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標題: Ornithine decarboxylase interferes with macrophage-like differentiation and matrix metalloproteinase-9 expression by tumor necrosis factor alpha via NF-kappa B
作者: Liao, Y.F.
Hung, H.C.
Hsu, P.C.
Kao, M.C.
Hour, T.C.
Tsay, G.J.
Liu, G.Y.
關鍵字: ODC;MMP-9;TNF-alpha;NF-kappa B;differentiation;promyelocytic leukemia-cells;gene-expression;tnf-alpha;autocrine;regulation;phorbol-ester;monocytic differentiation;polyamine;depletion;92-kda gelatinase;induced apoptosis;immune-response
Project: Leukemia Research
期刊/報告no:: Leukemia Research, Volume 32, Issue 7, Page(s) 1124-1140.
Ornithine decarboxylase (ODC), a tumor promoter, provokes cell proliferation, and inhibits cell death; but the mechanism involved in cell differentiation remains unknown. Herein, we examine whether it functions during macrophage-like differentiation. Previous studies reveal that ODC. a rate-limiting enzyme of polyamine biosynthesis, and polyamines are involved in restraining immune response in activated macrophage. By using 12-O-tetradecanoylphorbol-13-acetate (TPA)-differentiated human promyelocytic HL-60 and promonocytic U-937 cells, we discover that polyamines block the expression, secretion and activation of MMP-9. Meanwhile conventional expression of ODC represses tumor necrosis factor-alpha (TNF-alpha) expression and nuclear factor-kappaB (NF-kappa B) activation as well as MMP-9 enzyme activity. Following stimulation by TNF-alpha, the secretion of MMP-9 is restored in ODC-overexpressed cells. In addition, the NF-kappa B inhibitors (pyrrolidinedithiocarbamate, BAY-11-7082 and lactacystin) suppress the TPA-induced MMP-9 enzyme activity. Concurrently, both the irreversible inhibitor of ODC, alpha-difluoromethytomithine, and TNF-a could not recover MMP-9 activation following NF-kappa B inhibitor treatment in parental cells. Furthermore, ODC could directly inhibit and attenuate NF-kappa B DNA binding and transcriptional activation. Therefore, we suggest that ODC inhibits the TNF-alpha-elevated MMP-9 activation via NF-kappa B as TPA-induced macrophage-like differentiation and this interrupting mechanism may provide a new conceivable resolution why leukemia is poorly differentiated besides atypical growth. (c) 2007 Elsevier Ltd. All rights reserved.
ISSN: 0145-2126
DOI: 10.1016/j.leukres.2007.11.019
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