| Differential role of p38 in IL-1alpha induction of MMP-9 and MMP-13 in an established liver myofibroblast cell line. | |
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MedLine Citation:
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PMID: 14631115 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Interleukin-1 (IL-1) has been implicated in the regulation of the expression of various matrix metalloproteinases (MMPs) in many mesenchymal cell types, but its role in liver myofibroblasts (MFs) has not been elucidated. A myofibroblast-like cell line, MG2, was derived from an isolate of rat hepatic stellate cells (HSCs). These cells expressed desmin, vimentin, smooth muscle alpha-actin, and fibulin-2. Using a recombinant IL-1alpha at 5 ng/ml, it was shown that IL-1alpha would upregulate, while IL-1Ra, an IL-1 receptor antagonist, would down-regulate the expression of IL-1alpha mRNA in MG2 cells, indicating the presence of an autostimulatory loop of IL-1alpha in these cells. Besides, a paracrine source of IL-1 may be produced from Kupffer cells, as we showed primarily cultured Kupffer cells responded much more remarkably than MG2 cells to lipopolysaccharide stimuli to produce both IL-1alpha and IL-1beta. Recombinant IL-1alpha upregulated the expression of both MMP-9 and -13, and the induction of MMP-13 but not MMP-9 could be inhibited by SB203580, an inhibitor of p38. Similarly, in primarily cultured human liver MFs, upregulation of MMP-1 by IL-1alpha was also shown to be inhibited by SB203580. All of these data suggested that, during liver inflammation, IL-1 produced by an autocrine model from MFs or by a paracrine model from Kupffer cells might play a crucial role in the remodeling of liver fibrosis through an either p38-dependent or p38-independent pathway to regulate the expression of various MMPs by liver MFs. |
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Authors:
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Hsuan-Shu Lee; Luo-Hwa Miau; Chien-Hung Chen; Ling-Ling Chiou; Guan-Tarn Huang; Pei-Ming Yang; Jin-Chuan Sheu |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of biomedical science Volume: 10 ISSN: 1021-7770 ISO Abbreviation: J. Biomed. Sci. Publication Date: 2003 Nov-Dec |
Date Detail:
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Created Date: 2003-11-21 Completed Date: 2004-02-24 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9421567 Medline TA: J Biomed Sci Country: Switzerland |
Other Details:
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Languages: eng Pagination: 757-65 Citation Subset: IM |
Copyright Information:
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Copyright 2003 National Science Council, ROC and S. Karger AG, Basel |
Affiliation:
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Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chang-Shan South Road, Taipei 100, Taiwan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Northern Cell Count Cell Line, Tumor Collagenases / metabolism* Down-Regulation / drug effects* Enzyme-Linked Immunosorbent Assay Histological Techniques Humans Imidazoles / metabolism Interleukin-1 / pharmacology* Kupffer Cells / drug effects Lipopolysaccharides / metabolism Liver Cirrhosis / physiopathology Matrix Metalloproteinase 13 Matrix Metalloproteinase 9 / metabolism* Mitogen-Activated Protein Kinases / antagonists & inhibitors, metabolism* Pyridines / metabolism Rats Rats, Wistar Reverse Transcriptase Polymerase Chain Reaction Up-Regulation / drug effects* p38 Mitogen-Activated Protein Kinases |
| Chemical | |
Reg. No./Substance:
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0/Imidazoles; 0/Interleukin-1; 0/Lipopolysaccharides; 0/Pyridines; 0/SB 203580; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.4.24.-/Collagenases; EC 3.4.24.-/MMP13 protein, human; EC 3.4.24.-/Matrix Metalloproteinase 13; EC 3.4.24.-/Mmp13 protein, rat; EC 3.4.24.35/Matrix Metalloproteinase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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