Role of SOCS3 in the Jak/stat3 pathway in the human placenta: different mechanisms for preterm and term labor

Acta Obstet Gynecol Scand. 2015 Oct;94(10):1112-7. doi: 10.1111/aogs.12708. Epub 2015 Aug 20.

Abstract

Introduction: To identify changes in interleukin (IL)-6 levels and its pathway (Jak/stat3) in the human placenta during preterm and term labor, placental tissues were collected from primiparous women who underwent vaginal deliveries or cesarean sections in our hospital. The women were divided into three groups: preterm labor (n = 15), term labor (n = 15), and term not in labor (n = 15).

Material and methods: IL-6 levels were detected by ELISA in placental supernatant, and p-STAT3 and SOCS3 protein was detected by Western blot. TUNEL was used to detect apoptosis in trophoblasts. HTR-8/SVneo cells were cultured after stimulation with IL-6, and we measured p-STAT3, SOCS3, and the rate of apoptosis.

Results: Expression of p-STAT3 and SOCS3 in the placenta and trophoblast cells showed that IL-6 levels were highest in the preterm labor group and lowest in the term not in labor group. The highest expression of placental SOCS3 protein was observed in the preterm labor group. More apoptotic cells were found in the preterm labor group than in the other two groups by TUNEL. SOCS3 and p-STAT3 expression was significantly upregulated after stimulation by IL-6 in trophoblast cells in a dose-dependent manner. However, p-STAT3 was significantly decreased after 50 ng/mL and 100 ng/mL IL-6 for 72 h. A significant increase of apoptosis was observed with treatment of 50 ng/mL IL-6 in HTR-8/SVneo cells.

Conclusions: The role of the SOCS3 protein in the Jak/stat3 pathway is to mediate different mechanisms for preterm and term labor processes in the placenta.

Keywords: Interleukin-6; Jak/stat3 pathway; inflammation; placenta; preterm labor; term labor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis / physiology
  • Blotting, Western
  • Female
  • Flow Cytometry
  • Humans
  • In Situ Nick-End Labeling
  • Interleukin-6 / analysis
  • Janus Kinases / physiology*
  • Labor, Obstetric / physiology*
  • Obstetric Labor, Premature / physiopathology*
  • Placenta / physiology*
  • Placenta / physiopathology
  • Pregnancy
  • STAT3 Transcription Factor / physiology*
  • Signal Transduction / physiology*
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / physiology*
  • Up-Regulation / physiology
  • Young Adult

Substances

  • Interleukin-6
  • SOCS3 protein, human
  • STAT3 Transcription Factor
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Janus Kinases