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Hepcidin messenger RNA expression in human lymphocytes
Author(s) -
Pinto Jorge P,
Dias Vera,
Zoller Heinz,
Porto Graça,
Carmo Helena,
Carvalho Félix,
De Sousa Maria
Publication year - 2010
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2009.03226.x
Subject(s) - hepcidin , ferroportin , peripheral blood mononuclear cell , biology , messenger rna , intracellular , lymphocyte , microbiology and biotechnology , innate immune system , gene expression , immune system , immunology , inflammation , in vitro , biochemistry , gene
Summary Hepcidin regulates intracellular iron levels by interacting with and promoting the degradation of ferroportin, a membrane protein and the only known cellular iron exporter. Studies of hepcidin expression and regulation have focused on its effects in innate immunity and as a regulator of systemic iron metabolism. In the present study we characterized the expression of hepcidin messenger RNA (mRNA) in human peripheral blood mononuclear cells (PBMCs) with a focus on peripheral blood lymphocytes (PBLs). We found that (1) all human PBMCs analyzed express basal hepcidin mRNA levels; (2) hepcidin mRNA expression increases after T‐lymphocyte activation; (3) expression by PBLs increases in response to challenge by holotransferrin (Fe‐TF) and by ferric citrate in vitro ; (4) the Fe‐TF‐mediated up‐regulation of hepcidin decreases ferroportin expression at the cytoplasmic membrane of PBLs; and (5) silencing of tumour necrosis factor‐α (TNF‐α) abrogates the effect of Fe‐TF. In summary, we show that hepcidin expression determines intracellular iron levels by regulating the expression of ferroportin, as described in other cells, and that inappropriately low expression of hepcidin impairs normal lymphocyte proliferation. The results establish hepcidin as a new player in lymphocyte biology.