Abstract
Amphotericin B formulations possess diverse immunomodulatory properties that may contribute to the activity of phagocytes against invasive aspergillosis. In this work we provide a novel set of data on different gene transcriptional profiles of monocytes exposed to the combination of Aspergillus fumigatus and amphotericin B formulations. We used pathway-specific microarray analysis, RT-PCR analysis and enzyme-linked immunosorbent assays to compare the effects of amphotericin B deoxycholate (DAMB) at 1 μg/ml and amphotericin B lipid complex (ABLC) at 5 μg/ml to assess gene expression of immune molecules of THP-1 cells exposed to A. fumigatus hyphae (AF) for 4 h. A. fumigatus hyphae at effector/target ratio 10/1 induced mostly chemotactic factors for monocyte recruitment. DAMB at 1 μg/ml in the presence or absence of AF induced the most pronounced changes in pro-inflammatory and chemokine gene expression, while ABLC under the same conditions caused less dramatic effect. There was a reciprocal response of increased expression of the genes encoding IL-1β and IL-20 and decreased expression of IL-10, IL-2 and IL-3 in response of monocytes to both the hyphae and antifungal agents. These results demonstrate that amphotericin B formulations exert differential effects on genes encoding pro-inflammatory molecules, immunoregulatory molecules and chemokines by human monocytes during response to A. fumigatus and that these molecules may affect antifungal activity.
Acknowledgements
This research was supported in part by a research grant from Enzon Pharmaceuticals Inc. to the Aristotle University of Thessaloniki and by the intramural research program of the National Cancer Institute.
Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.
This paper was first published online on Early Online on 31 August 2010.