Estradiol and Interleukin-1β Exert a Synergistic Stimulatory Effect on the Expression of the Chemokine Regulated upon Activation, Normal T Cell Expressed, and Secreted in Endometriotic Cells

Akoum A, Ali Akoum, André Lemay, Lemay A, Maheux R, Rodolphe Maheux
The Journal of clinical endocrinology and metabolism · 2002 · vol. 87(12) , pp. 5785–5792 · doi:10.1210/jc.2002-020106 · PMID:12466387 · W1980912607
article OA: bronze CC0 ⤵ 43 in-corpus citations
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Estradiol and IL-1beta synergistically stimulate RANTES expression and secretion in endometriotic cells by enhancing mRNA stability and transcription, exacerbating local inflammation.

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Abstract

Endometriosis, commonly associated with intraperitoneal inflammation, is estrogen dependent. Possible links between the immunoinflammatory and endocrine changes observed in endometriotic women have been poorly understood. In this study, we report that estradiol (E(2)) and IL-1beta exert a synergistic stimulatory action on RANTES (regulated upon activation, normal T cell expressed, and secreted) expression by endometriotic cells. Treatment of endometriotic cells with IL-1beta had a dose-dependent effect on RANTES protein secretion and mRNA steady state levels, whereas cell treatment with E(2) or progesterone had no detectable effect. Interestingly, treatment of endometriotic cells with E(2) before stimulation with IL-1beta resulted in a further increase in RANTES protein secretion and mRNA steady state levels, compared with IL-1beta alone, whereas treatment with progesterone did not significantly affect cell responsiveness to IL-1beta. Assessment of RANTES mRNA half-life revealed that cell pretreatment with E(2) enhanced RANTES mRNA stability and increased gene transcription as shown by run-on analysis. Immunohistochemical analysis of RANTES in endometriotic tissue showed immunostaining to be predominant in the stroma with no noticeable differences in tissues from the proliferative and secretory phase of the menstrual cycle. This appears to be consistent with the cell culture data and indicates that RANTES expression in endometriotic tissue is not subject to cyclic variation. These findings reveal a new regulatory mechanism by which IL-1beta produced by activated macrophages can in synergy with ovarian and locally produced E(2) lead to enhanced macrophage and T-lymphocyte recruitment, thereby exacerbating the local immunoinflammatory process. Furthermore, the findings provide a further evidence for a close relationship between the endocrine and immunological changes observed in endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Chemokine CCL5 Endometriosis Estradiol Interleukin-1 T-Lymphocytes Adolescent Adult Chemokine CCL5 Chemokine CCL5 Dose-Response Relationship, Drug Drug Synergism Endometriosis Endometriosis Estradiol Female Humans Immunohistochemistry Interleukin-1 Interleukin-1 Menstrual Cycle

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