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Pentoxifylline attenuates methionine- and choline-deficient-diet-induced steatohepatitis by suppressing TNF-α expression and endoplasmic reticulum stress.

Authors
 Min Kyung Chae  ;  Sang Gyu Park  ;  Sun-Ok Song  ;  Eun Seok Kang  ;  Bong Soo Cha  ;  Hyun Chul Lee  ;  Byung-Wan Lee 
Citation
 Experimental Diabetes Research, Vol.2012 : 762565, 2012 
Journal Title
 Experimental Diabetes Research 
ISSN
 1687-5214 
Issue Date
2012
Abstract
BACKGROUND: Pentoxifylline (PTX) anti-TNF properties are known to exert hepatoprotective effects in various liver injury models. The aim of this study was to investigate whether PTX has beneficial roles in the development of methionine- and choline-deficient-(MCD-) diet-induced NAFLD SD rats in vivo and TNF-α-induced Hep3B cells in vitro. METHODS: SD Rats were classified according to diet (chow or MCD diet) and treatment (normal saline or PTX injection) over a period of 4 weeks: group I (chow + saline, n = 4), group II (chow + PTX), group III (MCD + saline), and group IV (MCD + PTX). Hep3B cells were treated with 100 ng/ml TNF-α (24 h) in the absence or presence of PTX (1 mM). RESULTS: PTX attenuated MCD-diet-induced serum ALT levels and hepatic steatosis. In real-time PCR and western blotting analysis, PTX decreased MCD-diet-induced TNF-alpha mRNA expression and proapoptotic unfolded protein response by ER stress (GRP78, p-eIF2, ATF4, IRE1α, CHOP, and p-JNK activation) in vivo. PTX (1 mM) reduced TNF-α-induced activation of GRP78, p-eIF2, ATF4, IRE1α, and CHOP in vitro. CONCLUSION: PTX has beneficial roles in the development of MCD-diet-induced steatohepatitis through partial suppression of TNF-α and ER stress.
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DOI
10.1155/2012/762565
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
강은석(Kang, Eun Seok) ORCID logo https://orcid.org/0000-0002-0364-4675
송선옥(Song, Sun Ok)
이병완(Lee, Byung Wan) ORCID logo https://orcid.org/0000-0002-9899-4992
이현철(Lee, Hyun Chul)
차봉수(Cha, Bong Soo) ORCID logo https://orcid.org/0000-0003-0542-2854
채민경(Chae, Min Kyung)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90278
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