Expression of immunomodulatory genes in human monocytes induced by voriconazole in the presence of Aspergillus fumigatus (Journal article)

Simitsopoulou, M./ Roilides, E./ Likartsis, C./ Ioannidis, J./ Orfanou, A./ Paliogianni, F./ Walsh, T. J.

We assessed the effect of voriconazole (VRC) on the expression and release of selected cytokines and chemokines in the THP-1 human monocytic cell line in response to Aspergillus fumigatus hyphal fragments (HF) by cDNA microarray analysis, reverse transcriptase (RT) PCR, and enzyme-linked immunosorbent assay. Stimulation of THP-1 cells by HF alone caused a significant up-regulation of CCL4 (MIP1B) and CCL16, while CCL2 (MCP1) was down-regulated. By comparison, in the presence of VRC, a large number of genes such as CCL3 (MIP1A), CCL4 (MIP1B), CCL5 (RANTES), CCL7 (MCP3), CCL11 (EOTAXIN), CCL15 (MIP1Delta), CXCL6, and CXCL13 were strongly up-regulated in THP-1 cells challenged by HF, whereas CCL20 (MIP3A) and CCL21 (MIP2) were down-regulated. Among five genes differentially expressed in THP-1 cells, IL12A, IL12B, and IL-16 were down-regulated whereas IL-11 and TGFB1 were significantly up-regulated in the presence of VRC. The inflammation-related genes IFNgamma, IL1R1, and TNFA were also up-regulated in THP-1 cells exposed to HF only in the presence of VRC. RT-PCR of four selected genes validated the results of microarrays. The release of interleukin 1beta (IL-1beta) and IL-12 was significantly increased from monocytes stimulated either by HF alone (P < 0.05) or in the presence of VRC (P < 0.01 and P < 0.05, respectively). In contrast, tumor necrosis factor alpha release from monocytes was enhanced only in the presence of VRC (P < 0.01). The chemokines monocyte chemoattractant protein 1 and macrophage inflammatory protein 1beta were decreased under both conditions (P < 0.01). These results demonstrate that in the presence of VRC, HF induces a more pronounced profile of gene expression in THP-1 cells than HF alone, potentially leading to more-efficient host resistance to A. fumigatus.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: Antifungal Agents/*pharmacology,Aspergillus fumigatus/*immunology,Cells, Cultured,Chemokine CCL2/biosynthesis,Chemokine CCL3,Chemokine CCL4,DNA, Complementary/biosynthesis/genetics,Gene Expression Regulation/*drug effects,Humans,Hyphae/immunology,Immunity, Innate/*drug effects/*genetics,Interleukin-10/biosynthesis,Interleukin-12/biosynthesis,Interleukin-1beta/biosynthesis,Macrophage Inflammatory Proteins/biosynthesis,Monocytes/drug effects/*immunology,Oligonucleotide Array Sequence Analysis,Pyrimidines/*pharmacology,RNA/biosynthesis/genetics,Reverse Transcriptase Polymerase Chain Reaction,Triazoles/*pharmacology,Tumor Necrosis Factor-alpha/biosynthesis
ISSN: 0066-4804
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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