Secretion of interleukin-8 by human-derived cell lines infected withMycobacterium bovis

[摘要] Background: The variable efficacy of bacillus Calmette-Guérin (Mycobacterium bovisBCG) 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 withM.bovisBCG.Methods: The concentrations of IL-8 in culture supernatants of U937 cells or HEp-2 cells infected withM. bovisBCG 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 Ca2+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 Ca2+in order to investigate the mechanisms through whichM.bovisBCG induces IL-8 secretion in our system.Results: The enzyme-linked immunosorbent assay showed that IL-8 protein secretion was elevated inM.bovis-infected cell lines. This effect was statistically significant(p<0.01). When calcium influx was suppressed inM.bovis-infected cell lines, IL-8 secretion was inhibited. Notably, specific inhibitors of NF-κB (sulfasalazine and curcumin) inhibitedM.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 inM.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 withM.bovis.

[学科分类] 生理学与病理学