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The Role of NF-kB in 1-3-b-Glucan (Zymosan) Induced TNF-a Production

S. Young, J. Ye, D. G. Frazer, X. Shi and V. Castranova


 
ABSTRACT

The signal transduction pathway of inflammatory response to 1 3-b-glucans, a fungal cell wall component, is not well understood. Tumor necrosis factor (TNF)- is an important cytokine in inflammation. The present study used zymosan A (a source of 1 3-b-glucans)-induced TNF- production as a model to explore the signal transduction pathway of 1 3-b-glucans. The results show that zymosan A induced TNF- production by mouse macrophage RAW264.7 cells in a time- and concentration-dependent pattern. The optimal concentration of zymosan A was 100 g/ml for TNF- stimulation. The TNF- level reached a plateau around 12.5 hrs in the cell culture medium. The mechanism of zymosan A-induced TNF- production was investigated at the gene transcription level. The gel shift assay was used to examine the DNA-binding activity of NF- B in the zymosan A- treated cells. The results showed that NF- B activity was increased by zymosan A, and this activation was associated with TNF- production. A luciferase reporter controlled by the TNF- promoter was utilized to examine promoter activity of the TNF- gene in transiently transfected RAW264.7 cells. The results demonstrated that zymosan A could activate the gene promoter and the induced-promoter activity peaked at 24 hours after zymosan A stimulation. The promoter response depended on the NF- B binding site as verified by using a NF- B inhibitor (caffeic acid phenethyl ester) and by mutation of the NF- B binding site in the promoter. Combined together, these results suggest that activation of NF- B is a very important pathway by which zymosan A induces TNF- expression.



Reprinted from Proceedings of the 2000 Beltwide Cotton Conferences pp. 241 - 247
©National Cotton Council, Memphis TN

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Document last modified Saturday, Jun 17 2000