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Soluble human IL-1 receptor type 2 inhibits ectopic endometrial tissue implantation and growth: identification of a novel potential target for endometriosis treatment.
Am J Pathol 2012; 181(4):1197-205AJ

Abstract

Endometriosis is often associated with a chronic pelvic immuno-inflammatory process, which is closely related to disease pathogenesis and major symptoms. Our studies led to the detection of a marked imbalance between IL-1 and its natural inhibitor IL-1 receptor type 2 (IL1R2) in women with endometriosis. This points to a deficiency in the local control of IL-1 that, in view of the cytokine's elevated levels and potent proinflammatory, angiogenic, and growth-promoting effects, may contribute to endometriosis development. Using an in vivo model in which human endometrial tissue was inoculated into nude mice and left to establish before any further treatment, our data showed that sIL1R2 interferes with the capability of endometrial tissue to invade, grow, disseminate, and stimulate angiogenesis into the host tissue. sIL1R2 significantly down-regulated the expression of major cell adhesion receptors (αv and β3 integrins), matrix metalloproteinases (MMP-2 and -9), and vascular endothelial cell growth factor. Interestingly, treatment with sILR2 (5 μg/kg) led to a concomitant upregulation of matrix metalloproteinases natural inhibitors (TIMP1 and TIMP2) and down-regulation of BclII, a potent anti-apoptotic protein. This creates an imbalance between pro- and anti-proteolytic and apoptotic factors and may further contribute to IL1R2 growth-inhibitory effects. This study provides evidence that sIL1R2 alters ectopic endometrial tissue growth, remodeling, and survival in vivo and may represent an interesting potential therapeutic tool.

Authors+Show Affiliations

Laboratory of Reproductive Endocrinology, Hôpital Saint-François d'Assise, Centre Hospitalier Universitaire de Québec, Quebec City, Quebec, 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

22841820

Citation

Khoufache, Khaled, et al. "Soluble Human IL-1 Receptor Type 2 Inhibits Ectopic Endometrial Tissue Implantation and Growth: Identification of a Novel Potential Target for Endometriosis Treatment." The American Journal of Pathology, vol. 181, no. 4, 2012, pp. 1197-205.
Khoufache K, Bondza PK, Harir N, et al. Soluble human IL-1 receptor type 2 inhibits ectopic endometrial tissue implantation and growth: identification of a novel potential target for endometriosis treatment. Am J Pathol. 2012;181(4):1197-205.
Khoufache, K., Bondza, P. K., Harir, N., Daris, M., Leboeuf, M., Mailloux, J., ... Akoum, A. (2012). Soluble human IL-1 receptor type 2 inhibits ectopic endometrial tissue implantation and growth: identification of a novel potential target for endometriosis treatment. The American Journal of Pathology, 181(4), pp. 1197-205. doi:10.1016/j.ajpath.2012.06.022.
Khoufache K, et al. Soluble Human IL-1 Receptor Type 2 Inhibits Ectopic Endometrial Tissue Implantation and Growth: Identification of a Novel Potential Target for Endometriosis Treatment. Am J Pathol. 2012;181(4):1197-205. PubMed PMID: 22841820.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Soluble human IL-1 receptor type 2 inhibits ectopic endometrial tissue implantation and growth: identification of a novel potential target for endometriosis treatment. AU - Khoufache,Khaled, AU - Bondza,Patrick Kibangou, AU - Harir,Noria, AU - Daris,Marleen, AU - Leboeuf,Mathieu, AU - Mailloux,Jacques, AU - Lemyre,Madeleine, AU - Foster,Warren, AU - Akoum,Ali, Y1 - 2012/07/27/ PY - 2011/08/26/received PY - 2012/05/30/revised PY - 2012/06/26/accepted PY - 2012/7/31/entrez PY - 2012/7/31/pubmed PY - 2013/2/7/medline SP - 1197 EP - 205 JF - The American journal of pathology JO - Am. J. Pathol. VL - 181 IS - 4 N2 - Endometriosis is often associated with a chronic pelvic immuno-inflammatory process, which is closely related to disease pathogenesis and major symptoms. Our studies led to the detection of a marked imbalance between IL-1 and its natural inhibitor IL-1 receptor type 2 (IL1R2) in women with endometriosis. This points to a deficiency in the local control of IL-1 that, in view of the cytokine's elevated levels and potent proinflammatory, angiogenic, and growth-promoting effects, may contribute to endometriosis development. Using an in vivo model in which human endometrial tissue was inoculated into nude mice and left to establish before any further treatment, our data showed that sIL1R2 interferes with the capability of endometrial tissue to invade, grow, disseminate, and stimulate angiogenesis into the host tissue. sIL1R2 significantly down-regulated the expression of major cell adhesion receptors (αv and β3 integrins), matrix metalloproteinases (MMP-2 and -9), and vascular endothelial cell growth factor. Interestingly, treatment with sILR2 (5 μg/kg) led to a concomitant upregulation of matrix metalloproteinases natural inhibitors (TIMP1 and TIMP2) and down-regulation of BclII, a potent anti-apoptotic protein. This creates an imbalance between pro- and anti-proteolytic and apoptotic factors and may further contribute to IL1R2 growth-inhibitory effects. This study provides evidence that sIL1R2 alters ectopic endometrial tissue growth, remodeling, and survival in vivo and may represent an interesting potential therapeutic tool. SN - 1525-2191 UR - https://www.unboundmedicine.com/medline/citation/22841820/Soluble_human_IL_1_receptor_type_2_inhibits_ectopic_endometrial_tissue_implantation_and_growth:_identification_of_a_novel_potential_target_for_endometriosis_treatment_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(12)00497-X DB - PRIME DP - Unbound Medicine ER -