Interleukin-1β and plasminogen activating system members in endometriotic stromal cell migration/invasion

Fahad T Alotaibi, Sadaf Sediqi, Christian Klausen, Mohamed A Bedaiwy, Paul J Yong
F&S science · 2022 · vol. 4(1) , pp. 47–55 · doi:10.1016/j.xfss.2022.09.004 · PMID:36152991 · W4297878093
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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.

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mesh:D004715endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

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