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Ferroportin Modulates Macrophage‐Mediated Immune Responses
Author(s) -
Johnson Erin E.,
Murray Megan,
WesslingResnick Marianne
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.692.5
Subject(s) - lipopolysaccharide , ferroportin , macrophage , inflammation , nitric oxide , nitric oxide synthase , chemistry , immune system , iron deficiency , western blot , microbiology and biotechnology , downregulation and upregulation , hepcidin , biology , immunology , biochemistry , medicine , anemia , organic chemistry , gene , in vitro
The iron exporter ferroportin (FPN) plays a key role in iron homeostasis. Infection and inflammation down‐regulate FPN to limit iron efflux from macrophages. Whether FPN contributes to other macrophage immune responses is unknown. In particular, the intersection of iron metabolism and nitric oxide (NO) production by macrophage inducible nitric oxide synthase (iNOS) has been the subject of much debate. Induction of NO synthesis by macrophage iNOS is a key inflammatory response mechanism triggered by cytokines such as INF‐γ, TNF‐α, and IL‐1 and microbial lipopolysaccharide (LPS). While heme iron is required for iNOS dimerization, it remains unclear whether iron increases or decreases NO production. J774 murine macrophages over‐expressing FPN were used to investigate the influence of iron efflux on iNOS activity. When challenged with LPS or Mycobacterium tuberculosis (Mtb), control J774 cells increase NO synthesis as measured by the Greiss reaction. J774 cells over‐expressing FPN have significantly impaired NO induction in response to LPS or Mtb. Western blot analysis shows that increased NO synthesis in control J774 cells is accompanied by increased iNOS expression, but that upregulation of iNOS protein is markedly reduced when J744 cells over‐expressing FPN are challenged with LPS or Mtb. These results suggest that iron efflux by FPN can limit macrophage‐mediated immune responses.