8th Annual BMRP Investigator Meeting - Abstract
Manipulating Iron Metabolism to Control Intestinal Inflammation
Lijian Wang1,2, Estela Trebicka1, Hai Ning Shi1, Charles C. Hong3, Herbert Y. Lin4, Jodie L. Babitt4 and Bobby J. Cherayil1,a
1Mucosal Immunology Laboratory, Massachusetts General Hospital and Harvard Medical School; 2Department of Nutrition, Harvard School of Public Health (Boston, Massachusetts, U.S.A.); 3Division of Cardiovascular Medicine, Vanderbilt University School of Medicine (Nashville, Tennessee, U.S.A.); 4Division of Nephrology, Massachusetts General Hospital (Boston, U.S.A.)
Hepcidin is a peptide secreted by the liver that functions as a central regulator of iron homeostasis. Our preliminary studies have shown that hepcidin also influences macrophage innnate immune responses as a result of changes in intracellular iron concentrations: low hepcidin decreases pro-inflammatory cytokine production while elevated hepcidin has the opposite effect. Since chronic inflammatory states such as IBD are associated with an increase in circulating hepcidin and disordered iron metabolism, we hypothesized that inhibiting hepcidin expression would restore normal iron homeostasis and reduce the severity of intestinal inflammation. We tested this idea using the piroxicam/IL-10 knock-out mouse model of colitis and found that reagents that blocked hepcidin production also reduced the severity of intestinal inflammation in this model. These results provide the foundation for a novel anti-inflammatory strategy based on manipulating iron metabolism.
aPrincipal Investigator