Distinct requirements for Hfe in basal and induced hepcidin levels in iron overload and inflammation

• DOI: 10.1152/ajpgi.00092.2006
• Publication Date: 2006-03-25T01:45:08Z
• Authors: Marco Constante; Wenlei Jiang; Dongmei Wang; Valérie-Ann Raymond; Marc Bilodeau; Manuela M. Santos
• Keywords: Hereditary hemochromatosis; Basal (medicine); Ferroportin

Hepcidin is a negative regulator of iron absorption produced mainly by the liver in response to changes stores and inflammation, its levels have been shown regulate intestinal basolateral transporter ferroportin1 (Fp1). Hereditary hemochromatosis patients Hfe-deficient mice show inappropriate expression hepcidin but, apparent contradiction, still retain ability alterations metabolism. To further understand molecular relationships among Hfe, hepcidin, Fp1, we investigated Fp1 regulation (Hfe-/- beta2m-/-) deprivation, loading, acute inflammation. We found that whereas basal were manifestly dependent on presence Hfe mouse background, all able situations altered homeostasis. In liver, was modulated opposite directions LPS, similar observed wild-type mice. addition, iron-deprived mount robust after LPS challenge Toll-like receptor 4 (TLR-4)-deficient fail LPS. conclusion, these results suggest although necessary for establishment levels, it dispensable through both iron-sensing inflammatory pathways, hepatic largely independent Hfe. The pathway overrides TLR-4 dependent.