mRNA-Binding Protein TIA-1 Reduces Cytokine Expression in Human Endometrial Stromal Cells and Is Down-Regulated in Ectopic Endometrium

Hakan Karalök, Karalok HM, Hakan Mete Karalok, Aydin E, Ebru Aydin, Ozlen Saglam, Saglam O, Torun A, Aysenur Torun, Ozlem Guzeloglu‐Kayisli, Ozlem Guzeloglu-Kayisli, Guzeloglu-Kayisli O, Maria D. Lalioti, Lalioti MD, Helena Kristiansson, Kristiansson H, Cindy M. Duke, Duke CM, Cindy M P Duke, Choe G, Gina Choe, Clare Flannery, Clare A. Flannery, Caleb B. Kallen, Seli E, Emre Seli
The Journal of clinical endocrinology and metabolism · 2014 · vol. 99(12) , pp. E2610–E2619 · doi:10.1210/jc.2013-3488 · PMID:25140393 · PMC4255110 · W2097612602
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mRNA-binding protein TIA-1 reduces cytokine expression in human endometrial cells and is downregulated in endometriosis tissue.

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Abstract

BACKGROUND: Cytokines and growth factors play important roles in endometrial function and the pathogenesis of endometriosis. mRNAs encoding cytokines and growth factors undergo rapid turnover; primarily mediated by adenosine- and uridine-rich elements (AREs) located in their 3'-untranslated regions. T-cell intracellular antigen (TIA-1), an mRNA-binding protein, binds to AREs in target transcripts, leading to decreased gene expression. OBJECTIVE: The purpose of this article was to determine whether TIA-1 plays a role in the regulation of endometrial cytokine and growth factor expression during the normal menstrual cycle and whether TIA-1 expression is altered in women with endometriosis. METHODS: Eutopic endometrial tissue obtained from women without endometriosis (n = 30) and eutopic and ectopic endometrial tissues from women with endometriosis (n = 17) were immunostained for TIA-1. Staining intensities were evaluated by histological scores (HSCOREs). The regulation of endometrial TIA-1 expression by immune factors and steroid hormones was studied by treating primary cultured human endometrial stromal cells (HESCs) with vehicle, lipopolysaccharide, TNF-α, IL-6, estradiol, or progesterone, followed by protein blot analyses. HESCs were engineered to over- or underexpress TIA-1 to test whether TIA-1 regulates IL-6 or TNF-α expression in these cells. RESULTS: We found that TIA-1 is expressed in endometrial stromal and glandular cells throughout the menstrual cycle and that this expression is significantly higher in the perimenstrual phase. In women with endometriosis, TIA-1 expression in eutopic and ectopic endometrium was reduced compared with TIA-1 expression in eutopic endometrium of unaffected control women. Lipopolysaccharide and TNF-α increased TIA-1 expression in HESCs in vitro, whereas IL-6 or steroid hormones had no effect. In HESCs, down-regulation of TIA-1 resulted in elevated IL-6 and TNF-α expression, whereas TIA-1 overexpression resulted in decreased IL-6 and TNF-α expression. CONCLUSIONS: Endometrial TIA-1 is regulated throughout the menstrual cycle, TIA-1 modulates the expression of immune factors in endometrial cells, and downregulation of TIA-1 may contribute to the pathogenesis of endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Cytokines Endometrium Poly(A)-Binding Proteins Poly(A)-Binding Proteins Stromal Cells Adult Cells, Cultured Cell Separation Cytokines Down-Regulation Endometriosis Endometriosis Endometrium Endometrium Endometrium Estrogens Estrogens Female Gene Expression Gene Expression

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