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PROTEOSOME INHIBITOR ENHANCES ANTI-FIBROTIC EFFICACY OF TLR3-STIMULATING AGENT IN HEPATIC FIBROSIS
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Yang, J. I. | - |
dc.contributor.author | Yoon, J. -H. | - |
dc.contributor.author | Myung, S. J. | - |
dc.contributor.author | Kim, D. | - |
dc.contributor.author | Kim, B. H. | - |
dc.contributor.author | Jung, E. U. | - |
dc.contributor.author | Lee, H. -S. | - |
dc.contributor.author | Lee, Y. J. | - |
dc.contributor.author | Lee, J. S. | - |
dc.contributor.author | Kim, Y. J. | - |
dc.contributor.author | Lee, J. -H. | - |
dc.contributor.author | Kim, H. Y. | - |
dc.date.accessioned | 2012-06-28T01:48:58Z | - |
dc.date.available | 2012-06-28T01:48:58Z | - |
dc.date.issued | 2009 | - |
dc.identifier.citation | JOURNAL OF HEPATOLOGY; Vol.50 ; S119-S119 | ko_KR |
dc.identifier.issn | 0168-8278 | - |
dc.identifier.uri | https://hdl.handle.net/10371/77714 | - |
dc.description.abstract | Background and Aims: Activated hepatic Natural Killer (NK) cells can
attenuate hepatic fibrosis by killing activated hepatic stellate cells (HSCs) in a TRAIL-dependent manner. Since proteosome inhibitors can induce TRAIL receptor expression and TLR3 stimulation can activate NK cells, we attempted to examine if simultaneous treatment of proteosome inhibitor may enhance anti-fibrotic efficacy of TLR3 stimulating agent in hepatic fibrosis. Methods: Hepatic fibrosis in vivo model was established in 8 BALB/c mice in each group by injecting thioacetamide intraperitoneally three times per week for 6 weeks. Polyinosinic:polycytidylic acid (poly I:C) was used as an NK cell-activating agent, which is mediated via TLR3 stimulation, and Bortezomib was used as a proteosome inhibitor. Poly I:C and Bortezomib were administered intraperitoneally for 5 weeks. Hepatic fibrosis was assessed by morphometric analysis of histological findings. HSC apoptosis was assessed by double staining for TUNEL and a smooth muscle actin. Results: There were no differences in mortality: 3 died in control mice, mice treated with poly I:C and mice treated with poly I:C + Bortezomib, and 2 died in mice treated with Bortezomib. There were no significant differences in mean body weight among 4 groups. AST and ALT were higher in control mice and mice treated with Bortezomib than in mice treated with poly I:C and mice treated with poly I:C + Bortezomib. The extent of collagen deposition was significantly decreased in mice treated with poly I:C + Bortezomib as compared to control or single compoundtreated mice (Figure 1, *p<0.001). The number of TUNEL-positive HSCs was markedly increased in mice treated with poly I:C + Bortezomib as compared to control or single compound-treated mice. Conclusions: These results demonstrate that proteosome inhibitor enhances anti-fibrotic efficacy of TLR3-stimulating agent in in vivo model of hepatic fibrosis. Therefore, this combination strategy may therapeutically be implicated in hepatic fibrosis. | ko_KR |
dc.language.iso | en | ko_KR |
dc.publisher | ELSEVIER SCIENCE BV | ko_KR |
dc.title | PROTEOSOME INHIBITOR ENHANCES ANTI-FIBROTIC EFFICACY OF TLR3-STIMULATING AGENT IN HEPATIC FIBROSIS | ko_KR |
dc.type | Article | ko_KR |
dc.citation.journaltitle | JOURNAL OF HEPATOLOGY | - |
dc.description.tc | 0 | - |
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