title: Soluble human IL-1 receptor type 2 inhibits ectopic endometrial tissue implantation and growth: identification of a novel potential target for endometriosis treatment.
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: Laboratory of Reproductive Endocrinology, Hôpital Saint-François d'Assise, Centre Hospitalier Universitaire de Québec, Quebec City, Quebec, Canada.
authors: Khaled
authors: K
authors: Khoufache
authors: Patrick Kibangou
authors: PK
authors: Bondza
authors: Noria
authors: N
authors: Harir
authors: Marleen
authors: M
authors: Daris
authors: Mathieu
authors: M
authors: Leboeuf
authors: Jacques
authors: J
authors: Mailloux
authors: Madeleine
authors: M
authors: Lemyre
authors: Warren
authors: W
authors: Foster
authors: Ali
authors: A
authors: Akoum
mesh_terms: D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D001706:Biopsy; D001835:Body Weight; D002448:Cell Adhesion; D002465:Cell Movement; D004715:Endometriosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D004717:Endometrium / Q000254:growth & development* / Q000473:pathology / Q000637:transplantation*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D053574:Receptors, Interleukin-1 Type II / Q000627:therapeutic use*; D012995:Solubility; D013194:Staining and Labeling; D016019:Survival Analysis
chemical_list: D043925:Angiogenesis Inducing Agents; D012333:RNA, Messenger; D053574:Receptors, Interleukin-1 Type II