INVESTIGATION OF THE EFFECTS OF ARISTOLOCHIC ACID ON MONOCYTIC MATRIX METALLOPROTEINASE-9 ACTIVATION AND NON-SPECIFIC IMMUNE FUNCTION

碩士 === 臺北醫學大學 === 藥理學研究所 === 93 === Many evidence indicated that rheumatoid arthritis (RA) is a disease including immune and inflammatory systems which are linked to the destruction of cartilage and bone. Monocyte/macrophages, lymphocytes and fibroblasts are found in highly increased numbers in the...

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Main Authors: Yung-Chen Chou, 周泳臣
Other Authors: George Hsiao
Format: Others
Language:zh-TW
Published: 2005
Online Access:http://ndltd.ncl.edu.tw/handle/54456307752248704440
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spelling ndltd-TW-093TMC005500012015-10-13T11:39:46Z http://ndltd.ncl.edu.tw/handle/54456307752248704440 INVESTIGATION OF THE EFFECTS OF ARISTOLOCHIC ACID ON MONOCYTIC MATRIX METALLOPROTEINASE-9 ACTIVATION AND NON-SPECIFIC IMMUNE FUNCTION 探討馬兜鈴酸對第九型基質金屬蛋白酵素活化與非特異性免疫功能作用的機轉 Yung-Chen Chou 周泳臣 碩士 臺北醫學大學 藥理學研究所 93 Many evidence indicated that rheumatoid arthritis (RA) is a disease including immune and inflammatory systems which are linked to the destruction of cartilage and bone. Monocyte/macrophages, lymphocytes and fibroblasts are found in highly increased numbers in the synovial membrane in RA. Leukocytes and synovial fibroblast overproduce pro-inflammatory cytokines, mainly tumor necrosis factor-alpha (TNF-), interleukin (IL)-1 and IL-6, which lead to chronic inflammation. These cytokines activate a variety of gene expression, including genes coding for various cytokines and matrix metalloproteinases (MMPs) involved in tissue degradation. On the other way, MMPs also play an important role in tumor invasion. The invasive properties of tumor cells, owing to their ability to degrade all major protein components of the extracellular matrix (ECM) and basement membranes. They also participate in early steps of tumor evolution, including stimulation of cell proliferation and modulation of angiogenesis. We found that aristolochic acids (AsA) extracted from herbal medicines (such as Aristolochia spp) showed obviously inhibitory effect on MMPs activation. In this study, we found that AsA was shown to inhibit the TNF--induced MMP-9 activation and expression in human monocyte THP-1 cells by zymography method and Western Blot (IC50= 6.41 ± 0.45 M). We also found the different ratio (I : II = 55:42 and 29:66) of aristolochic acids I and II with similar effect on inhibition of MMP-9 activation. We also used indomethacin to exclude the inhibitory action of AsA involved in prostaglandin pathway. In the transcription level, AsA suppressed the TNF--induced MMP-9 mRNA expression by using RT-PCR. AsA also inhibit the TNF--induced IB- degradation. In the nuclear aspect, we also found that AsA inhibited TNF--induced NF-B activation (by EMSA method) and translocation. Interestingly, AsA was shown to concentration-dependently inhibit the concanavalin A (Con A) and lipopolysaccharide (LPS) induced proliferation of mouse splenocytes. We also compare the inhibitory effect of AsA with dehydroepiandrosterone (DHEA), and the inhibitory effect is similar. By the way, the cytokines (IL-2 and interferon-) released from the ConA-induced lymphocyte were concentration-dependently affected. However, the inhibitory mechanisms of AsA on lymphocyte need further investigated. It will be interesting to study further the anti-inflammatory activities of this nature compound on RA-related synovial injuries in vivo. George Hsiao 蕭哲志 2005 學位論文 ; thesis 150 zh-TW
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description 碩士 === 臺北醫學大學 === 藥理學研究所 === 93 === Many evidence indicated that rheumatoid arthritis (RA) is a disease including immune and inflammatory systems which are linked to the destruction of cartilage and bone. Monocyte/macrophages, lymphocytes and fibroblasts are found in highly increased numbers in the synovial membrane in RA. Leukocytes and synovial fibroblast overproduce pro-inflammatory cytokines, mainly tumor necrosis factor-alpha (TNF-), interleukin (IL)-1 and IL-6, which lead to chronic inflammation. These cytokines activate a variety of gene expression, including genes coding for various cytokines and matrix metalloproteinases (MMPs) involved in tissue degradation. On the other way, MMPs also play an important role in tumor invasion. The invasive properties of tumor cells, owing to their ability to degrade all major protein components of the extracellular matrix (ECM) and basement membranes. They also participate in early steps of tumor evolution, including stimulation of cell proliferation and modulation of angiogenesis. We found that aristolochic acids (AsA) extracted from herbal medicines (such as Aristolochia spp) showed obviously inhibitory effect on MMPs activation. In this study, we found that AsA was shown to inhibit the TNF--induced MMP-9 activation and expression in human monocyte THP-1 cells by zymography method and Western Blot (IC50= 6.41 ± 0.45 M). We also found the different ratio (I : II = 55:42 and 29:66) of aristolochic acids I and II with similar effect on inhibition of MMP-9 activation. We also used indomethacin to exclude the inhibitory action of AsA involved in prostaglandin pathway. In the transcription level, AsA suppressed the TNF--induced MMP-9 mRNA expression by using RT-PCR. AsA also inhibit the TNF--induced IB- degradation. In the nuclear aspect, we also found that AsA inhibited TNF--induced NF-B activation (by EMSA method) and translocation. Interestingly, AsA was shown to concentration-dependently inhibit the concanavalin A (Con A) and lipopolysaccharide (LPS) induced proliferation of mouse splenocytes. We also compare the inhibitory effect of AsA with dehydroepiandrosterone (DHEA), and the inhibitory effect is similar. By the way, the cytokines (IL-2 and interferon-) released from the ConA-induced lymphocyte were concentration-dependently affected. However, the inhibitory mechanisms of AsA on lymphocyte need further investigated. It will be interesting to study further the anti-inflammatory activities of this nature compound on RA-related synovial injuries in vivo.
author2 George Hsiao
author_facet George Hsiao
Yung-Chen Chou
周泳臣
author Yung-Chen Chou
周泳臣
spellingShingle Yung-Chen Chou
周泳臣
INVESTIGATION OF THE EFFECTS OF ARISTOLOCHIC ACID ON MONOCYTIC MATRIX METALLOPROTEINASE-9 ACTIVATION AND NON-SPECIFIC IMMUNE FUNCTION
author_sort Yung-Chen Chou
title INVESTIGATION OF THE EFFECTS OF ARISTOLOCHIC ACID ON MONOCYTIC MATRIX METALLOPROTEINASE-9 ACTIVATION AND NON-SPECIFIC IMMUNE FUNCTION
title_short INVESTIGATION OF THE EFFECTS OF ARISTOLOCHIC ACID ON MONOCYTIC MATRIX METALLOPROTEINASE-9 ACTIVATION AND NON-SPECIFIC IMMUNE FUNCTION
title_full INVESTIGATION OF THE EFFECTS OF ARISTOLOCHIC ACID ON MONOCYTIC MATRIX METALLOPROTEINASE-9 ACTIVATION AND NON-SPECIFIC IMMUNE FUNCTION
title_fullStr INVESTIGATION OF THE EFFECTS OF ARISTOLOCHIC ACID ON MONOCYTIC MATRIX METALLOPROTEINASE-9 ACTIVATION AND NON-SPECIFIC IMMUNE FUNCTION
title_full_unstemmed INVESTIGATION OF THE EFFECTS OF ARISTOLOCHIC ACID ON MONOCYTIC MATRIX METALLOPROTEINASE-9 ACTIVATION AND NON-SPECIFIC IMMUNE FUNCTION
title_sort investigation of the effects of aristolochic acid on monocytic matrix metalloproteinase-9 activation and non-specific immune function
publishDate 2005
url http://ndltd.ncl.edu.tw/handle/54456307752248704440
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