| Chou WY |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=1.123 ------>paper_class3=2 ------>paper_class2=1 ------>vol=27 ------>confirm_bywho=None ------>insert_bywho=kshung ------>Jurnal_Rank=41.6 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=476 ------>medlineContent= ------>unit=000 ------>insert_date=20070501 ------>iam=5 ------>update_date=None ------>author=??? ------>change_event=1 ------>ISSN= ------>authors_c= ------>score=500 ------>journal_name=Acta Pharmacol Sin ------>paper_name=Electroporative interleukin-10 gene transfer ameliorates carbon tetrachloride-induced murine liver fibrosis by MMP and TIMP modulation ------>confirm_date=None ------>tch_id=095047 ------>pmid=16539848 ------>page1=469 ------>fullAbstract=AIM: Liver fibrosis represents a process of healing and scarring in response to chronic liver injury. Effective therapies for liver fibrosis are lacking. Interleukin-10 (IL-10) is a cytokine that downregulates pro-inflammatory responses and has a modulatory effect on hepatic fibrogenesis. The aim of this study was to investigate whether electroporative IL-10 gene therapy has a hepatic fibrolytic effect on mice. METHODS: Hepatic fibrosis was induced by administering carbon tetrachloride (CCl4) for 10 weeks in mice. The human IL-10 expression plasmid was delivered via electroporation after hepatic fibrosis was established. Histopathology, reverse transcription polymerase chain reaction (RT-PCR), immunoblotting, and gelatin zymography were used to investigate the possible mechanisms of action of IL-10. RESULTS: Human IL-10 gene therapy reversed CCl4-induced liver fibrosis in mice. RT-PCR revealed that IL-10 gene therapy attenuated liver TGF-beta1, collagen alpha1, fibronectin, and cell adhesion molecule mRNA upregulation. Following gene transfer, both the activation of alpha-smooth muscle actin and cyclooxygenase-2 were significantly attenuated. Furthermore, IL-10 significantly inhibited matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of matrix metalloproteinase (TIMP) activation after CCl4 intoxication. CONCLUSIONS: We demonstrated that IL-10 gene therapy attenuated CCl4-induced liver fibrosis in mice. IL-10 prevented upregulated fibrogenic and pro-inflammatory gene responses. Its collagenolytic effect may be attributed to MMP and TIMP modulation. IL-10 gene therapy may be an effective therapeutic modality against liver fibrosis with potential clinical use. ------>tmu_sno=None ------>sno=15376 ------>authors2=Lu CN ------>authors3=Lee TH ------>authors4=Wu CL ------>authors5=Hung KS ------>authors6=Concejero AM, Jawan B, Wang CH ------>authors6_c= ------>authors=Chou WY ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Electroporative interleukin-10 gene transfer ameliorates carbon tetrachloride-induced murine liver fibrosis by MMP and TIMP modulation. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=4 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2006 ------>submit_flag=None ------>publish_month=4 |