IL10+/+ AND IL10-/- TROPHOBLAST CELLS PROLIFERATION, MIGRATION AND INVASION DURING HYPERGLYCEMIA AND EXPRESSION OF CENTRAL MOLECULES
Keywords:Hyperglycemia, IL-10, Trophoblast cell, TNF-alpha, LIF, MMP-9, NO
Successful embryo implantation requires a functional communication between a blastocyst and a receptive endometrium during a brief period known as the window of implantation. Under certain inflammatory conditions, such as diabetes, the window of implantation can be affected preventing normal implantation which could lead to pregnancy loss. The aim of our current study was to evaluate the role of IL-10, TNFα, LIF, MMP-9, and NO in implantation and to establish their possible impact on the functional ability of trophoblast cells under hyperglycemic conditions. For this reason, the experiments were conducted on trophoblast cells isolated from placentas of IL-10+/+ (C57BL/6J) and IL-10 -/-(B6.129P2-Il10tm1Cgn/J) pregnant mice. The cells were stimulated by IL-10, TNF-alpha and LIF, and the effect of glucose concentration on their functional activity and expression ability of several markers were determined. The results of our investigation showed that during hyperglycemia anti-inflammatory cytokine IL-10 occurs as an inhibitor of TNFα production and decreases oxidative stress. IL-10 regulates LIF and MMP expressions and evolves in the control of invasion and proliferation processes of trophoblast cells. In conclusion, IL-10 and TNF-alpha play a central role in the processes associated with implantation during hyperglycemia. IL-10 is a suppressor of hyperglycemia-induced trophoblast cell dysfunction and LIF, MMP-9, and NO may be critical players in it.
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