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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 |
This item is licensed under a Creative Commons License