Regulation of Monocyte Chemotactic Protein-1 Expression in Human Endometrial Endothelial Cells by Sex Steroids: A Potential Mechanism for Leukocyte Recruitment in Endometriosis

Abstract

The main aim of this study is to describe the in vivo temporal and spatial expression of monocyte chemotactic protein 1 (MCP-1) in human endometrial endothelial cells (HEECs) and to compare the in vitro regulation of MCP-1 expression by sex steroids in HEECs from women with or without endometriosis. Eutopic endometrial tissues and endometriosis implants were grouped according to the menstrual cycle phase and were examined by immunohistochemistry for MCP-1 expression. No significant difference was observed for MCP-1 immunoreactivity in the endothelial cells of eutopic endometrium of women with endometriosis when compared to endometrium of women without endometriosis and to endometriosis implants. For in vitro studies, the purity of cultured HEECs (90%-95%) was confirmed by immunocytochemistry using endothelium-specific markers CD31 and CD146. The effects of estradiol (5 × 10^{— 8} mol/L), progesterone (10^—7 mol/L), or both on MCP-1 messenger RNA (mRNA) and protein levels were analyzed by reverse transcriptase—polymerase chain reaction (RT-PCR) analysis and enzyme-linked immunosorbent serologic assay (ELISA), respectively. Sex steroids did not have significant effect on MCP-1 mRNA and protein expression in HEECs from women without endometriosis. However, we observed that the sex steroid treatment stimulated MCP-1 mRNA and protein expression in HEECs from women with endometriosis (P < .05). We postulate that the stimulation of chemokine expression by sex steroids in the endometrial endothelial cells in women with endometriosis may play a central role in recruiting mononuclear cells, therefore contributing to the inflammatory aspect of endometriosis.

Keywords

Endometriosis MCP-1 human endometrial endothelial cells sex steroids estrogen progesterone.

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References

Tabibzadeh S. Human endometrium: an active site of cytokine production and action. Endoc Rev. 1991;12(3): 272-290.

Garcia-Velasco JA , Seli E. , Arici A. Regulation of monocyte chemotactic protein-1 expression in human endometrial stromal cells by integrin-dependent cell adhesion . Biol Reprod. 1999;61(2):548-552.

Arici A. , Oral E. , Attar E. , Tazuke SI , Olive DL Monocyte chemotactic protein-1 concentration in peritoneal fluid of women with endometriosis and its modulation of expression in mesothelial cells. Fert Steril. 1997;67(6):1065-1072.

Arici A. , Senturk LM , Seli E. , Bahtiyar MO , Kim G. Regulation of monocyte chemotactic protein-1 expression in human endometrial stromal cells by estrogen and progesterone. Biol Reprod. 1999;61(1):85-90.

Halme J. , Hammond MG , Hulka JF , Raj SG , Talbert LM Retrograde menstruation in healthy women and in patients with endometriosis . Obstet Gynecol. 1984;64(2):151-154.

Jones RL , Kelly RW , Critchley HO Chemokine and cyclooxygenase-2 expression in human endometrium coincides with leukocyte accumulation. Hum Reprod. 1997; 12(6):1300-1306.

Ramey JW , Archer DF Peritoneal fluid: its relevance to the development of endometriosis [see comment] . Fertil Steril. 1993;60(1):1-14.

Arici A. , Head JR , MacDonald PC , Casey ML Regulation of interleukin-8 gene expression in human endometrial cells in culture. Mol Cell Endocrinol. 1993;94(2):195-204.

St Croix B. , Rago C. , Velculescu V. , et al. Genes expressed in human tumor endothelium [see comment]. Science 2000;289:1197-202.

10.

Kayisli UA , Luk J. , Ozlem GK , Demir R. , Arici A. Regulation of Angiogenic Activity of Human Endometrial Endothelial Cells in Culture by Ovarian Steriods. J Clin Endocrinol Metabol. 2004;89(11):5794-5802.

11.

Haney AF , Muscato JJ , Weinberg JB Peritoneal fluid cell populations in infertility patients. Fertil Steril. 1981;35(6):696-698.

12.

Olive DL , Weinberg JB , Haney AF Peritoneal macrophages and infertility: the association between cell number and pelvic pathology. Fertil Steril. 1985;44(6):772-777.

13.

Gazvani MR , Christmas S. , Quenby S. , Kirwan J. , Johnson PM , Kingsland CR Peritoneal fluid concentrations of interleukin-8 in women with endometriosis: relationship to stage of disease. Hum Reprod. 1998; 13(7):1957-1961.

14.

Fu H. , Wu WC , Hu HD , Liu XJ Effects of placental growth factor on the secreation of proinflammatory cytochemokines in vascular endothelial cells. Sichuan Da Xue Xue Bao Yi Xue Ban. 2009;40(3):385-389.

15.

Liu ZB , Shen X. Thioredoxin reductase 1 upregulates MCP-1 release in human endothelial cells . Biochem Biophys Res Commun. 2009;386(4):703-708.

16.

Ingegno MD , Money SR , Thelmo W. , et al. Progesterone receptors in the human heart and great vessels . Lab Invest. 1988;59(3):353-356.

17.

Vaquez F. , Rodriguez-Manzaneque JC , Lydon JP , Edwards DP , O’ Malley BW , Irela-Arispe ML Progesterone regulates proliferation of endothelial cells. J Biol Chem. 1999; 274(4):2185-2192.

18.

Burney RO , Talbi S. , Hamilton AD , et al. Gene expression analysis of endometrium revelas progesterone resistance and candidate susceptibility genes n women with endometriosis. Endocrinology. 2007;148(8):3814-3826.

19.

Goebeler M. , Gillitzer R. , Kilian K. , et al. Multiple signaling pathways regulate NF-kappaB-dependent transcription of the monocyte chemoattractant protein-1 gene in primary endothelial cells. Blood. 2001;97(1):46-55.

20.

Tse AK , Wan CK , Zhu GY , et al. Magnolol suppresses NFkappaB activation and NF-kappaB regulated gene expression through inhibition of IkappaB kinase activation. Mol Immunol. 2007;44(10):2647-2658.

21.

Ichikawa H. , Takada Y. , Murakami A. , Aggarwal BB. Identification of a novel blocker of I kappa B alpha kinase that enhances cellular apoptosis and inhibits cellular invasion through suppression of NF-kappa B-regulated gene products. J Immunol. 2005;174(11):7383-7392.

22.

Noble LS , Simpson ER , Johns A. , Bulun SE Aromatase expression in endometriosis. J Clin Endocrinol Metab . 1996; 81(1):174-179.

23.

Sampson J. Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obst Gynecol. 1927;14:422-469.

24.

Lebovic DI , Mueller MD , Taylor RN Immunobiology of endometriosis. Fertil Steril. 2001;75(1):1-10.