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Dexamethasone increases susceptibility of Aspergillus fumigatus to hydrogen peroxide via down-regulation of Afyapl gene expression in vitro

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Chinese Medical Journal 2011年第22期124卷 3773-3777页

作者： XU Hui LI Li-juan WAN Zhe LI Ruo-yu LIU Wei Department of Dermatology Peking University First Hospital and Research Center for Medical Mycology Peking University Beijing 100034 China

Background Glucocorticoid is speculated to be able to have Aspergillus fumigatus （A. tum/gatus） I^e~ng more susceptible to reactive oxygen species （ROS） by inhibiting Afyapl, the transcription factor activating protein-1 （AP-1） homologue in A. fumigatus, which may provide a clue to expand the clinical use of glucocorticoid in patients with fungal infections. In this study, we used dexamethasone to determine the direct effect on oxidative killing susceptibility of A. fumigatus in vitro, as well as the expression level of Afyapl gene and its target genes （catalase and superoxide dismutase （SOD） genes）. Methods A. fumigatus spores were treated with different concentrations （0, 0.02, 0.2 mg/ml） of glucocorticoids and assigned to four groups （A： 0.5 hour, B： 2 hours, C： 7 hours, D： 16 hours） according to the time of treatment. The H202 oxidative killing assay was done, using the standard method-spot test, in each group of A. fumigatus. We measured the oxidative killing susceptibility as well as the expression level of the gene Afyapl, CATA, SOD1 and SOD2 in A. fumigatus at each group. The antifungal susceptibility to itraconazole and amphotericin B in each group of A. fumigatus was also measured with M38-A2 method. Results The oxidative killing susceptibility of A. fumigatus was increased, consistent with the reduction of Afyapl, CATA, SOD1 and SOD2 gene expression level after being treated with dexamethasone for 0.5 hours. However, these observations were disappeared along with being treated for longer time. The antifungal susceptibility to itraconazole and amphotericin B in the A. fumigatus strains treated with dexamethasone indicated no change, compared with those without dexamethasone treatment. Conclusion Dexamethasone can have A. fumigatus being more susceptible to ROS when treated for shorter period （0.5 to 2 hours） via the reduction of Afyapl gene expression as well as the down-stream enzyme-coding gene expression.

关键词： Aspergillus fumigatus Afyapl dexamethasone oxidative killing

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