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Int. J. Mol. Sci. 2015, 16(3), 4682-4697; doi:10.3390/ijms16034682

The Anti-TNF-α Antibody Infliximab Inhibits the Expression of Fat-Transporter-Protein FAT/CD36 in a Selective Hepatic-Radiation Mouse Model

1
Department of Gastroenterology and Endocrinology, University Medical Center Goettingen, Robert-Koch-Strasse 40, Goettingen 37075, Niedersachsen, Germany
2
Department of Radiotherapy and Radiooncology, University Medical Center Goettingen, Robert-Koch-Strasse 40, Goettingen 37075, Niedersachsen, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Bing Yan
Received: 3 January 2015 / Revised: 5 February 2015 / Accepted: 13 February 2015 / Published: 2 March 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Previously, we reported a radiation-induced inflammation triggering fat-accumulation through fatty-acid-translocase/cluster of differentiation protein 36 (FAT/CD36) in rat liver. Furthermore, inhibition of radiation-induced FAT/CD36-expression by anti-tumor necrosis factor-α (anti-TNF-α) (infliximab) was shown in vitro. The current study investigates fat-accumulation in a mouse-model of single-dose liver-irradiation (25-Gray) and the effect of anti-TNF-α-therapy on FAT/CD36 gene-expression. Mice livers were selectively irradiated in vivo in presence or absence of infliximab. Serum- and hepatic-triglycerides, mRNA, and protein were analyzed by colorimetric assays, RT-PCR, Immunofluorescence and Western-Blot, respectively. Sudan-staining was used demonstrating fat-accumulation in tissue. In mice livers, early (1–3 h) induction of TNF-α-expression, a pro-inflammatory cytokine, was observed. It was followed by elevated hepatic-triglyceride level (6–12 h), compared to sham-irradiated controls. In contrast, serum-triglyceride level was decreased at these time points. Similar to triglyceride level in mice livers, Sudan staining of liver cryosections showed a quick (6–12 h) increase of fat-droplets after irradiation. Furthermore, expression of fat-transporter-protein FAT/CD36 was increased at protein level caused by radiation or TNF-α. TNF-α-blockage by anti-TNF-α showed an early inhibition of radiation-induced FAT/CD36 expression in mice livers. Immunohistochemistry showed basolateral and cytoplasmic expression of FAT/CD36 in hepatocytes. Moreover, co-localization of FAT/CD36 was detected with α-smooth muscle actin (α-SMA+) cells and F4/80+ macrophages. In summary, hepatic-radiation triggers fat-accumulation in mice livers, involving acute-phase-processes. Accordingly, anti-TNF-α-therapy prevented early radiation-induced expression of FAT/CD36 in vivo. View Full-Text
Keywords: irradiation; fat accumulation; liver; FAT/CD36; TNF-α; infliximab irradiation; fat accumulation; liver; FAT/CD36; TNF-α; infliximab
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Martius, G.; Cameron, S.; Rave-Fränk, M.; Hess, C.F.; Wolff, H.A.; Malik, I.A. The Anti-TNF-α Antibody Infliximab Inhibits the Expression of Fat-Transporter-Protein FAT/CD36 in a Selective Hepatic-Radiation Mouse Model. Int. J. Mol. Sci. 2015, 16, 4682-4697.

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