566 Cell Technologies in Biology and Medicine, No. 4, February, 2014 0007-4888/14/1564-0566 © 2014 Springer Science+Business Media New York Effect of Factors Produced by the Placenta on Cytokine Secretion by THP-1 Cells Cultured on a 3D Scaffold Ya. S. Onokhina, T. Yu. L’vova, D. Z. Tsitskarava, D. A. Koren’kov, S. A. Sel’kov, and D. I. Sokolov Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 4, pp. 217-222, October, 2013 Original article submitted January 10, 2012 We compared the effects of soluble products from the placenta obtained from women with normal pregnancy and pregnancy complicated by preeclampsia on cytokine secretion by THP-1 cells cultured on a 3D Matrigel scaffold. In the presence of soluble products from all placentas, the cells actively secreted IL-8, MCP-1, and soluble forms of CD14, TNFRI, and TNFRII receptors. Secretion of VEGF was below the spontaneous level. Secretion of IL-6 by THP-1 cells after incubation with soluble products of the placentas obtained during weeks 9-11 of physiological pregnancy and 38-39 of pregnancy complicated by preeclampsia sur- passed the spontaneous level. In the presence of soluble factors of trimester I placentas, secre- tion of IL-6 and soluble form of TNFRI receptor was higher than in the presence of trimester III placental factors. Secretion of IL-6 by THP-1 cells was higher, while secretion of soluble TNFRII receptor was lower in the presence of placentas from women with preeclampsia in comparison with physiological pregnancy. Key Words: preeclampsia; placenta; macrophages; cytokines D. O. Ott Research Institute of Obstetrics and Gynecology, North- Western Division of the Russian Academy of Medical Sciences, St. Petersburg, Russia. Address for correspondence: Falcojugger@ yandex.ru. D. I. SOKOLOV Decidual macrophages constituting ~25-30% maternal leukocyte pool in the uterine tissues play a special role in placenta formation [25]. Moreover, macrophages of fetal origin are present in chorionic villi [1]. It was demonstrated that decidual and placental macrophages in physiological pregnancy exhibit immunosuppressive properties, in particular, they secrete anti-inflammatory cytokines, expression of indoleamine-2,3 dioxygenase involved in microenvironmental tryptophan depriva- tion, suppression of NO-synthase activity via activa- tion of substrate competitor arginase [16]. Moreover, macrophages are characterized by enhanced expres- sion of innate immunity receptor, scavenger receptors, and macrophage mannose receptors, participating in removal of apoptotic cells and maintenance of tissue homeostasis at the fetoplacental barrier [16]. Phago- cytosis of apoptotic cells by placental and decidual macrophages secretion of IL-10 and TGF-β improv- ing viability of trophoblast cells [22]. Decidual and placental macrophages also participate in remodel- ing of the vascular bed in the endometrium. During physiological pregnancy, decidual macrophages are located in the uterine stroma around spiral arteries and invasive trophoblast cells [16]. Preeclampsia is accompanied by disturbances in the mechanisms of tolerance of the maternal immune system to semi- allogenic fetal tissue. Decidual and placental mac- rophages are activated by IFN-γ secreted by uterine NK cells [2]. Macrophages secrete pro-inflammatory cytokines, thus stimulating apoptosis of the tropho- blast and endothelial cells [22]. In preeclampsia, the number of decidual macrophages increases and they shield spiral arteries from invasive trophoblast cells, which leads to insufficient vascular remodeling [16]. Angiogenesis in the placenta is accompanied by abun- dant infiltration of the uterine tissues with monocytes and macrophages migrating from maternal peripheral blood; these cells produce matrix metalloproteinases