RESUMEN
Angiogenesis is a process of new blood vessel formation, which plays a significant role in carcinogenesis and the development of diseases associated with pathological neovascularization. An important role in the regulation of angiogenesis belongs to several key pathways such as VEGF-pathways, TGF-ß-pathways, and some others. Introduction of small interfering RNA (siRNA) against genes of pro-angogenic factors is a promising strategy for the therapeutic suppression of angiogenesis. These siRNA molecules need to be specifically delivered into endothelial cells, and non-viral carriers modified with cellular receptor ligands can be proposed as perspective delivery systems for anti-angiogenic therapy purposes. Here we used modular peptide carrier L1, containing a ligand for the CXCR4 receptor, for the delivery of siRNAs targeting expression of VEGFA, VEGFR1 and endoglin genes. Transfection properties of siRNA/L1 polyplexes were studied in CXCR4-positive breast cancer cells MDA-MB-231 and endothelial cells EA.Hy926. We have demonstrated the efficient down-regulation of endothelial cells migration and proliferation by anti-VEGFA, anti-VEGFR1, and anti-endoglin siRNA-induced silencing. It was found that the efficiency of anti-angiogenic treatment can be synergistically improved via the combinatorial delivery of anti-VEGFA and anti-VEGFR1 siRNAs. Thus, this approach can be useful for the development of therapeutic angiogenesis inhibition.
RESUMEN
PROBLEM: IL-11 is a cytokine with pleiotropic activities, including gestational effects. Whereas IL-11 production by maternal reproductive tissues is extensively studied, there is poor information about IL-11 sources in the fetal counterpart of the maternal-fetal unit. METHOD OF STUDY: We investigated the expression of IL-11 in the purified human term placenta macrophages, using flow cytometry and immunoenzyme assay. RESULTS: Intracellular IL-11 was detected in a substantial proportion of cultured CD68(+) cells (median 38%). IL-11 secretion by the placental macrophages was observed after 23-hr cultivation (median 4.3 pg/10(5) cells). Stimulation with lipopolysaccharide did not significantly change both intracellular expression and secretion of the cytokine. CONCLUSION: Demonstrated IL-11 expression by placental macrophages suggests that non-trophoblast cells contribute to IL-11 production at the maternal-fetal interface and thus account for the reproductive effects of the cytokine.