Stable inhibition of interleukin 1 receptor type II in Ishikawa cells augments secretion of matrix metalloproteinases: possible role in endometriosis pathophysiology
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Stable inhibition of IL1R2 in Ishikawa cells reduced IL1R2 expression and increased secretion of MMP-2 and MMP-9, while decreasing TIMP-1 secretion.
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Abstract
Our previous studies showed a marked deficiency in interleukin 1 receptor type II (IL1R2) in the endometrial tissue of women with endometriosis, particularly in epithelial cells. We believe that such a deficiency in IL1R2, a potent and specific IL1 inhibitor, makes endometrial cells more sensitive to IL1 and less capable of buffering the cytokine's effects, which may lead to functional changes that favor endometriosis development. The main objective of our study was to stably inhibit IL1R2 expression in endometrial cells in order to evaluate the role of IL1R2 deficiency in endometriosis pathophysiology. Stable clones of Ishikawa adenocarcinoma endometrial cells transfected with IL1R2 antisense and showing downregulation of IL1R2 protein expression, or with the empty expression vector alone and showing no noticeable difference in IL1R2 expression, were selected. The downregulation of IL1R2 expression in IL1R2 antisense transfectants when compared with control cells was confirmed by ELISA, Western blot and immunofluorescence. In these cells, IL1R2 expression was markedly reduced, compared with non-transfected cells or cells transfected with the empty vector, and there was a significant increase in the basal and the IL1-beta (IL1B)-induced levels of matrix metalloproteinase (MMP)-2 and MMP-9 secretion. Furthermore, a significant decrease in IL1B-induced secretion of tissue inhibitor of MMPs-1, a known MMP-9 inhibitor, was observed. These in vitro data make plausible a role for IL1R2 deficiency in the capability of endometrial cells to invade the host tissue and develop in ectopic locations.
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Cited by (18)
- Biomaterial Tools for Modeling Endometriosis 2026
- Therapeutic Mechanism and Clinical Observation of Traditional Chinese Medicine Combined with Interventional Recanalization for Tubal Infertility 2021
- Effects of CDKN2B-AS1 on cellular proliferation, invasion and AKT3 expression are attenuated by miR-424-5p in a model of ovarian endometriosis 2021
- Peer Review #3 of "TET1 may contribute to hypoxia-induced epithelial to mesenchymal transition of endometrial epithelial cells in endometriosis (v0.2)" 2020
- Peer Review #3 of "TET1 may contribute to hypoxia-induced epithelial to mesenchymal transition of endometrial epithelial cells in endometriosis (v0.1)" 2020
- Peer Review #2 of "TET1 may contribute to hypoxia-induced epithelial to mesenchymal transition of endometrial epithelial cells in endometriosis (v0.2)" 2020
- Peer Review #2 of "TET1 may contribute to hypoxia-induced epithelial to mesenchymal transition of endometrial epithelial cells in endometriosis (v0.1)" 2020
- TET1 may contribute to hypoxia-induced epithelial to mesenchymal transition of endometrial epithelial cells in endometriosis 2020
- microRNA-141 inhibits TGF-β1-induced epithelial-to-mesenchymal transition through inhibition of the TGF-β1/SMAD2 signalling pathway in endometriosis 2020
- Peer Review #1 of "TET1 may contribute to hypoxia-induced epithelial to mesenchymal transition of endometrial epithelial cells in endometriosis (v0.1)" 2020
- Peer Review #1 of "TET1 may contribute to hypoxia-induced epithelial to mesenchymal transition of endometrial epithelial cells in endometriosis (v0.2)" 2020
- Comparative characteristics of eutopic and ectopic endometrium in patients with ovarian endometric cysts and normal endometrium 2018
- Upregulation of CFTR in patients with endometriosis and its involvement in NFκB-uPAR dependent cell migration 2017
- TNF<i>α</i> and IL1<i>β</i> Stimulate Differential Gene Expression in Endometrial Stromal Cells 2015
- Oestrogen‐induced angiogenesis promotes adenomyosis by activating the <scp>S</scp>lug‐<scp>VEGF</scp> axis in endometrial epithelial cells 2014
- Interleukin-1β induces cyclooxygenase-2 expression and promotes the invasive ability of human mesenchymal stem cells derived from ovarian endometrioma 2011
- Distinct expression of the soluble and the membrane-bound forms of interleukin-1 receptor accessory protein in the endometrium of women with endometriosis 2011
- Expression of interleukin-1 (IL-1) ligands system in the most common endometriosis-associated ovarian cancer subtypes 2010
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