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Mediators of Inflammation - Volume 13 2004, Issue 1, Pages 45-49

Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, IPN, Carpio y Plan de Ayala, México D.F. 11340, Mexico

Received 28 November 2003; Accepted 10 December 2003

Copyright © 2004 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background: The variable efficacy of bacillus Calmette-Guérin Mycobacterium bovis BCG in protecting humans against tuberculosis has prompted a search for the mechanisms through which BCG induces chemokines. In this study, our experiments were designed to determine the role of the transcription factor nuclear factor-κB NF-κB and intracellular calcium in the production of interleukin IL-8, a main chemotactic factor, by human-derived monocytic cell line U937 and by a human epithelial HEp-2 cell line infected with M. bovis BCG.

Methods: The concentrations of IL-8 in culture supernatants of U937 cells or HEp-2 cells infected with M. bovis BCG were determined by enzyme-linked immunosorbent assay. We used sulfasalazine and curcumin, which are well-described inhibitors of NF-κB activity, and we used ethylenediamine tetraacetic acid to deplete extracellular Ca

or used the cell-permeable agent 1,2-bis 2-aminophenoxy ethane-N,N,N-,N-tetraacetic acid tetra acetoxymethyl ester to chelate releasable intracellular stores of Ca

in order to investigate the mechanisms through which M. bovis BCG induces IL-8 secretion in our system.

Results: The enzyme-linked immunosorbent assay showed that IL-8 protein secretion was elevated in M. bovis-infected cell lines. This effect was statistically significant p<0.01. When calcium influx was suppressed in M. bovis-infected cell lines, IL-8 secretion was inhibited. Notably, specific inhibitors of NF-κB sulfasalazine and curcumin inhibited M. bovis-induced IL-8 secretion from U937 cells or HEp-2 cells.

Conclusions: Collectively, these results indicate that activation of NF-κB is an important signal transduction pathway in M. bovis-induced IL-8 secretion in monocytic or epithelial cells. Furthermore, the results showed that calcium influx had a direct effect on IL-8 secretion in U937 cells or HEp-2 cells infected with M. bovis.

Autor: Patricia Méndez-Samperio, Janet Palma-Barrios, Abraham Vázquez-Hernández, and Elizabeth García-Martínez



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