Progestins Inhibit Interleukin-1β-Induced Matrix Metalloproteinase 1 and Interleukin 8 Expression via the Glucocorticoid Receptor in Primary Human Amnion Mesenchymal Cells
Preterm premature rupture of membranes is a leading cause of preterm births. Cytokine induced matrix metalloproteinase1 and interleukin 8 production from amnion mesenchymal cells may contribute to fetal membrane weakening and rupture. Progestins inhibit inflammation induced fetal membrane weakening...
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| Language: | English |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2020.00900/full |
| _version_ | 1828850507987288064 |
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| author | William Marinello Liping Feng Terrence K. Allen |
| author_facet | William Marinello Liping Feng Terrence K. Allen |
| author_sort | William Marinello |
| collection | DOAJ |
| description | Preterm premature rupture of membranes is a leading cause of preterm births. Cytokine induced matrix metalloproteinase1 and interleukin 8 production from amnion mesenchymal cells may contribute to fetal membrane weakening and rupture. Progestins inhibit inflammation induced fetal membrane weakening but their effect on the inflammatory response of amnion mesenchymal cells is unknown. This study was designed to determine the role of progesterone receptor membrane component 1 and the glucocorticoid receptor in mediating the effects of progestins on interleukin-1β induced matrix metalloproteinase 1 and interleukin-8 expression in human amnion mesenchymal cells. Primary amnion mesenchymal cells harvested from human fetal membranes were passaged once and treated with vehicle, progesterone or medroxyprogesterone acetate at 10–6 M for 1 h followed by stimulation with interleukin-1β at 1 ng/ml for 24 h. Medroxyprogesterone acetate but not progesterone inhibited interleukin-1β-induced interlukin-8 and matrix metalloproteinase 1 mRNA expression. In subsequent dose response studies, medroxyprogesterone acetate, but not progesterone, at doses of 10–6–10–8 M inhibited interleukin-1β induced interleukin-8 and matrix metalloproteinase 1 mRNA expression. We further demonstrated that inhibition of glucocorticoid receptor expression, but not progesterone receptor membrane component 1 knockdown with small interfering RNA transfection, resulted in a reversal in medroxyprogesterone acetate’s (10–7 M) inhibition of interleukin-1β- induced matrix metalloproteinase 1 mRNA expression and interleukin-8 mRNA expression and protein expression. Our findings demonstrate that medroxyprogesterone acetate exerts its anti-inflammatory effect primarily through the glucocorticoid receptor in human amnion mesenchymal cells. Modulation of glucocorticoid receptor signaling pathways maybe a useful therapeutic strategy for preventing inflammation induced fetal membrane weakening leading to preterm premature rupture of membranes. |
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| id | doaj.art-e308a7477e2c483983f824acc1e06e54 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-12T23:13:16Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-e308a7477e2c483983f824acc1e06e542022-12-22T00:08:32ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-07-011110.3389/fphys.2020.00900540742Progestins Inhibit Interleukin-1β-Induced Matrix Metalloproteinase 1 and Interleukin 8 Expression via the Glucocorticoid Receptor in Primary Human Amnion Mesenchymal CellsWilliam Marinello0Liping Feng1Terrence K. Allen2Department of Anesthesiology, Duke University Hospital, Durham, NC, United StatesDepartment of Obstetrics and Gynecology, Duke University Hospital, Durham, NC, United StatesDepartment of Anesthesiology, Duke University Hospital, Durham, NC, United StatesPreterm premature rupture of membranes is a leading cause of preterm births. Cytokine induced matrix metalloproteinase1 and interleukin 8 production from amnion mesenchymal cells may contribute to fetal membrane weakening and rupture. Progestins inhibit inflammation induced fetal membrane weakening but their effect on the inflammatory response of amnion mesenchymal cells is unknown. This study was designed to determine the role of progesterone receptor membrane component 1 and the glucocorticoid receptor in mediating the effects of progestins on interleukin-1β induced matrix metalloproteinase 1 and interleukin-8 expression in human amnion mesenchymal cells. Primary amnion mesenchymal cells harvested from human fetal membranes were passaged once and treated with vehicle, progesterone or medroxyprogesterone acetate at 10–6 M for 1 h followed by stimulation with interleukin-1β at 1 ng/ml for 24 h. Medroxyprogesterone acetate but not progesterone inhibited interleukin-1β-induced interlukin-8 and matrix metalloproteinase 1 mRNA expression. In subsequent dose response studies, medroxyprogesterone acetate, but not progesterone, at doses of 10–6–10–8 M inhibited interleukin-1β induced interleukin-8 and matrix metalloproteinase 1 mRNA expression. We further demonstrated that inhibition of glucocorticoid receptor expression, but not progesterone receptor membrane component 1 knockdown with small interfering RNA transfection, resulted in a reversal in medroxyprogesterone acetate’s (10–7 M) inhibition of interleukin-1β- induced matrix metalloproteinase 1 mRNA expression and interleukin-8 mRNA expression and protein expression. Our findings demonstrate that medroxyprogesterone acetate exerts its anti-inflammatory effect primarily through the glucocorticoid receptor in human amnion mesenchymal cells. Modulation of glucocorticoid receptor signaling pathways maybe a useful therapeutic strategy for preventing inflammation induced fetal membrane weakening leading to preterm premature rupture of membranes.https://www.frontiersin.org/article/10.3389/fphys.2020.00900/fullprogestinspreterm premature rupture of membranesglucocorticoid receptorprogesterone receptorinterleukin-1 betaInterleukin-8 |
| spellingShingle | William Marinello Liping Feng Terrence K. Allen Progestins Inhibit Interleukin-1β-Induced Matrix Metalloproteinase 1 and Interleukin 8 Expression via the Glucocorticoid Receptor in Primary Human Amnion Mesenchymal Cells Frontiers in Physiology progestins preterm premature rupture of membranes glucocorticoid receptor progesterone receptor interleukin-1 beta Interleukin-8 |
| title | Progestins Inhibit Interleukin-1β-Induced Matrix Metalloproteinase 1 and Interleukin 8 Expression via the Glucocorticoid Receptor in Primary Human Amnion Mesenchymal Cells |
| title_full | Progestins Inhibit Interleukin-1β-Induced Matrix Metalloproteinase 1 and Interleukin 8 Expression via the Glucocorticoid Receptor in Primary Human Amnion Mesenchymal Cells |
| title_fullStr | Progestins Inhibit Interleukin-1β-Induced Matrix Metalloproteinase 1 and Interleukin 8 Expression via the Glucocorticoid Receptor in Primary Human Amnion Mesenchymal Cells |
| title_full_unstemmed | Progestins Inhibit Interleukin-1β-Induced Matrix Metalloproteinase 1 and Interleukin 8 Expression via the Glucocorticoid Receptor in Primary Human Amnion Mesenchymal Cells |
| title_short | Progestins Inhibit Interleukin-1β-Induced Matrix Metalloproteinase 1 and Interleukin 8 Expression via the Glucocorticoid Receptor in Primary Human Amnion Mesenchymal Cells |
| title_sort | progestins inhibit interleukin 1β induced matrix metalloproteinase 1 and interleukin 8 expression via the glucocorticoid receptor in primary human amnion mesenchymal cells |
| topic | progestins preterm premature rupture of membranes glucocorticoid receptor progesterone receptor interleukin-1 beta Interleukin-8 |
| url | https://www.frontiersin.org/article/10.3389/fphys.2020.00900/full |
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