IL-17A up-regulates expression of endothelial tissue factor in liver cirrhosis via the ROS/p38 signal pathway

Biochem Biophys Res Commun. 2016 Jan 29;470(1):41-47. doi: 10.1016/j.bbrc.2015.12.093. Epub 2015 Dec 29.

Abstract

Interleukin-17A (IL-17A), an inflammatory cytokine, is elevated in liver cirrhosis. Inflammation and coagulation dysfunction are closely related. Tissue factor (TF) is a bridge between endothelial activation, blood coagulation and inflammation. The aims of the present study were to evaluate endothelial TF expression in liver cirrhosis and identify the possible underlying role of IL-17A in TF expression. In the present study, we found that TF expression was increased on endothelium of splenic vein from cirrhotic patients and significantly correlated with intima/media ratios of splenic vein and coagulation parameters. Serum levels of IL-17A were significantly higher in cirrhotic patients as compared with normal controls. Cirrhotic serum and IL-17A stimulated TF expression in HUVECs, which was reduced by blockade of IL-17A, p38, and reactive oxygen species (ROS). Taken together, our data show that enhanced expression of endothelial TF, which plays an important role in coagulopathy and splenic vein remodeling in liver cirrhosis, is induced by IL-17A in a ROS dependent manner.

Keywords: Endothelial cells; Interleukin-17; Liver cirrhosis; Reactive oxygen species; Tissue factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endothelium, Vascular / metabolism*
  • Gene Expression Regulation
  • Humans
  • Interleukin-17 / metabolism*
  • Liver Cirrhosis / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction
  • Splenic Vein / metabolism*
  • Thromboplastin / metabolism*
  • Up-Regulation
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • IL17A protein, human
  • Interleukin-17
  • Reactive Oxygen Species
  • Thromboplastin
  • p38 Mitogen-Activated Protein Kinases