Mechanism of three inhibitors of TACE in blocking the converting of pro-TNFα into sTNFα

Abstract

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 stimulatedin vitro with LPS intravenously for different time to establish the cellular model of inflammation and simultaneously inducein vivo inflammation animal model by LPS The cytotoxic effects of soluble TNFα 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 TNFα mRNA induced by LPS stimulation (P<0.01, compared with the control). The antioligodeoxyribonucleotide (anti-ODN) of TNFα mRNA could inhibit 78.96% of TNFα secretion. The mimic peptides of TACE substrates with hydroxamine group showed potencyin vivo andin vitro against 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.

Keywords

TNFα converting enzyme / tumor necrosis factor-α / Reduqing / anti-oligodeoxyribonucleotide / peptide inhibitor

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