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

The Anti-TNF-alpha Antibody Infliximab Inhibits the Expression of Fat-Transporter-Protein FAT/CD36 in a Selective Hepatic-Radiation Mouse Model
Martius, G.; Cameron, S.; Rave-Fraenk, M.; Hess, C. F.; Wolff, H. A. & Malik, I. A. (2015) 
International Journal of Molecular Sciences16(3) pp. 4682-4697.​

Authors
Martius, Gesa; Cameron, Silke; Rave-Fraenk, Margret; Hess, Clemens Friedrich; Wolff, Hendrik Andreas; Malik, Ihtzaz Ahmed
Issue Date
2015
Type
Journal Article
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-alpha (anti-TNF-alpha) (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-alpha-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-alpha-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-alpha. TNF-alpha-blockage by anti-TNF-alpha 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 alpha-smooth muscle actin (alpha-SMA(+)) cells and F4/80(+) macrophages. In summary, hepatic-radiation triggers fat-accumulation in mice livers, involving acute-phase-processes. Accordingly, anti-TNF-alpha-therapy prevented early radiation-induced expression of FAT/CD36 in vivo.
Publisher
Mdpi Ag
Journal
International Journal of Molecular Sciences 
ISSN
1422-0067
Publication of Göttingen University
Yes
Sponsor
Open-Access-Publikationsfonds 2015
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