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

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Title: 15-Deoxy-Delta-12,14-prostaglandin J2 modulates pro-labour and pro-inflammatory responses in human myocytes, vaginal and amnion epithelial cells
Authors: Rasheed, Z
Lee, Y
Kim, S
Teoh, TG
MacIntyre, D
Bennett, P
Sykes, L
Item Type: Journal Article
Abstract: 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-κB 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 32μM of 15dPGJ2 and stimulated with 1ng/mL of IL-1β as an in vitro model of inflammation. Western immunoblotting was used to detect phosphorylated p-65 and phosphorylated c-Jun as markers of NF-κB and AP-1 activation, respectively. mRNA expression of the pro-inflammatory cytokines IL-6, IL-8, and TNF-α 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-1β-induced activation of NF-κB and AP-1, and expression of IL-6, IL-8, TNF-α, COX-2 and PGE2 in myocytes, with no effect on myometrial contractility or cell viability. Despite inhibiting IL-1β-induced activation of NF-κB, expression of IL-6, TNF-α, 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.
Issue Date: 21-Sep-2022
Date of Acceptance: 31-Aug-2022
URI: http://hdl.handle.net/10044/1/99562
DOI: 10.3389/fendo.2022.983924
ISSN: 1664-2392
Publisher: Frontiers Media
Journal / Book Title: Frontiers in Endocrinology
Volume: 13
Copyright Statement: © 2022 Rasheed, Lee, Kim, Teoh, MacIntyre, Bennett and Sykes. 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.
Sponsor/Funder: Majlis Amanah Rakyat (MARA), Malaysian Government Agency
Wellbeing of Women
Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: MR/L009226/1
MR/L009226/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
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
15dPGJ2
activator protein (AP)-1
cytokines
inflammation
nuclear factor - kappa B (NF - κB)
preterm labour (PTL)
prostaglandins
Amnion
Animals
Anti-Inflammatory Agents
Cyclooxygenase 2
Cytokines
Dinoprostone
Epithelial Cells
Female
Humans
Infant, Newborn
Inflammation
Interleukin-6
Interleukin-8
Lipopolysaccharides
Mice
Muscle Cells
NF-kappa B
Premature Birth
Prostaglandin D2
RNA, Messenger
Transcription Factor AP-1
Tumor Necrosis Factor-alpha
Amnion
Epithelial Cells
Muscle Cells
Animals
Humans
Mice
Premature Birth
Inflammation
Lipopolysaccharides
Prostaglandin D2
Dinoprostone
Tumor Necrosis Factor-alpha
NF-kappa B
Transcription Factor AP-1
RNA, Messenger
Anti-Inflammatory Agents
Interleukin-8
Interleukin-6
Cytokines
Infant, Newborn
Female
Cyclooxygenase 2
1103 Clinical Sciences
1111 Nutrition and Dietetics
Publication Status: Published
Article Number: 983924
Online Publication Date: 2022-09-21
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Faculty of Medicine



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