title: Hepcidin regulation by BMP signaling in macrophages is lipopolysaccharide dependent.
abstract: Hepcidin is an antimicrobial peptide, which also negatively regulates iron in circulation by controlling iron absorption from dietary sources and iron release from macrophages. Hepcidin is synthesized mainly in the liver, where hepcidin is regulated by iron loading, inflammation and hypoxia. Recently, we have demonstrated that bone morphogenetic protein (BMP)-hemojuvelin (HJV)-SMAD signaling is central for hepcidin regulation in hepatocytes. Hepcidin is also expressed by macrophages. Studies have shown that hepcidin expression by macrophages increases following bacterial infection, and that hepcidin decreases iron release from macrophages in an autocrine and/or paracrine manner. Although previous studies have shown that lipopolysaccharide (LPS) can induce hepcidin expression in macrophages, whether hepcidin is also regulated by BMPs in macrophages is still unknown. Therefore, we examined the effects of BMP signaling on hepcidin expression in RAW 264.7 and J774 macrophage cell lines, and in primary peritoneal macrophages. We found that BMP4 or BMP6 alone did not have any effect on hepcidin expression in macrophages although they stimulated Smad1/5/8 phosphorylation and Id1 expression. In the presence of LPS, however, BMP4 and BMP6 were able to stimulate hepcidin expression in macrophages, and this stimulation was abolished by the NF-κB inhibitor Ro1069920. These results suggest that hepcidin expression is regulated differently in macrophages than in hepatocytes, and that BMPs regulate hepcidin expression in macrophages in a LPS-NF-κB dependent manner.
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Xinggang
authors.initials: X
authors.lastname: Wu
authors.forename: Lai-Ming
authors.initials: LM
authors.lastname: Yung
authors.forename: Wai-Hang
authors.initials: WH
authors.lastname: Cheng
authors.forename: Paul B
authors.initials: PB
authors.lastname: Yu
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Babitt
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Lin
authors.forename: Yin
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D015153:Blotting, Western; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology; D055418:Bone Morphogenetic Protein 6 / Q000494:pharmacology; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D064451:Hepcidins; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051898:Smad1 Protein / Q000378:metabolism; D051902:Smad5 Protein / Q000378:metabolism; D051904:Smad8 Protein / Q000378:metabolism; D013454:Sulfoxides / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D023181:Antimicrobial Cationic Peptides; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; C579599:Hamp protein, mouse; D064451:Hepcidins; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D008070:Lipopolysaccharides; D016328:NF-kappa B; C461648:Ro 106-9920; D051898:Smad1 Protein; D051902:Smad5 Protein; D051904:Smad8 Protein; D013454:Sulfoxides; D013777:Tetrazoles