Differential transcriptional profiles induced by amphotericin B formulations on human monocytes during response to hyphae of Aspergillus fumigatus.
Τίτλος | Differential transcriptional profiles induced by amphotericin B formulations on human monocytes during response to hyphae of Aspergillus fumigatus. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Simitsopoulou, M., Roilides E., Georgiadou E., Paliogianni F., & Walsh T. J. |
Journal | Med Mycol |
Volume | 49 |
Issue | 2 |
Pagination | 176-85 |
Date Published | 2011 Feb |
ISSN | 1460-2709 |
Λέξεις κλειδιά | Amphotericin B, Antifungal Agents, Aspergillus fumigatus, Cell Line, Cytokines, Deoxycholic Acid, Drug Combinations, Gene Expression, Gene Expression Profiling, Humans, Hyphae, Immunologic Factors, Microarray Analysis, Monocytes, Reverse Transcriptase Polymerase Chain Reaction |
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. |
DOI | 10.3109/13693786.2010.510539 |
Alternate Journal | Med. Mycol. |
PubMed ID | 20807031 |