Microarray analysis of amphotericin B-treated THP-1 monocytic cells identifies unique gene expression profiles among lipid and non-lipid drug formulations

J Chemother. 2008 Jun;20(3):327-35. doi: 10.1179/joc.2008.20.3.327.

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-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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amphotericin B / adverse effects
  • Amphotericin B / chemistry
  • Amphotericin B / pharmacology*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Drug Compounding
  • Gene Expression / drug effects*
  • Gene Expression Profiling*
  • Humans
  • Lipids / chemistry
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Oligonucleotide Array Sequence Analysis
  • Up-Regulation

Substances

  • Anti-Bacterial Agents
  • Lipids
  • Amphotericin B