Studies on the molecular mechanisms of matrix metalloproteinases regulation in chondrocytes by chemokines

碩士 === 臺北醫學大學 === 醫學技術學系 === 93 === It has been demonstrated that chemokines play an important role in cartilage degradation, however, the underlying molecular mechanisms are not well studied. In this study, we investigated the effects of CC chemokines-eotaxin-1 on the MMP expression in both of huma...

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Main Authors: Chia-Pei Lin, 林佳蓓
Other Authors: Chien-Ho Chen, Ph. D.
Format: Others
Language:en_US
Published: 2005
Online Access:http://ndltd.ncl.edu.tw/handle/94099864010110597664
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spelling ndltd-TW-093TMC001140262015-12-25T04:10:27Z http://ndltd.ncl.edu.tw/handle/94099864010110597664 Studies on the molecular mechanisms of matrix metalloproteinases regulation in chondrocytes by chemokines 趨化激素調控人類軟骨細胞表現間質分解酵素之分子機制探討 Chia-Pei Lin 林佳蓓 碩士 臺北醫學大學 醫學技術學系 93 It has been demonstrated that chemokines play an important role in cartilage degradation, however, the underlying molecular mechanisms are not well studied. In this study, we investigated the effects of CC chemokines-eotaxin-1 on the MMP expression in both of human chondrocyte cell lines SW1353 and primary culture chondrocytes. First, we found that eotaxin-1 significantly induced MMP-3 mRNA expression in a dose-dependent manner. Second, ERK inhibitor and p38 kinase inhibitor were able to repress MMP-3 mRNA expression induced by eotaxin-1. On the other hand, Rp-adenosine-3’,5’-cyclic monophosphorothioate (Rp-cAMPs), a competitive cAMP antagonist for cAMP-receptor proteins, and PKA inhibitor-H89 markedly enhanced the MMP-3 mRNA expression induced by eotaxin-1. There results suggest that MMP-3 expression mainly mediated by eotaxin-1 receptor, which is a Gαi-coupled receptor. Eotaxin-1 also activated the transcription factor AP-1 and NF-κB by EMSA experiment. Interesting finding that no MMP-3 protein was detected in the cell lysate of eotaxin-1 treatment chondrocytes. However, most of MMP-3 protein was secreted into the culture medium in both of chondrocyte cell lines SW1353 and primary culture chondrocytes. We discovered that PLC-PKC cascade and p38 and JNK MAP kinase pathway regulated MMP-3 protein secretion induced by eotaxin-1. There results suggest that MMP-3 secretion mainly mediated by eotaxin-1 receptor, which activate Gβγ subunit. These results suggest that eotaxin-1 not only induced MMP-3 gene expression but also promoted MMP-3 protein secretion, and eotaxin-1 may be a key molecule in the cartilage degradation of arthritis. Chien-Ho Chen, Ph. D. Yu-Chih Liang, Ph. D. 陳建和 梁有志 2005 學位論文 ; thesis 78 en_US
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description 碩士 === 臺北醫學大學 === 醫學技術學系 === 93 === It has been demonstrated that chemokines play an important role in cartilage degradation, however, the underlying molecular mechanisms are not well studied. In this study, we investigated the effects of CC chemokines-eotaxin-1 on the MMP expression in both of human chondrocyte cell lines SW1353 and primary culture chondrocytes. First, we found that eotaxin-1 significantly induced MMP-3 mRNA expression in a dose-dependent manner. Second, ERK inhibitor and p38 kinase inhibitor were able to repress MMP-3 mRNA expression induced by eotaxin-1. On the other hand, Rp-adenosine-3’,5’-cyclic monophosphorothioate (Rp-cAMPs), a competitive cAMP antagonist for cAMP-receptor proteins, and PKA inhibitor-H89 markedly enhanced the MMP-3 mRNA expression induced by eotaxin-1. There results suggest that MMP-3 expression mainly mediated by eotaxin-1 receptor, which is a Gαi-coupled receptor. Eotaxin-1 also activated the transcription factor AP-1 and NF-κB by EMSA experiment. Interesting finding that no MMP-3 protein was detected in the cell lysate of eotaxin-1 treatment chondrocytes. However, most of MMP-3 protein was secreted into the culture medium in both of chondrocyte cell lines SW1353 and primary culture chondrocytes. We discovered that PLC-PKC cascade and p38 and JNK MAP kinase pathway regulated MMP-3 protein secretion induced by eotaxin-1. There results suggest that MMP-3 secretion mainly mediated by eotaxin-1 receptor, which activate Gβγ subunit. These results suggest that eotaxin-1 not only induced MMP-3 gene expression but also promoted MMP-3 protein secretion, and eotaxin-1 may be a key molecule in the cartilage degradation of arthritis.
author2 Chien-Ho Chen, Ph. D.
author_facet Chien-Ho Chen, Ph. D.
Chia-Pei Lin
林佳蓓
author Chia-Pei Lin
林佳蓓
spellingShingle Chia-Pei Lin
林佳蓓
Studies on the molecular mechanisms of matrix metalloproteinases regulation in chondrocytes by chemokines
author_sort Chia-Pei Lin
title Studies on the molecular mechanisms of matrix metalloproteinases regulation in chondrocytes by chemokines
title_short Studies on the molecular mechanisms of matrix metalloproteinases regulation in chondrocytes by chemokines
title_full Studies on the molecular mechanisms of matrix metalloproteinases regulation in chondrocytes by chemokines
title_fullStr Studies on the molecular mechanisms of matrix metalloproteinases regulation in chondrocytes by chemokines
title_full_unstemmed Studies on the molecular mechanisms of matrix metalloproteinases regulation in chondrocytes by chemokines
title_sort studies on the molecular mechanisms of matrix metalloproteinases regulation in chondrocytes by chemokines
publishDate 2005
url http://ndltd.ncl.edu.tw/handle/94099864010110597664
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