The Role of NFkB in (1–>3)-B-Glucan (Zymosan a) Induced TNF-Alpha Production
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2000/01/07
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Description:The signal transduction pathway in the inflammatory response caused by a fungal cell wall component (1-->3)-B-glucan is not well understood. The present study used zymosan A-induced tumor necrosis factor (TNF)-alpha production as a model to explore the signal transduction pathway for B-glucan stimulation in RAW264.7 cells. Zymosan A increased TNF-alpha production in RAW264.7 cells in a time and concentration dependent pattern with the optimal time and concentration occurring at 23 hr and 100 ug/mL zymosan A, respectively. A gel shift assay was used to examine the DNA-binding activity of NFkB in the zymosan A- treated cells. This NFkB activity was enhanced by this stimulant. NFkB activation was associated with TNF-alpha production, since the cells pre-treated with a known NFkB inhibitor (caffeic acid phenethyl ester) decreased both NFkB activation and TNF-alpha production. The dependence of TNF-alpha transcriptional initiation on kB sites was investigated using a luciferase reporter assay. Both wild type and kB-mutated type TNF-alpha promoters were utilized to study the dependence of TNF-alpha promoter on kB sites. The results demonstrated that the activation of TNF-alpha promoter was dependent on the activation of NFkB. A NFkB specific reporter was used in conjunction with TNF-alpha wild type reporter to evaluate the temporal relationship between the NFkB activation and induction of TNF-alpha reporter activity. The results showed that the peak of NFkB activation occurred at 5 hrs which proceeded the peak of TNF-alpha promoter activation (30 hrs). The above results suggest that activation of NFkB is one of the pathways involved in zymosan A-induced TNF-alpha production. [Description provided by NIOSH]
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Pages in Document:15
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NIOSHTIC Number:nn:20021101
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Citation:Proceedings of the 24th Cotton and Other Organic Dusts Research Conference, January 7-8, 2000, San Antonio, TX, Wakelyn-PJ, Jacobs-RR, Rylander-R, eds., Memphis, TN: The National Cotton Council, 2000 Jan; :15
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Federal Fiscal Year:2000
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Peer Reviewed:False
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Source Full Name:Proceedings of the 24th Cotton and Other Organic Dusts Research Conference
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Main Document Checksum:urn:sha-512:0984d6b03680b322193ad8e0eaba894b5b37099d1a18c36192b1d817cbdac8bb0099c8f8c650a5272b99036c8fe5cf9c856195c0e9ac6f72f79b2e59a49ae42d
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