Microarray Analysis of Amphotericin B-Treated THP-1 Monocytic Cells Identifies Unique Gene Expression Profiles Among Lipid and Non-Lipid Drug Formulations

Authors: Turtinen, L.W.; Croswell, A.; Obr, A.

Source: Journal of Chemotherapy, Number 3, June 2008 , pp. 327-335(9)

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Abstract:

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-3α), and CXCL2 (MIP-2α). 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

Keywords: Amphotericin B; microarray; THP-1 monocytes; ABLC; antifungal agents; ABCD

Document Type: Research Article

Publication date: 2008-06-01

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