Cytokines are implicated in the anaemia of chronic disease by reducing erythropoiesis and increasing iron sequestration in the reticuloendotheial system. However, the effect of cytokines, in particular TNFα (tumour necrosis factor α), on small bowel iron uptake and iron-transporter expression remains unclear. In the present study, we subjected CD1 male mice to intraperitoneal injection with TNFα (10 ng/mouse) and then examined the expression and localization of DMT1 (divalent metal transporter 1), IREG1 (iron-regulated protein 1) and ferritin in duodenum. Liver and spleen samples were used to determine hepcidin mRNA expression. Changes in serum iron and iron loading of duodenum, spleen and liver were also determined. We found a significant (P<0.05) fall in serum iron 3 h post-TNFα exposure. This was coincident with increased iron deposition in the spleen. After 24 h of exposure, there was a significant decrease in duodenal iron transfer (P<0.05) coincident with increased enterocyte ferritin expression (P<0.05) and re-localization of IREG1 from the basolateral enterocyte membrane. Hepatic hepcidin mRNA levels remained unchanged, whereas splenic hepcidin mRNA expression was reduced at 24 h. In conclusion, we provide evidence that TNFα may contribute to anaemia of chronic disease by iron sequestration in the spleen and by reduced duodenal iron transfer, which seems to be due to increased enterocyte iron binding by ferritin and a loss of IREG1 function. These observations were independent of hepcidin mRNA levels.
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Research Article|
June 14 2006
Tumour necrosis factor α causes hypoferraemia and reduced intestinal iron absorption in mice
Abas H. Laftah
;
Abas H. Laftah
*Division of Medical Sciences, University of Birmingham, Birmingham B15 2TT, U.K.
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Naveen Sharma
;
Naveen Sharma
*Division of Medical Sciences, University of Birmingham, Birmingham B15 2TT, U.K.
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Matthew J. Brookes
;
Matthew J. Brookes
*Division of Medical Sciences, University of Birmingham, Birmingham B15 2TT, U.K.
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Andrew T. McKie
;
Andrew T. McKie
†Nutrition Research Division, King's College London, London SE1 9NH, U.K.
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Robert J. Simpson
;
Robert J. Simpson
†Nutrition Research Division, King's College London, London SE1 9NH, U.K.
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Tariq H. Iqbal
;
Tariq H. Iqbal
1
‡Gastroenterology Unit, Walsgrave Hospital, Clifford Bridge Road, Coventry CV2 2DX, U.K.
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Chris Tselepis
*Division of Medical Sciences, University of Birmingham, Birmingham B15 2TT, U.K.
2To whom correspondence should be addressed (email c.tselepis@bham.ac.uk).
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Biochem J (2006) 397 (1): 61–67.
Article history
Received:
February 06 2006
Revision Received:
March 24 2006
Accepted:
March 27 2006
Accepted Manuscript online:
March 27 2006
Citation
Abas H. Laftah, Naveen Sharma, Matthew J. Brookes, Andrew T. McKie, Robert J. Simpson, Tariq H. Iqbal, Chris Tselepis; Tumour necrosis factor α causes hypoferraemia and reduced intestinal iron absorption in mice. Biochem J 1 July 2006; 397 (1): 61–67. doi: https://doi.org/10.1042/BJ20060215
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