Regulation of expression of stromyelysin-1 by proinflammatory cytokines in mouse brain astrocytes.
Stromelysin-1 belongs to matrix metalloproteinases responsible for proteolytic degradation of extracellular matrix in many tissues during various diseases, especially those involving inflammation. We studied the induced expression of stromelysin-1 in primary cultures of mouse brain astrocytes stimulated with various cytokines and cellular growth factors. Interleukin-1-beta (IL-1beta), tumor necrosis factor alpha (TNFalpha) and a mixture of IL-1, TNF and epidermal growth factor (EGF) significantly increased the level of stromelysin-1 mRNA in mouse astrocytes while interferon-gamma (IFN-gamma) inhibited this response or was without effect. This accumulation of specific mRNA was preceded by activation of two examined transcription factors: NFkappaB and AP-1. However, experiments with known inhibitors of activation of these transcription factors: pyrrolidine dithiocarbamate (PDTC), parthenolide and curcumin, indicate that NFkappaB and AP-1 cannot be solely responsible for the cytokine induced expression of stromelysin-1 gene in mouse astrocytes.
Witek-Zawada
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Department of Cell Biochemistry, Faculty of Biotechnology, Jagiellonian University, Krakow, Poland. koj@mol.uj.edu.pl
Koj
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D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000166:cytology; D001923:Brain Chemistry / Q000187:drug effects / Q000276:immunology; D018929:Cell Culture Techniques; D003474:Curcumin / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D012717:Sesquiterpenes / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology
D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D016328:NF-kappa B; D011759:Pyrrolidines; D012333:RNA, Messenger; D012717:Sesquiterpenes; D013859:Thiocarbamates; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid; C002669:parthenolide; D004815:Epidermal Growth Factor; D007371:Interferon-gamma; D019278:Matrix Metalloproteinase 3; D003474:Curcumin