Mechanism of Three Inhibitors of TACE in Blocking the Converting of pro-TNFα into sTNFα  

作　　者：王震 王茵 朱孔黎 郭莲军 杨渝珍 

机构地区：[1]Department of Pharmacology,Tongji Medical College,Huazhong University of Science and Technology, Wuhan 430030 [2]Life Sciences College,Wuhan University,Wuhan 430072 [3]Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences,Tongji Medical College, Huazhong University of Science and Technology,Wuhan 430030 [4]Department of Pharmacology,Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 [5]Department of Biochemistry & Molecular Biology,School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 The effects of inhibitors of TNFαconverting enzyme (TACE) on TNFαsecretion werestudied to develop an approach to interfere inflammation processes. The HL-60 cell lines were stimu-lated in vitro with LPS intravenously for different time to establish the cellular model of inflammationand simultaneously induce in vivo inflammation animal model by LPS The cytotoxic effects of solubleTNFαwere checked using MTT colorimetric method to determine the rate of cell proliferation. Thelevel of expression of TACE was detected by using RT-PCR, FCM and immuno-histochemical tech-nique respectively. It was found Chinese medicine Reduqing (RDQ) could inhibit the transcription ofTNFαmRNA induced by LPS stimulation (P<0.01, compared with the control). The anti-oligodeoxyribonucleotide (anti-ODN) of TNFαmRNA could inhibit 78.9% of TNFαsecretion. Themimic peptides of TACE substrates with hydroxamine group showed potency in vivo and in vitro a-gainst converting of pro-TNFα. It was concluded that all the three types of TACE inhibitors can reg-ulate the expression of TACE at different levels and inhibit sTNFαsecretion, indicating TACE is anovel target for inflammation therapy.

出　　处：《Journal of Huazhong University of Science and Technology(Medical Sciences)》2003年第2期116-120,共5页华中科技大学学报（医学英德文版）

基　　金：This project was supported by a grant from National Natural Sciences Foundation of China(No.30070722).

摘　　要：The effects of inhibitors of TNFα converting enzyme (TACE) on TNFα secretion were studied to develop an approach to interfere inflammation processes. The HL-60 cell lines were stimulated in vitro with LPS intravenously for different time to establish the cellular model of inflammation and simultaneously induce in vivo inflammation animal model by LPS The cytotoxic effects of soluble TNFa were checked using MTT colorimetric method to determine the rate of cell proliferation. The level of expression of TACE was detected by using RT-PCR, FCM and immuno-histochemical technique respectively. It was found Chinese medicine Reduqing (RDQ) could inhibit the transcription of TNFa mRNA induced by LPS stimulation (P<0. 01, compared with the control). The anti-oligodeoxyribonucleotide (anti-ODN) of TNFα mRNA could inhibit 78. 9 % of TNFα secretion. The mimic peptides of TACE substrates with hydroxamine group showed potency in vivo and in vitro a-gainst converting of pro-TNFα. It was concluded that all the three types of TACE inhibitors can regulate the expression of TACE at different levels and inhibit sTNFα secretion, indicating TACE is a novel target for inflammation therapy.The effects of inhibitors of TNFα converting enzyme (TACE) on TNFα secretion were studied to develop an approach to interfere inflammation processes. The HL-60 cell lines were stimulated in vitro with LPS intravenously for different time to establish the cellular model of inflammation and simultaneously induce in vivo inflammation animal model by LPS The cytotoxic effects of soluble TNFa were checked using MTT colorimetric method to determine the rate of cell proliferation. The level of expression of TACE was detected by using RT-PCR, FCM and immuno-histochemical technique respectively. It was found Chinese medicine Reduqing (RDQ) could inhibit the transcription of TNFa mRNA induced by LPS stimulation (P<0. 01, compared with the control). The anti-oligodeoxyribonucleotide (anti-ODN) of TNFα mRNA could inhibit 78. 9 % of TNFα secretion. The mimic peptides of TACE substrates with hydroxamine group showed potency in vivo and in vitro a-gainst converting of pro-TNFα. It was concluded that all the three types of TACE inhibitors can regulate the expression of TACE at different levels and inhibit sTNFα secretion, indicating TACE is a novel target for inflammation therapy.

关 键 词：TNFα converting enzyme tumor necrosis factor-α REDUQING anti-oligodeoxyri-bonucleotide peptide inhibitor 

分 类 号：R346[医药卫生—基础医学]