BioSpace Collaborative

Academic/Biomedical Research
News & Jobs
Biotechnology and Pharmaceutical Channel Medical Device and Diagnostics Channel Clinical Research Channel BioSpace Collaborative    Job Seekers:  Register | Login          Employers:  Register | Login  

NEWSLETTERS
Free Newsletters
Archive
My Subscriptions

NEWS
News by Subject
News by Disease
News by Date
PLoS
Search News
Post Your News
JoVE

CAREER NETWORK
Job Seeker Login
Most Recent Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers

HOTBEDS
Regional News
US & Canada
  Biotech Bay
  Biotech Beach
  Genetown
  Pharm Country
  BioCapital
  BioMidwest
  Bio NC
  BioForest
  Southern Pharm
  BioCanada East
  US Device
Europe
Asia

DIVERSITY

PROFILES
Company Profiles

INTELLIGENCE
Research Store

INDUSTRY EVENTS
Research Events
Post an Event
RESOURCES
Real Estate
Business Opportunities

PLoS By Category | Recent PLoS Articles
Gastroenterology and Hepatology - Hematology - Immunology - Molecular Biology

Tumor Necrosis Factor a Inhibits Expression of the Iron Regulating Hormone Hepcidin in Murine Models of Innate Colitis
Published: Thursday, May 31, 2012
Author: Nanda Kumar N. Shanmugam et al.

by Nanda Kumar N. Shanmugam, Shiri Ellenbogen, Estela Trebicka, Lijian Wang, Subhankar Mukhopadhyay, Adam Lacy-Hulbert, Carey Ann Gallini, Wendy S. Garrett, Bobby J. Cherayil

Background

Abnormal expression of the liver peptide hormone hepcidin, a key regulator of iron homeostasis, contributes to the pathogenesis of anemia in conditions such as inflammatory bowel disease (IBD). Since little is known about the mechanisms that control hepcidin expression during states of intestinal inflammation, we sought to shed light on this issue using mouse models.

Methodology/Principal Findings

Hepcidin expression was evaluated in two types of intestinal inflammation caused by innate immune activation—dextran sulfate sodium (DSS)-induced colitis in wild-type mice and the spontaneous colitis occurring in T-bet/Rag2-deficient (TRUC) mice. The role of tumor necrosis factor (TNF) a was investigated by in vivo neutralization, and by treatment of a hepatocyte cell line, as well as mice, with the recombinant cytokine. Expression and activation of Smad1, a positive regulator of hepcidin transcription, were assessed during colitis and following administration or neutralization of TNFa. Hepcidin expression progressively decreased with time during DSS colitis, correlating with changes in systemic iron distribution. TNFa inhibited hepcidin expression in cultured hepatocytes and non-colitic mice, while TNFa neutralization during DSS colitis increased it. Similar results were obtained in TRUC mice. These effects involved a TNFa-dependent decrease in Smad1 protein but not mRNA.

Conclusions/Significance

TNFa inhibits hepcidin expression in two distinct types of innate colitis, with down-regulation of Smad1 protein playing an important role in this process. This inhibitory effect of TNFa may be superseded by other factors in the context of T cell-mediated colitis given that in the latter form of intestinal inflammation hepcidin is usually up-regulated.

  More...

 

//-->