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Hindi Research Article
Heme Activates Macrophage Hepcidin Expression via Toll like Receptor 4 and Extracellular Signal-Regulated Kinases Signaling Pathway
Naveen Kumar Tangudu and Maja Vujić Spasić*Institute of Comparative Molecular Endocrinology, Ulm University, Ulm, Germany
- *Corresponding Author:
- Prof. Dr. Maja Vujić Spasić
Institute of Comparative Molecular Endocrinology
Ulm University, 89081 Ulm, Germany
Tel: +49 731 50 32635
Fax: +49 731 50 32609
E-mail: maja.vujic@uni-ulm.de
Received date: December 21, 2016; Accepted date: January 16, 2017; Published date: January 21, 2017
Citation: Tangudu NK, Vujic Spasic M (2017) Heme Activates Macrophage Hepcidin Expression via Toll like Receptor 4 and Extracellular Signal-Regulated Kinases Signaling Pathway. Clin Pharmacol Biopharm 6:166. doi: 10.4172/2167-065X.1000166
Copyright: © 2017 Tangudu NK, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Tight regulation of systemic and cellular iron levels is required for good health. This control is ensured by hepcidin, a small peptide hormone produced predominantly by the liver. Lack of hepcidin expression or mutations affecting regulators of hepcidin expression, cause common genetic iron disorders. Hepcidin is also expressed in myeloid cells and its expression is increased after infections and in response to lipopolysaccharide. Our study uncovers that macrophages rapidly increase hepcidin expression in response to excess of heme. Moreover, we demonstrate that the underlying mechanism by which heme triggers hepcidin activation in macrophages depends on the Toll Like Receptor (TLR)-4 and the contribution of Extracellular Signal-Regulated Kinases (ERK) pathway. Our data propose the contribution of hepcidin, locally produced by macrophages, to the pathology of disorders characterized by excess of free heme, such as certain bacterial infections and hemolytic disorders. Finally, using macrophages from Hfe-deficient mice, we demonstrate that the lack of Hfe is not critical for the hepcidin induction by heme but is required to maintain basal hepcidin expression in macrophages. The findings that the levels of hepcidin in macrophages are directly controlled by the actions of Hfe in these cells expand our view on Hfe beyond the liver and as mere regulator of iron levels.
