Microarray analysis of amphotericin B-treated THP-1 monocytic cells identifies unique gene expression profiles among lipid and non-lipid drug formulations.
The effects of deoxycholate amphotericin B (DAmB), amphotericin B lipid complex (ABLC), and amphotericin B colloidal dispersion (ABCD) on mRNA profiles from 218 genes in treated THP-1 monocytes were compared. Sixty-one genes were up-regulated and 8 were down-regulated by one or more of the AmB formulations. Fifty-three genes were up-regulated by DAmB while 24 and 18 genes were up-regulated by ABCD and ABLC, respectively. DAmB and ABCD up-regulated many pro-inflammatory genes, whereas ABLC did not. All three formulations up-regulated multiple categories of genes including the anti-apoptosis gene BIRC3 and the chemokine CXCL9 (MIG). Based on representative genes, DAmB activated more signaling pathways than ABCD or ABLC. Quantitative real time PCR confirmed array up-regulation of representative pro-inflammatory genes IL-8, CCL20 (MIP-3alpha), and CXCL2 (MIP-2alpha). Our study represents the first larger scale comparative gene expression profiling which may provide additional rationales for clinical side effects of each amphotericin B formulation.
Turtinen
L W
LW
Department of Biology, university of Wisconsin-Eau Claire, Eau Claire, WI 54702, USA.turtinen@uwec.edu
Croswell
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Obr
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D000666:Amphotericin B / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D004339:Drug Compounding; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D008055:Lipids / Q000737:chemistry; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D015854:Up-Regulation
D000900:Anti-Bacterial Agents; D008055:Lipids; D000666:Amphotericin B