Fahad T. Alotaibi Ph.D. , Sadaf Sediqi B.Sc., Christian Klausen Ph.D., Mohamed A. Bedaiwy M.D., Ph.D., Paul J. Yong M.D., Ph.D.
{"title":"Interleukin-1β and plasminogen activating system members in endometriotic stromal cell migration/invasion","authors":"Fahad T. Alotaibi Ph.D. , Sadaf Sediqi B.Sc., Christian Klausen Ph.D., Mohamed A. Bedaiwy M.D., Ph.D., Paul J. Yong M.D., Ph.D.","doi":"10.1016/j.xfss.2022.09.004","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>To study the role of interleukin (IL)-1β and the plasminogen<span> activating (PA) system members in endometriotic stromal cell (ESC) migration/invasion.</span></p></div><div><h3>Design</h3><p>Primary cultures of ESCs.</p></div><div><h3>Setting</h3><p>Tertiary referral center for endometriosis<span> and pelvic pain.</span></p></div><div><h3>Patient(s)</h3><p>Patients with surgically excised endometriosis.</p></div><div><h3>Intervention(s)</h3><p>Interleukin-1β stimulation of primary cultures of ESCs and knockdown of the PA system members urokinase plasminogen activator<span> (uPA), uPA receptor, and plasminogen activator inhibitor-1 (PAI-1).</span></p></div><div><h3>Main Outcome Measure(s)</h3><p>Invasion/migration assays.</p></div><div><h3>Result(s)</h3><p>In primary cultures, IL-1β–stimulated ESC production of the PA system members uPA, uPA receptor, and PAI-1. Interleukin-1β also enhanced ESC migration and invasion, and these effects were inhibited by the IL-1 receptor-1 antagonist anakinra<span>. Knockdown of each of the 3 PA system members also inhibited ESC migration and invasion. Knockdown of these PA system members further attenuated the impact of IL-1β on migration and invasion, suggesting that they mediated the promigration and proinvasion effects of IL-1β. To supplement the cell culture work, immunohistochemistry was performed on tissue sections of endometriotic epithelium/stroma: uPA, PAI-1, and IL-1β histoscores were not found to be correlated with each other.</span></p></div><div><h3>Conclusion(s)</h3><p>In primary cultures of ESCs, IL-1β induces migration and invasion, which is mediated by PA system members and inhibited by the drug<span> anakinra. However, the immunohistochemistry expression of IL-1β, urokinase plasminogen inhibitor-1, and PAI-1 were not correlated, suggesting other regulatory mechanisms for PA system members. Inhibition of IL-1β (e.g., with anakinra) may have potential as a novel treatment approach for the migration/invasion of endometriosis.</span></p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 1","pages":"Pages 47-55"},"PeriodicalIF":0.0000,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"F&S science","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666335X22000623","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Objective
To study the role of interleukin (IL)-1β and the plasminogen activating (PA) system members in endometriotic stromal cell (ESC) migration/invasion.
Design
Primary cultures of ESCs.
Setting
Tertiary referral center for endometriosis and pelvic pain.
Patient(s)
Patients with surgically excised endometriosis.
Intervention(s)
Interleukin-1β stimulation of primary cultures of ESCs and knockdown of the PA system members urokinase plasminogen activator (uPA), uPA receptor, and plasminogen activator inhibitor-1 (PAI-1).
Main Outcome Measure(s)
Invasion/migration assays.
Result(s)
In primary cultures, IL-1β–stimulated ESC production of the PA system members uPA, uPA receptor, and PAI-1. Interleukin-1β also enhanced ESC migration and invasion, and these effects were inhibited by the IL-1 receptor-1 antagonist anakinra. Knockdown of each of the 3 PA system members also inhibited ESC migration and invasion. Knockdown of these PA system members further attenuated the impact of IL-1β on migration and invasion, suggesting that they mediated the promigration and proinvasion effects of IL-1β. To supplement the cell culture work, immunohistochemistry was performed on tissue sections of endometriotic epithelium/stroma: uPA, PAI-1, and IL-1β histoscores were not found to be correlated with each other.
Conclusion(s)
In primary cultures of ESCs, IL-1β induces migration and invasion, which is mediated by PA system members and inhibited by the drug anakinra. However, the immunohistochemistry expression of IL-1β, urokinase plasminogen inhibitor-1, and PAI-1 were not correlated, suggesting other regulatory mechanisms for PA system members. Inhibition of IL-1β (e.g., with anakinra) may have potential as a novel treatment approach for the migration/invasion of endometriosis.