1. Differential transcriptional profiles induced by amphotericin B formulations on human monocytes during response to hyphae ofAspergillus fumigatus
- Author
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Fotini Paliogianni, Emmanuel Roilides, Elpiniki Georgiadou, Maria Simitsopoulou, and Thomas J. Walsh
- Subjects
Chemokine ,Antifungal Agents ,Hyphae ,Gene Expression ,Biology ,Aspergillosis ,Monocytes ,Cell Line ,Microbiology ,Aspergillus fumigatus ,Aldesleukin ,Amphotericin B ,Amphotericin B deoxycholate ,medicine ,Humans ,Immunologic Factors ,Reverse Transcriptase Polymerase Chain Reaction ,Effector ,Gene Expression Profiling ,Monocyte ,General Medicine ,Microarray Analysis ,biology.organism_classification ,medicine.disease ,Molecular biology ,Drug Combinations ,Infectious Diseases ,medicine.anatomical_structure ,biology.protein ,Cytokines ,Deoxycholic Acid ,medicine.drug - 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.
- Published
- 2011