Hypoferraemia during the early inflammatory response is dependent on tumour necrosis factor activity in a murine model of protracted peritonitis

Schubert, Thomas E. O. and Bosserhoff, Anja K. and Peyssonnaux, Carole and Echtenacher, Bernd and Knutson, Mitchell and Hofstaedter, Ferdinand and Maennel, Daniela N. (2012) Hypoferraemia during the early inflammatory response is dependent on tumour necrosis factor activity in a murine model of protracted peritonitis. MOLECULAR MEDICINE REPORTS, 6 (4). pp. 838-842. ISSN 1791-2997, 1791-3004

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Abstract

On the grounds of clinical,in vitro and in vivo studies, tumour necrosis factor (TNF) is considered to be one of the inflammatory cytokines that contributes to to the generation of hypoferraemia and anaemia of inflammation (AI). We used a recently described murine model for AI and hypoferraemia, based on sublethal caecal ligation and puncture (CLP) with ensuing protracted peritonitis, to investigate the contribution of TNF to the generation of hypoferraemia. During the early inflammatory response to CLP, a marked decrease in serum iron concentration occurs within 8 h. To determine whether TNF contributes to the generation of hypoferraemia at this time point, we studied TNF-deficient mice and wild-type mice that underwent CLP. The serum iron concentration was decreased in wild-type mice whereas TNF-deficient mice maintained normal serum iron levels following CLP. Hypoferraemia in wild-type Mice was accompanied by the downregulation of ferroportin 1 (Fpl) in macrophages. In the macrophages of TNF-deficient mice, Fpl was not downregulated following. CLP. The initial expression of hepcidin was detectable at the mRNA level but not at the protein level by immunohistochemistry in wild-type and TNF-deficient mice. Therefore, hepcidin does not appear to be involved in the regulation of early h,hypoferraemia. TNF appears to regulate the expression of Fpl by transcriptional control. Our results demonstrate that TNF mediates hypoferraemia during the early inflammatory response by regulating the expression of Fpl in macrophages.

Item Type: Article
Uncontrolled Keywords: FACTOR-ALPHA; SEPTIC-PERITONITIS; IRON SEQUESTRATION; INTERFERON-GAMMA; CHRONIC-DISEASE; MOUSE MODEL; HEPCIDIN; ANEMIA; FERROPORTIN; CELLS; hypoferraemia; blood; TNF; mouse; septic peritonitis
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Immunologie
Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 06 May 2020 04:44
Last Modified: 06 May 2020 04:44
URI: https://pred.uni-regensburg.de/id/eprint/18057

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