Academic Journal
Tumour necrosis factor {alpha} signalling through activation of Kupffer cells plays an essential role in liver fibrosis of non-alcoholic steatohepatitis in mice
| العنوان: | Tumour necrosis factor {alpha} signalling through activation of Kupffer cells plays an essential role in liver fibrosis of non-alcoholic steatohepatitis in mice |
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| المؤلفون: | Tomita, K, Tamiya, G, Ando, S, Ohsumi, K, Chiyo, T, Mizutani, A, Kitamura, N, Toda, K, Kaneko, T, Horie, Y, Han, J-Y, Kato, S, Shimoda, M, Oike, Y, Tomizawa, M, Makino, S, Ohkura, T, Saito, H, Kumagai, N, Nagata, H, Ishii, H, Hibi, T |
| بيانات النشر: | BMJ Publishing Group Ltd |
| سنة النشر: | 2006 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | Liver fibrosis |
| الوصف: | Background: While tumour necrosis factor α (TNF-α) appears to be associated with the development of non-alcoholic steatohepatitis (NASH), its precise role in the pathogenesis of NASH is not well understood. Methods: Male mice deficient in both TNF receptors 1 (TNFR1) and 2 (TNFR2) (TNFRDKO mice) and wild-type mice were fed a methionine and choline deficient (MCD) diet or a control diet for eight weeks, maintaining isoenergetic intake. Results: MCD dietary feeding of TNFRDKO mice for eight weeks resulted in attenuated liver steatosis and fibrosis compared with control wild-type mice. In the liver, the number of activated hepatic Kupffer cells recruited was significantly decreased in TNFRDKO mice after MCD dietary feeding. In addition, hepatic induction of TNF-α, vascular cell adhesion molecule 1, and intracellular adhesion molecule 1 was significantly suppressed in TNFRDKO mice. While in control animals MCD dietary feeding dramatically increased mRNA expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) in both whole liver and hepatic stellate cells, concomitant with enhanced activation of hepatic stellate cells, both factors were significantly lower in TNFRDKO mice. In primary cultures, TNF-α administration enhanced TIMP-1 mRNA expression in activated hepatic stellate cells and suppressed apoptotic induction in activated hepatic stellate cells. Inhibition of TNF induced TIMP-1 upregulation by TIMP-1 specific siRNA reversed the apoptotic suppression seen in hepatic stellate cells. Conclusions: Enhancement of the TNF-α/TNFR mediated signalling pathway via activation of Kupffer cells in an autocrine or paracrine manner may be critically involved in the pathogenesis of liver fibrosis in this NASH animal model. |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| Relation: | http://gut.bmj.com/cgi/content/short/55/3/415; http://dx.doi.org/10.1136/gut.2005.071118 |
| DOI: | 10.1136/gut.2005.071118 |
| الاتاحة: | http://gut.bmj.com/cgi/content/short/55/3/415 https://doi.org/10.1136/gut.2005.071118 |
| Rights: | Copyright (C) 2006, BMJ Publishing Group |
| رقم الانضمام: | edsbas.2C423F0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1136/gut.2005.071118 |
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