. Western immunoblotting was used to detect phosphorylated p-65 and phosphorylated c-Jun as markers of NF-kappa B and AP-1 activation, respectively. mRNA expression of the pro-inflammatory cytokines IL-6, IL-8, and TNF-alpha was examined, and protein expression of COX-2 and PGE2 were detected by western immunoblotting and ELISA respectively. Myometrial contractility was examined ex-vivo using a myograph. Results: 15dPGJ2 inhibited IL-1 beta-induced activation of NF-kappa B and AP-1, and expression of IL-6, IL-8, TNF-alpha, COX-2 and PGE2 in myocytes, with no effect on myometrial contractility or cell viability. Despite inhibiting IL-1 beta-induced activation of NF-kappa B, expression of IL-6, TNF-alpha, and COX-2, 15dPGJ2 led to activation of AP-1, increased production of PGE2 and increased cell death in VECs and AECs. Conclusion: We conclude that 15dPGJ2 has differential effects on inflammatory modulation depending on cell type and is therefore unlikely to be a useful therapeutic agent for the prevention of preterm birth.
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页数:18
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