Investigation On The Correlation Between TREM-1 And Pathogenesis Of Preecampsia

Background Preeclampsia(PE)is one of the most common complications of pregnancy,which seriously harms the health of mothers and fetus.Excessive activation of maternal systemic inflammatory response is considered to be important in the development of PE.The triggering receptor expressed on myeloid cells-1(TREM-1)is a member of the immunoglobulin superfamily.It is the main amplifier of the natural immune response and participates in the development and persistence of inflammatory states in the body.Studies have shown that the expression of TREM-1 is up-regulated in early onset severe preeclampsia and may be involved in the differentiation of trophoblast cells,but it remains unknown whether TREM-1 is involved in the pathogenesis of preeclampsia by regulating the release of placental inflammatory factors.Objective To compare the expression differences of TREM-1 and inflammatory factors in placental tissues between PE patients and normal pregnant women,and to reveal the role and mechanism of TREM-1 in the development of PE.Methods 1.The expression and localization of TREM-1 in placental tissues were detected by immunohistochemical staining on placental tissues from 20 PE patients and 20 normal pregnancies,and the expression differences between preeclamptic and normal maternal placental tissues were compared by western blotting and real-time PCR.2.The levels of IL-6,IL-1? and TNF-? m RNA in placenta of two groups were compared by real time-PCR.3.The expression and localization of TREM-1 in TEV-1cells were detected by cellular immunofluorescence.The lipopolysaccharide was used to simulate inflammatory environment in vitro.4.The TREM-1 plasmid and TREM-1-targeted si RNA were constructed and transfected into TEV-1 cells,respectively,to construct trophoblast cell models with overexpression and silencing of TREM-1.LPS stimulation simulated the inflammatory environment.Cells were divided into blank group(without any intervention),the LPS group(untransfected cells,treated with LPS for 24 hours),TREM-1+LPS group(transfected by TREM-1 plasmid,treated with LPS for 24 hours),si TREM-1+LPS group(transfected by si TREM-1,treated with LPS for 24 hours).5.The expressions of TREM-1,p-I?B? and p65 in trophoblasts of four groups were detected by western blotting.6.The m RNA levels of IL-6?IL-8?TNF-? and IL-1? were detected by real time-PCR.Results 1.TREM-1 was expressed in both villous trophoblast cells and extravillous trophoblast cells.Compared with the normal pregnancy group,the protein and m RNA expression of TREM-1 in the placenta of the PE group were increased,and the differences were statistically significant(p <0.05).2.The m RNA levels of IL-6?IL-8?TNF-? and IL-1? in placenta of PE group were significantly higher than those in normal pregnancy group(p <0.05).3.TREM-1 was distributed in the cytoplasm,membrane and nucleus of TEV-1 cells.4.Compared with the blank group,the protein expressions of TREM-1,p-I?B? and intranuclear NF-?B p65 and the m RNA expressions of the inflammatory factors IL-6?IL-8?TNF-? and IL-1? were increased in the LPS group,while the protein expressions of cytoplasmic NF-?B p65 were decreased,and the differences were statistically significant(p <0.05).5.Compared with the LPS group,the protein expression of p-I?B??intranuclear NF-?B p65 and the m RNA expressions of inflammatory factors IL-6?IL-8?TNF-? and IL-1? were increased in the TREM-1+LPS group,while the protein expressions of cytoplasmic NF-?B p65 was decreased;Compared with the LPS group,the protein expressions of p-I?B? ? intranuclear NF-?B p65 and the m RNA expressions of inflammatory factors IL-6?IL-8?TNF-? and IL-1? were decreased in the si TREM-1 +LPS group,while the protein expressions of cytoplasmic NF-?B p65 were decreased,and the differences were statistically significant(p<0.05).Conclusion Our study suggested that TREM-1 was up-regulated in placental tissues of PE patients,and may promote the production of downstream inflammatory factors by activating NF-?B pathway in trophoblast cells,thus playing a pro-inflammatory role and participating in the occurrence and development of PE.