Expression of suppressor of cytokine signaling 3 and its significance in human placenta with pregnant intrahepatic cholestasis

Abstract

To detect the expression and significance of suppressor of cytokine signaling 3(SOCS3) in the placentas of pregnant women with intrahepatic cholestasis of pregnancy (ICP). Totally, 44 ICP gravidas, including 21 severe ICP and 23 mild ICP who delivered through cesarean section at the Second Xiangya Hospital of Central South University from April 2008 to January 2009, were selected as the ICP group, and another 25 healthy pregnant women were chosen as control. Placentas of the above gravidas were collected and the expression and localization of SOCS3 were determined by immunohistochemical peroxidase streptomyces-avidin link (SP) method (indicated by the percentage of positive cells and average gray scale) and the levels of interleukin-10 (IL-10) and interferon-γ (IFN-γ) from placenta homogenation were measured by enzyme linked immunoadsorbent assay (ELISA). (1) SOCS3 were expressed in placentas of both groups mainly in the intracytoplasma of trophocyte. However, weakly positive, positive, and strongly positive expressions were found in the severe ICP, mild ICP and the control group, respectively. Almost no expression was detected in membrane and nucleus of the trophoblasts. (2) The percentage of SOCS3 positive cells in the severe ICP group was significantly lower than in the control and the mild ICP group, respectively [(0.15 ± 0.08) % vs (0.69 ± 0.12) % and (0.42 ± 0.09) %, P < 0.01]. The average gay SOCS3 in placental tissue in the severe ICP group was significantly higher than that in control and mild ICP group, respectively (204 ± 7 vs 81 ± 7 and 147 ± 7, P < 0.01). (3) Significant lower level of IL-10 in placenta homogenation was found in the severe ICP group than in the control and mild ICP group [(1.16 ± 0.68) µg/L, vs (1.39 ± 0.08) µg/L and (1.22 ± 0.75) µg/L, P < 0.01]. (4) The opposite results were found in the level of IFN-γ in trophoblasts and the ratio of IFN-γ/IL-10 [severe ICP group: (16.8 ± 0.7) µg/L and 16.02 ± 2.79; control group: (10.5 ± 0.3) µg/L and 8.56 ± 0.14; mild ICP group: (13.4 ± 0.5) µg/L and 8.56 ± 0.14, P < 0.01]. (5) Negative correlation was shown between the percentage of SOCS3 positive cells in trophoblasts and the ratio of IFN-γ/IL-10 (r = -0.685 and -0.702, P < 0.01), and the average gay SOCS3 was positively correlated with the ratio of IFN-γ/IL-10 (r = 0.621 and 0.891, P < 0.01) in both mild and severe ICP group. SOCS3 may participate in the pathogenesis of ICP and its expression may affected by the severity of ICP, and SOCS3 may also play a role in the immunological regulation in ICP patients.