Cirrhosis and Liver Failure
Systemic and local expression levels of TNF-like ligand 1A and its decoy receptor 3 are increased in primary biliary cirrhosis
Article first published online: 9 SEP 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 34, Issue 5, pages 679–688, May 2014
How to Cite
Liver Int. 2014: 34: 679–688
- Issue published online: 8 APR 2014
- Article first published online: 9 SEP 2013
- Accepted manuscript online: 2 AUG 2013 07:56AM EST
- Manuscript Accepted: 24 JUL 2013
- Manuscript Received: 15 FEB 2013
- Japan Society for the Promotion of Science. Grant Number: #25860576
- National Hospital Organization
- Ministry of Health, Labour and Welfare of Japan
- decoy receptor 3;
- primary biliary cirrhosis;
- tumour necrosis factor-like ligand 1A;
- ursodeoxycholic acid
Background & Aims
Through a genome-wide association study of a Japanese population, we recently identified TNFSF15, a gene encoding TNF-like ligand 1A (TL1A), as a susceptibility gene for primary biliary cirrhosis (PBC). We investigated the clinical significance of TL1A and one of its receptors, decoy receptor 3 (DcR3), in PBC.
We analysed the systemic and local expression of TL1A and DcR3 in 110 PBC patients and 46 healthy controls using enzyme-linked immunosorbent assay, quantitative polymerase chain reaction and immunohistochemical staining.
Serum TL1A levels were significantly increased in PBC patients at both early and late stages as compared with healthy controls, and its levels were significantly decreased in early-stage PBC patients after ursodeoxycholic acid (UDCA) treatment. TL1A was immunohistochemically localized to biliary epithelial cells, Kupffer cells, blood vessels and infiltrating mononuclear cells in the PBC liver. In addition, TL1A messenger RNA expression was increased in the PBC liver as compared with the non-diseased liver. Serum DcR3 levels were also significantly increased in PBC patients, and were significantly decreased after UDCA treatment in early-stage PBC patients.
These results indicate that TL1A and DcR3 may play an important role in the pathogenesis of PBC.