15-Deoxy-Delta-12,14-prostaglandin J2 modulates pro-labour and pro-inflammatory responses in human myocytes, vaginal and amnion epithelial cells
BackgroundPrematurity 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...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.983924/full |
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| author | Zahirrah BM. Rasheed Zahirrah BM. Rasheed Yun S. Lee Yun S. Lee Sung H. Kim Sung H. Kim Tg Teoh Tg Teoh Tg Teoh David A. MacIntyre David A. MacIntyre Phillip R. Bennett Phillip R. Bennett Lynne Sykes Lynne Sykes Lynne Sykes |
| author_facet | Zahirrah BM. Rasheed Zahirrah BM. Rasheed Yun S. Lee Yun S. Lee Sung H. Kim Sung H. Kim Tg Teoh Tg Teoh Tg Teoh David A. MacIntyre David A. MacIntyre Phillip R. Bennett Phillip R. Bennett Lynne Sykes Lynne Sykes Lynne Sykes |
| author_sort | Zahirrah BM. Rasheed |
| collection | DOAJ |
| description | BackgroundPrematurity 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).MethodsCells 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.Results15dPGJ2 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.ConclusionWe 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. |
| first_indexed | 2024-04-11T20:04:35Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-11T20:04:35Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-61546a994fa14fbc9d592c42200f63a02022-12-22T04:05:23ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-09-011310.3389/fendo.2022.98392498392415-Deoxy-Delta-12,14-prostaglandin J2 modulates pro-labour and pro-inflammatory responses in human myocytes, vaginal and amnion epithelial cellsZahirrah BM. Rasheed0Zahirrah BM. Rasheed1Yun S. Lee2Yun S. Lee3Sung H. Kim4Sung H. Kim5Tg Teoh6Tg Teoh7Tg Teoh8David A. MacIntyre9David A. MacIntyre10Phillip R. Bennett11Phillip R. Bennett12Lynne Sykes13Lynne Sykes14Lynne Sykes15Imperial College Parturition Research Group, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United KingdomUniversiti Kebangsaan Malaysia (UKM) Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, MalaysiaImperial College Parturition Research Group, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United KingdomMarch of Dimes European Preterm Birth Prematurity Research Centre, Imperial College London, London, United KingdomImperial College Parturition Research Group, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United KingdomMarch of Dimes European Preterm Birth Prematurity Research Centre, Imperial College London, London, United KingdomImperial College Parturition Research Group, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United KingdomMarch of Dimes European Preterm Birth Prematurity Research Centre, Imperial College London, London, United KingdomThe Parasol Foundation Centre for Women’s Health and Cancer Research, St Mary’s Hospital, Imperial College Healthcare National Health Service (NHS) Trust, London, United KingdomImperial College Parturition Research Group, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United KingdomMarch of Dimes European Preterm Birth Prematurity Research Centre, Imperial College London, London, United KingdomImperial College Parturition Research Group, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United KingdomMarch of Dimes European Preterm Birth Prematurity Research Centre, Imperial College London, London, United KingdomImperial College Parturition Research Group, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United KingdomMarch of Dimes European Preterm Birth Prematurity Research Centre, Imperial College London, London, United KingdomThe Parasol Foundation Centre for Women’s Health and Cancer Research, St Mary’s Hospital, Imperial College Healthcare National Health Service (NHS) Trust, London, United KingdomBackgroundPrematurity 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).MethodsCells 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.Results15dPGJ2 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.ConclusionWe 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.https://www.frontiersin.org/articles/10.3389/fendo.2022.983924/fullnuclear factor - kappa B (NF - κB)activator protein (AP)-1inflammationcytokinesprostaglandinspreterm labour (PTL) |
| spellingShingle | Zahirrah BM. Rasheed Zahirrah BM. Rasheed Yun S. Lee Yun S. Lee Sung H. Kim Sung H. Kim Tg Teoh Tg Teoh Tg Teoh David A. MacIntyre David A. MacIntyre Phillip R. Bennett Phillip R. Bennett Lynne Sykes Lynne Sykes Lynne Sykes 15-Deoxy-Delta-12,14-prostaglandin J2 modulates pro-labour and pro-inflammatory responses in human myocytes, vaginal and amnion epithelial cells Frontiers in Endocrinology nuclear factor - kappa B (NF - κB) activator protein (AP)-1 inflammation cytokines prostaglandins preterm labour (PTL) |
| title | 15-Deoxy-Delta-12,14-prostaglandin J2 modulates pro-labour and pro-inflammatory responses in human myocytes, vaginal and amnion epithelial cells |
| title_full | 15-Deoxy-Delta-12,14-prostaglandin J2 modulates pro-labour and pro-inflammatory responses in human myocytes, vaginal and amnion epithelial cells |
| title_fullStr | 15-Deoxy-Delta-12,14-prostaglandin J2 modulates pro-labour and pro-inflammatory responses in human myocytes, vaginal and amnion epithelial cells |
| title_full_unstemmed | 15-Deoxy-Delta-12,14-prostaglandin J2 modulates pro-labour and pro-inflammatory responses in human myocytes, vaginal and amnion epithelial cells |
| title_short | 15-Deoxy-Delta-12,14-prostaglandin J2 modulates pro-labour and pro-inflammatory responses in human myocytes, vaginal and amnion epithelial cells |
| title_sort | 15 deoxy delta 12 14 prostaglandin j2 modulates pro labour and pro inflammatory responses in human myocytes vaginal and amnion epithelial cells |
| topic | nuclear factor - kappa B (NF - κB) activator protein (AP)-1 inflammation cytokines prostaglandins preterm labour (PTL) |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.983924/full |
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