Expression Of IL-18and Caspase-1in Syncytiotrophoblast Of Intrahepatic Cholestasis Of Pregnancy

Objective To evaluate the expression and location of theIL-18,caspase-1and the activity of caspase-1in human placentasyncytiotrophoblast and explore the relationship between IL-18andcaspase-1in intrahepatic cholestasis of pregnancy（ICP）．Methods Forty women with ICP who delivered from March2011to November2011in the First Affiliated Hospital of Chongqing MedicalUniversity were chosen as the study objects．They were classified into mildgroup (n=20), severe group (n=20) and elective term cesarean sectionsgroup without previous onset of labor and perinatal complications (controlgroup，n=20)．Serum IL-18was examined by ELISA. Using automaticbiochemical analysis instrument to examine the serum alanineaminotransferase (ALT) and aspartate aminotransferase(AST). Placentaswere collected after they delivered and immunohistochemicalstreptravidin-biotin pemxidase (SP) method was used to detect theexpression and localization of IL-18and caspase-1protein. Western blot analysis was used to quantify IL-18and caspase-1protein expressionlevel．Activation of caspase-1was measured by colorimetric assay．Results (1) The IL-18,ALT,AST level in serum of the severe andmild groups were78.98±1.75,280.7±18.17,175.65±19.78and50.79±1.41,95.05±19.73,61.55±14.54, respectively, compared with mild group, IL-18serum level was higher in severe group (P<0.05); they were significantlyhigher than that in control group (44.02±1.01,26.8±5.67,26.35±4.83,P<0.05)．(2) IL-18was located in the placenta syncytiotrophoblastic cellsof control group and mild ICP group, stained light tan and mostly in thecytoplasm; in severe ICP group, IL-18was also located in placentasyncytiotrophoblastic cell mainly in the cytoplasm with dark tan staining.Caspase-1was located in the placenta syncytiotrophoblastic cells of controlgroup and mild ICP group, stained light tan and mostly in the cellmembrane; in severe ICP group, caspase-1was also located in placentasyncytiotrophoblastic cell mainly in the cell membrane and cytoplasm withdark tan staining.(3) The IL-18protein level in placentasyncytiotrophoblast of the severe and mild groups was0.66±0.03and0.39±0.05, respectively, compared with mild group, IL-18protein levelwas higher in severe group (P<0.05); they were significantly higher thanthat in control group (0.10±0.06, P<0.05)．The caspase-1protein level inplacenta syncytiotrophoblast of the severe and mild groups was1.16±0.08and0.94±0.11, respectively, compared with mild group, caspase-1protein level was higher in severe group (P<0.05); they were significantly higherthan that in control group (0.31±0.15, P<0.05)．(4) The enzymatic activityof caspase-1in placenta syncytiotrophoblast of the severe and mild groupswas0.80±0.07and0.44±0.03, respectively, compared with mild group,activity of caspase-1was higher in severe group (P<0.05); they weresignificantly higher than that in control group (0.19±0.06, P<0.05)．Conclusions The maternal immune abnormalities mediated by IL-18and caspase-1signaling pathways may participate in the pathogenesis ofhepatic damage process in ICP.