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Macrophage migration inhibitory factor antagonist blocks the development of endometriosis in vivo.
PLoS One 2012; 7(5):e37264Plos

Abstract

Endometriosis, a disease of reproductive age women, is a major cause of infertility, menstrual disorders and pelvic pain. Little is known about its etiopathology, but chronic pelvic inflammation is a common feature in affected women. Beside symptomatic treatment of endometriosis-associated pain, only two main suboptimal therapeutic approaches (hormonal and invasive surgery) are generally recommended to patients and no specific targeted treatment is available. Our studies led to the detection of a marked increase in the expression of macrophage migration inhibitory factor (MIF) in the eutopic endometrium, the peripheral blood and the peritoneal fluid of women with endometriosis, and in early, vascularized and active endometriotic lesions. Herein, we developed a treatment model of endometriosis, where human endometrial tissue was first allowed to implant into the peritoneal cavity of nude mice, to assess in vivo the effect of a specific antagonist of MIF (ISO-1) on the progression of endometriosis and evaluate its efficacy as a potential therapeutic tool. Administration of ISO-1 led to a significant decline of the number, size and in situ dissemination of endometriotic lesions. We further showed that ISO-1 may act by significantly inhibiting cell adhesion, tissue remodeling, angiogenesis and inflammation as well as by altering the balance of pro- and anti-apoptotic factors. Actually, mice treatment with ISO-1 significantly reduced the expression of cell adhesion receptors αv and β3 integrins (P<0.05), matrix metalloproteinases (MMP) 2 and 9 (P<0.05), vascular endothelial cell growth factor (VEGF) (P<0.01), interleukin 8 (IL8) (P<0.05), cyclooxygenease (COX)2 (P<0.001) and the anti-apoptotic protein Bcl2 (P<0.01), but significantly induced the expression of Bax (P<0.05), a potent pro-apoptotic protein. These data provide evidence that specific inhibition of MIF alters endometriotic tissue growth and progression in vivo and may represent a promising potential therapeutic avenue.

Authors+Show Affiliations

Endocrinologie de la Reproduction, Centre de Recherche, Hôpital Saint-François d'Assise, CHUQ, Quebec City, Québec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22649515

Citation

Khoufache, Khaled, et al. "Macrophage Migration Inhibitory Factor Antagonist Blocks the Development of Endometriosis in Vivo." PloS One, vol. 7, no. 5, 2012, pp. e37264.
Khoufache K, Bazin S, Girard K, et al. Macrophage migration inhibitory factor antagonist blocks the development of endometriosis in vivo. PLoS ONE. 2012;7(5):e37264.
Khoufache, K., Bazin, S., Girard, K., Guillemette, J., Roy, M. C., Verreault, J. P., ... Akoum, A. (2012). Macrophage migration inhibitory factor antagonist blocks the development of endometriosis in vivo. PloS One, 7(5), pp. e37264. doi:10.1371/journal.pone.0037264.
Khoufache K, et al. Macrophage Migration Inhibitory Factor Antagonist Blocks the Development of Endometriosis in Vivo. PLoS ONE. 2012;7(5):e37264. PubMed PMID: 22649515.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Macrophage migration inhibitory factor antagonist blocks the development of endometriosis in vivo. AU - Khoufache,Khaled, AU - Bazin,Sylvie, AU - Girard,Karine, AU - Guillemette,Julie, AU - Roy,Marie-Christine, AU - Verreault,Jean-Pierre, AU - Al-Abed,Yousef, AU - Foster,Warren, AU - Akoum,Ali, Y1 - 2012/05/23/ PY - 2011/10/21/received PY - 2012/04/19/accepted PY - 2012/6/1/entrez PY - 2012/6/1/pubmed PY - 2012/10/10/medline SP - e37264 EP - e37264 JF - PloS one JO - PLoS ONE VL - 7 IS - 5 N2 - Endometriosis, a disease of reproductive age women, is a major cause of infertility, menstrual disorders and pelvic pain. Little is known about its etiopathology, but chronic pelvic inflammation is a common feature in affected women. Beside symptomatic treatment of endometriosis-associated pain, only two main suboptimal therapeutic approaches (hormonal and invasive surgery) are generally recommended to patients and no specific targeted treatment is available. Our studies led to the detection of a marked increase in the expression of macrophage migration inhibitory factor (MIF) in the eutopic endometrium, the peripheral blood and the peritoneal fluid of women with endometriosis, and in early, vascularized and active endometriotic lesions. Herein, we developed a treatment model of endometriosis, where human endometrial tissue was first allowed to implant into the peritoneal cavity of nude mice, to assess in vivo the effect of a specific antagonist of MIF (ISO-1) on the progression of endometriosis and evaluate its efficacy as a potential therapeutic tool. Administration of ISO-1 led to a significant decline of the number, size and in situ dissemination of endometriotic lesions. We further showed that ISO-1 may act by significantly inhibiting cell adhesion, tissue remodeling, angiogenesis and inflammation as well as by altering the balance of pro- and anti-apoptotic factors. Actually, mice treatment with ISO-1 significantly reduced the expression of cell adhesion receptors αv and β3 integrins (P<0.05), matrix metalloproteinases (MMP) 2 and 9 (P<0.05), vascular endothelial cell growth factor (VEGF) (P<0.01), interleukin 8 (IL8) (P<0.05), cyclooxygenease (COX)2 (P<0.001) and the anti-apoptotic protein Bcl2 (P<0.01), but significantly induced the expression of Bax (P<0.05), a potent pro-apoptotic protein. These data provide evidence that specific inhibition of MIF alters endometriotic tissue growth and progression in vivo and may represent a promising potential therapeutic avenue. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22649515/Macrophage_migration_inhibitory_factor_antagonist_blocks_the_development_of_endometriosis_in_vivo_ L2 - http://dx.plos.org/10.1371/journal.pone.0037264 DB - PRIME DP - Unbound Medicine ER -