Severe iron deficiency blunts the response of the iron regulatory gene Hamp and pro-inflammatory cytokines to lipopolysaccharide

Darshan, Deepak, Frazer, David M., Wilkins, Sarah J. and Anderson, Gregory J. (2010) Severe iron deficiency blunts the response of the iron regulatory gene Hamp and pro-inflammatory cytokines to lipopolysaccharide. Haematologica - The Haematology Journal, 95 10: 1660-1667. doi:10.3324/haematol.2010.022426

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Author Darshan, Deepak
Frazer, David M.
Wilkins, Sarah J.
Anderson, Gregory J.
Title Severe iron deficiency blunts the response of the iron regulatory gene Hamp and pro-inflammatory cytokines to lipopolysaccharide
Formatted title
Severe iron deficiency blunts the response of the iron regulatory gene Hamp and pro-inflammatory cytokines to lipopolysaccharide
Journal name Haematologica - The Haematology Journal   Check publisher's open access policy
ISSN 0390-6078
1592-8721
Publication date 2010-10-01
Sub-type Article (original research)
DOI 10.3324/haematol.2010.022426
Open Access Status DOI
Volume 95
Issue 10
Start page 1660
End page 1667
Total pages 9
Place of publication Pavia, PV, Italy
Publisher Fondazione Ferrata Storti
Collection year 2011
Language eng
Formatted abstract
Background: Expression of the key iron regulatory hormone hepcidin is increased by some stimuli (iron loading, inflammation) but decreased by others (increased erythropoiesis, iron deficiency). We investigated the response of hepcidin to increased erythropoiesis and iron deficiency in the presence of an acute inflammation to assess the relative strengths of these stimuli.

Design and Methods: Sprague-Dawley rats were maintained on control or iron-deficient diets and treated with lipopolysaccharide to induce inflammation or phenylhydrazine to stimulate erythropoiesis. The levels of Hamp, IL-6 and α2m mRNA were determined by qualitative real-time polymerase chain reaction and those of serum interleukin-6 and tumor necrosis factor-α were measured by enzyme-linked immunosorbent assay. Cultured RAW264.7 and HuH7 cells were used in associated studies.

Results: The increase in hepatic hepcidin levels induced by lipopolysaccharide was not affected by phenylhydrazine treatment but was blunted by iron deficiency. Lipopolysaccharide-treated iron-deficient animals also showed lower liver α2m mRNA and reduced serum interleukin-6 and tumor necrosis factor-α, suggesting a more generalized effect of iron deficiency. Similarly, RAW 264.7 cells treated with iron chelators and then stimulated with lipopolysaccharide showed lower IL-6 mRNA than cells treated with lipopolysaccharide alone. Huh7 cells treated with an iron chelator showed a blunted hepcidin response to interleukin-6, suggesting that the response of hepatic parenchymal cells to inflammatory cytokines may also be iron-dependent.

Conclusions: In any one physiological situation, net hepcidin levels are determined by the relative strengths of competing stimuli. The ability of severe iron deficiency to blunt the response to lipopolysaccharide of both hepcidin and other markers of inflammation suggests that adequate iron levels are necessary for a full acute phase response.
©2010 Ferrata Storti Foundation. This is an open-access paper.
Keyword Hepcidin
α2m
alpha2m
Alpha2-macroglobulin
Erythropoiesis
Iron
Inflammation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
 
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