Differential expression of genes encoding immunomodulatory proteins in response to amphotericin B in human mononuclear cells identified by cDNA microarray analysis.
Amphotericin B (AMB) is an antifungal agent that possesses immunomodulatory properties that may contribute to its infusion-related toxicity and activity. It has previously been shown to induce the expression of genes encoding the cytokines interleukin (IL)-1 beta and tumour necrosis factor (TNF)-alpha and the chemokines IL-8 and macrophage inflammatory protein (MIP)-1 beta in the human monocytic cell line THP-1. In an effort to identify additional AMB-responsive genes, the gene expression profiles of both THP-1 cells and human peripheral blood mononuclear cells (hPBMCs) on exposure to AMB were assessed using cDNA microarray analysis. In addition to genes known to be AMB responsive, we found the genes encoding IL-1 alpha and MIP-1 alpha to be AMB responsive in both THP-1 cells and hPBMCs. Increases in MIP-1 alpha and MIP-1 beta were also observed in the supernatants of hPBMCs exposed to AMB. The expression of several genes in response to AMB was unique to either cell type. Furthermore, variability in gene expression in hPBMCs was observed between donors. These genes and respective gene products may have significance in the infusion-related toxicity and activity of AMB.
Rogers
P David
PD
Department of Pharmacy Practice, Division of Infectious Diseases, University of Mississippi School of Pharmacy, Jackson, 39216-4505, USA. drogers@uttmem.edu
Pearson
Margaret M
MM
Cleary
John D
JD
Sullivan
Donna C
DC
Chapman
Stanley W
SW
D000276:Adjuvants, Immunologic / Q000235:genetics* / Q000494:pharmacology; D000666:Amphotericin B / Q000494:pharmacology*; D002460:Cell Line; D054407:Chemokine CCL4; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000706:statistics & numerical data; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics* / Q000502:physiology
D000276:Adjuvants, Immunologic; D054407:Chemokine CCL4; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D011506:Proteins; D000666:Amphotericin B