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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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Down-Regulation Endometriosis Endometrium Matrix Metalloproteinases Receptors, Interleukin-1 Type II Blotting, Western Blotting, Western Cell Line, Tumor Electrophoresis, Polyacrylamide Gel Endometriosis Endometriosis Endometrium Female Fluorescent Antibody Technique Humans Interleukin-1beta Interleukin-1beta Matrix Metalloproteinase 2 Matrix Metalloproteinase 2 Matrix Metalloproteinase 9

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europepmc
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