Differential transcriptional profiles induced by amphotericin B formulations on human monocytes during response to hyphae of Aspergillus fumigatus.
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.
Simitsopoulou
Maria
M
Laboratory of Infectious Diseases, 3rd Department of Pediatrics, School of Medicine, Aristotle University, Hippokration Hospital, Thessaloniki, Greece.
Roilides
Emmanuel
E
Georgiadou
Elpiniki
E
Paliogianni
Fotini
F
Walsh
Thomas J
TJ
D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004338:Drug Combinations; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D025301:Hyphae / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology*; D046228:Microarray Analysis; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000935:Antifungal Agents; D016207:Cytokines; D004338:Drug Combinations; D007155:Immunologic Factors; C068538:liposomal amphotericin B; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination