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Thrombin and interleukin-1beta regulate HOXA10 expression in human term decidual cells: implications for preterm labor.

Jennifer L Sarno·Frederick Schatz·Charles J Lockwood·S-T Joseph Huang·Hugh S Taylor
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Abstract

CONTEXT: Preterm delivery is commonly caused by intraamniotic infection with expression of proinflammatory cytokines (IL-1beta) or by abruption resulting in generation of decidual thrombin. Although human parturition is not preceded by overt progesterone withdrawal, progesterone resistance likely leads to labor. The uteri of Hoxa10(-/-) mice demonstrate progesterone resistance; several genes, including prostaglandin receptors, are inappropriately regulated in response to progesterone. OBJECTIVE: We hypothesized that IL-1beta or thrombin would decrease HOXA10 expression, contributing to the progestin-resistant environment. We analyzed expression of HOX genes and their regulation by IL-1beta or thrombin in decidual cells. DESIGN AND SETTING: We conducted an in vitro experiment at an academic medical center. INTERVENTION: Term decidual cells were treated with estradiol (E(2)) or E(2) plus medroxyprogesterone acetate followed by addition of thrombin or IL-1beta. MAIN OUTCOME MEASURE: HOX mRNA was evaluated by microarray and confirmed by quantitative RT-PCR. Protein expression was detected using immunohistochemistry and Western analysis. RESULTS: HOXA9, HOXA10, and HOXA11 were expressed in decidual cells and regulated by IL-1beta and thrombin. HOXA10 was further analyzed because of its association with progesterone responsiveness. After E(2) treatment, IL-1beta and thrombin decreased HOXA10 mRNA by 94 and 81%, respectively. After E(2) plus medroxyprogesterone acetate treatment, IL-1beta and thrombin resulted in an 86 and 72% decrease in HOXA10 mRNA, respectively. A similar decrease was noted in HOXA10 protein expression. CONCLUSION: The expression of HOXA10 protein at term indicates that it may have a role in maintaining decidual cell phenotype and pregnancy. The dramatic decrease of HOXA10 in response to IL-1beta or thrombin may contribute to progestin resistance in preterm labor, mimicking progesterone resistance seen in Hoxa10(-/-) mice.

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Cells, CulturedDeciduaFemaleGene Expression RegulationHomeobox A10 ProteinsHomeodomain ProteinsHumansInterleukin-1Obstetric Labor, PrematurePregnancyProgesteroneThrombinJournal ArticleResearch Support, N.I.H., Extramural

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Jennifer L Sarno, Frederick Schatz, Charles J Lockwood, S-T Joseph Huang, Hugh S Taylor. 2006-03-21. Thrombin and interleukin-1beta regulate HOXA10 expression in human term decidual cells: implications for preterm labor.. https://doi.org/10.1210/jc.2005-1807

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