Increased expression of monocyte chemotactic protein-1 in the endometrium of women with endometriosis

Abstract The pathogenesis of endometriosis, a disease widely believed to arise from an aberrant growth of endometrial tissue outside the uterus, is still unclear. We have previously observed that cytokine-stimulated endometrial cells of women with endometriosis secrete in vitro increased amounts of monocyte chemotactic protein-1 (MCP-1). This factor may be important in the recruitment and activation of peritoneal macrophages observed in endometriosis patients. The present study reports that, in the presence of the disease, such an up-regulation of MCP-1 expression arises in vivo and can be encountered in situ in the intrauterine endometrium. In women with endometriosis, MCP-1 expression was elevated in endometrial glands, both at the level of the protein (immunohistochemistry) and the mRNA (in situ hybridization). This was observed throughout the menstrual cycle and varied according to the stage of the disease. These findings strongly argue in favor of the presence of pathophysiological changes in the eutopic endometrium of patients with endometriosis and make plausible MCP-1 as a key effector cell mediator involved in the pathogenesis of the disease. Full text PDFImages in this article Selected References These references are in PubMed. This may not be the complete list of references from this article. - Akoum A., Lemay A., Brunet C., Hébert J. Cytokine-induced secretion of monocyte chemotactic protein-1 by human endometriotic cells in culture. The Groupe d'Investigation en Gynécologie. Am J Obstet Gynecol. 1995 Feb;172(2 Pt 1):594–600. doi: 10.1016/0002-9378(95)90578-2. [DOI] [PubMed] [Google Scholar] - Akoum A., Lemay A., McColl S. R., Paradis I., Maheux R. Increased monocyte chemotactic protein-1 level and activity in the peripheral blood of women with endometriosis. Le Groupe d'Investigation en Gynécologie. Am J Obstet Gynecol. 1996 Dec;175(6):1620–1625. doi: 10.1016/s0002-9378(96)70115-1. [DOI] [PubMed] [Google Scholar] - Akoum A., Lemay A., McColl S., Turcot-Lemay L., Maheux R. Elevated concentration and biologic activity of monocyte chemotactic protein-1 in the peritoneal fluid of patients with endometriosis. Fertil Steril. 1996 Jul;66(1):17–23. [PubMed] [Google Scholar] - Arici A., Oral E., Attar E., Tazuke S. I., Olive D. L. Monocyte chemotactic protein-1 concentration in peritoneal fluid of women with endometriosis and its modulation of expression in mesothelial cells. Fertil Steril. 1997 Jun;67(6):1065–1072. doi: 10.1016/s0015-0282(97)81440-9. [DOI] [PubMed] [Google Scholar] - Blumenkrantz M. J., Gallagher N., Bashore R. A., Tenckhoff H. Retrograde menstruation in women undergoing chronic peritoneal dialysis. Obstet Gynecol. 1981 May;57(5):667–670. [PubMed] [Google Scholar] - Braun D. P., Gebel H., House R., Rana N., Dmowski N. P. Spontaneous and induced synthesis of cytokines by peripheral blood monocytes in patients with endometriosis. Fertil Steril. 1996 Jun;65(6):1125–1129. [PubMed] [Google Scholar] - Braun D. P., Muriana A., Gebel H., Rotman C., Rana N., Dmowski W. P. Monocyte-mediated enhancement of endometrial cell proliferation in women with endometriosis. Fertil Steril. 1994 Jan;61(1):78–84. doi: 10.1016/s0015-0282(16)56456-5. [DOI] [PubMed] [Google Scholar] - Dizerega G. S., Barber D. L., Hodgen G. D. Endometriosis: role of ovarian steroids in initiation, maintenance, and suppression. Fertil Steril. 1980 Jun;33(6):649–653. doi: 10.1016/s0015-0282(16)44780-1. [DOI] [PubMed] [Google Scholar] - Dmowski W. P., Gebel H. M., Braun D. P. The role of cell-mediated immunity in pathogenesis of endometriosis. Acta Obstet Gynecol Scand Suppl. 1994;159:7–14. [PubMed] [Google Scholar] - Eisermann J., Gast M. J., Pineda J., Odem R. R., Collins J. L. Tumor necrosis factor in peritoneal fluid of women undergoing laparoscopic surgery. Fertil Steril. 1988 Oct;50(4):573–579. doi: 10.1016/s0015-0282(16)60185-1. [DOI] [PubMed] [Google Scholar] - FREY G. H. The familial occurrence of endometriosis; report of five instances and review of the literature. Am J Obstet Gynecol. 1957 Feb;73(2):418–421. doi: 10.1016/s0002-9378(16)37364-1. [DOI] [PubMed] [Google Scholar] - Fakih H., Baggett B., Holtz G., Tsang K. Y., Lee J. C., Williamson H. O. Interleukin-1: a possible role in the infertility associated with endometriosis. Fertil Steril. 1987 Feb;47(2):213–217. [PubMed] [Google Scholar] - Gebel H. M., Rana N., Braun D. P., Dmowski W. P. Differential expression of VLA beta 1 (CD29) on monocytes from patients with endometriosis. Am J Reprod Immunol. 1995 Nov;34(5):317–322. doi: 10.1111/j.1600-0897.1995.tb00958.x. [DOI] [PubMed] [Google Scholar] - Gleicher N., el-Roeiy A., Confino E., Friberg J. Is endometriosis an autoimmune disease? Obstet Gynecol. 1987 Jul;70(1):115–122. [PubMed] [Google Scholar] - Halme J., Becker S., Hammond M. G., Raj M. H., Raj S. Increased activation of pelvic macrophages in infertile women with mild endometriosis. Am J Obstet Gynecol. 1983 Feb 1;145(3):333–337. doi: 10.1016/0002-9378(83)90720-2. [DOI] [PubMed] [Google Scholar] - Halme J., Hammond M. G., Hulka J. F., Raj S. G., Talbert L. M. Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gynecol. 1984 Aug;64(2):151–154. [PubMed] [Google Scholar] - Halme J., Mathur S. Local autoimmunity in mild endometriosis. Int J Fertil. 1987 Jul-Aug;32(4):309–311. [PubMed] [Google Scholar] - Halme J., White C., Kauma S., Estes J., Haskill S. Peritoneal macrophages from patients with endometriosis release growth factor activity in vitro. J Clin Endocrinol Metab. 1988 May;66(5):1044–1049. doi: 10.1210/jcem-66-5-1044. [DOI] [PubMed] [Google Scholar] - Haney A. F., Jenkins S., Weinberg J. B. The stimulus responsible for the peritoneal fluid inflammation observed in infertile women with endometriosis. Fertil Steril. 1991 Sep;56(3):408–413. doi: 10.1016/s0015-0282(16)54532-4. [DOI] [PubMed] [Google Scholar] - Haney A. F., Muscato J. J., Weinberg J. B. Peritoneal fluid cell populations in infertility patients. Fertil Steril. 1981 Jun;35(6):696–698. doi: 10.1016/s0015-0282(16)45567-6. [DOI] [PubMed] [Google Scholar] - Khorram O., Taylor R. N., Ryan I. P., Schall T. J., Landers D. V. Peritoneal fluid concentrations of the cytokine RANTES correlate with the severity of endometriosis. Am J Obstet Gynecol. 1993 Dec;169(6):1545–1549. doi: 10.1016/0002-9378(93)90433-j. [DOI] [PubMed] [Google Scholar] - Lawrence J. B., Singer R. H. Quantitative analysis of in situ hybridization methods for the detection of actin gene expression. Nucleic Acids Res. 1985 Mar 11;13(5):1777–1799. doi: 10.1093/nar/13.5.1777. [DOI] [PMC free article] [PubMed] [Google Scholar] - Leonard E. J., Yoshimura T. Human monocyte chemoattractant protein-1 (MCP-1). Immunol Today. 1990 Mar;11(3):97–101. doi: 10.1016/0167-5699(90)90035-8. [DOI] [PubMed] [Google Scholar] - Lessey B. A., Castelbaum A. J., Sawin S. W., Buck C. A., Schinnar R., Bilker W., Strom B. L. Aberrant integrin expression in the endometrium of women with endometriosis. J Clin Endocrinol Metab. 1994 Aug;79(2):643–649. doi: 10.1210/jcem.79.2.7519194. [DOI] [PubMed] [Google Scholar] - Liu D. T., Hitchcock A. Endometriosis: its association with retrograde menstruation, dysmenorrhoea and tubal pathology. Br J Obstet Gynaecol. 1986 Aug;93(8):859–862. doi: 10.1111/j.1471-0528.1986.tb07995.x. [DOI] [PubMed] [Google Scholar] - Malinak L. R., Buttram V. C., Jr, Elias S., Simpson J. L. Heritage aspects of endometriosis. II. Clinical characteristics of familial endometriosis. Am J Obstet Gynecol. 1980 Jun 1;137(3):332–337. [PubMed] [Google Scholar] - McLaren J., Prentice A., Charnock-Jones D. S., Millican S. A., Müller K. H., Sharkey A. M., Smith S. K. Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids. J Clin Invest. 1996 Jul 15;98(2):482–489. doi: 10.1172/JCI118815. [DOI] [PMC free article] [PubMed] [Google Scholar] - Mehrabian M., Sparkes R. S., Mohandas T., Fogelman A. M., Lusis A. J. Localization of monocyte chemotactic protein-1 gene (SCYA2) to human chromosome 17q11.2-q21.1. Genomics. 1991 Jan;9(1):200–203. doi: 10.1016/0888-7543(91)90239-b. [DOI] [PubMed] [Google Scholar] - Noble L. S., Simpson E. R., Johns A., Bulun S. E. Aromatase expression in endometriosis. J Clin Endocrinol Metab. 1996 Jan;81(1):174–179. doi: 10.1210/jcem.81.1.8550748. [DOI] [PubMed] [Google Scholar] - Olive D. L., Montoya I., Riehl R. M., Schenken R. S. Macrophage-conditioned media enhance endometrial stromal cell proliferation in vitro. Am J Obstet Gynecol. 1991 Apr;164(4):953–958. [PubMed] [Google Scholar] - Oosterlynck D. J., Cornillie F. J., Waer M., Vandeputte M., Koninckx P. R. Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium. Fertil Steril. 1991 Jul;56(1):45–51. doi: 10.1016/s0015-0282(16)54414-8. [DOI] [PubMed] [Google Scholar] - Ota H., Igarashi S., Hayakawa M., Matsui T., Tanaka H., Tanaka T. Effect of danazol on the immunocompetent cells in the eutopic endometrium in patients with endometriosis: a multicenter cooperative study. Fertil Steril. 1996 Mar;65(3):545–551. doi: 10.1016/s0015-0282(16)58151-5. [DOI] [PubMed] [Google Scholar] - Rana N., Braun D. P., House R., Gebel H., Rotman C., Dmowski W. P. Basal and stimulated secretion of cytokines by peritoneal macrophages in women with endometriosis. Fertil Steril. 1996 May;65(5):925–930. [PubMed] [Google Scholar] - Rock J. A., Markham S. M. Pathogenesis of endometriosis. Lancet. 1992 Nov 21;340(8830):1264–1267. doi: 10.1016/0140-6736(92)92959-j. [DOI] [PubMed] [Google Scholar] - Ryan I. P., Tseng J. F., Schriock E. D., Khorram O., Landers D. V., Taylor R. N. Interleukin-8 concentrations are elevated in peritoneal fluid of women with endometriosis. Fertil Steril. 1995 Apr;63(4):929–932. [PubMed] [Google Scholar] - Schall T. J. Biology of the RANTES/SIS cytokine family. Cytokine. 1991 May;3(3):165–183. doi: 10.1016/1043-4666(91)90013-4. [DOI] [PubMed] [Google Scholar] - Somigliana E., Viganò P., Gaffuri B., Guarneri D., Busacca M., Vignali M. Human endometrial stromal cells as a source of soluble intercellular adhesion molecule (ICAM)-1 molecules. Hum Reprod. 1996 Jun;11(6):1190–1194. doi: 10.1093/oxfordjournals.humrep.a019353. [DOI] [PubMed] [Google Scholar] - Strathy J. H., Molgaard C. A., Coulam C. B., Melton L. J., 3rd Endometriosis and infertility: a laparoscopic study of endometriosis among fertile and infertile women. Fertil Steril. 1982 Dec;38(6):667–672. doi: 10.1016/s0015-0282(16)46691-4. [DOI] [PubMed] [Google Scholar] - Vernon M. W., Beard J. S., Graves K., Wilson E. A. Classification of endometriotic implants by morphologic appearance and capacity to synthesize prostaglandin F. Fertil Steril. 1986 Nov;46(5):801–806. [PubMed] [Google Scholar] - Viganò P., Vercellini P., Di Blasio A. M., Colombo A., Candiani G. B., Vignali M. Deficient antiendometrium lymphocyte-mediated cytotoxicity in patients with endometriosis. Fertil Steril. 1991 Nov;56(5):894–899. doi: 10.1016/s0015-0282(16)54661-5. [DOI] [PubMed] [Google Scholar] - Wingfield M., Macpherson A., Healy D. L., Rogers P. A. Cell proliferation is increased in the endometrium of women with endometriosis. Fertil Steril. 1995 Aug;64(2):340–346. doi: 10.1016/s0015-0282(16)57733-4. [DOI] [PubMed] [Google Scholar] - Yoshimura T., Leonard E. J. Identification of high affinity receptors for human monocyte chemoattractant protein-1 on human monocytes. J Immunol. 1990 Jul 1;145(1):292–297. [PubMed] [Google Scholar] - Zeller J. M., Henig I., Radwanska E., Dmowski W. P. Enhancement of human monocyte and peritoneal macrophage chemiluminescence activities in women with endometriosis. Am J Reprod Immunol Microbiol. 1987 Mar;13(3):78–82. doi: 10.1111/j.1600-0897.1987.tb00097.x. [DOI] [PubMed] [Google Scholar]