{"doi":"10.1128/aac.01095-06","title":"Expression of Immunomodulatory Genes in Human Monocytes Induced by Voriconazole in the Presence of<i>Aspergillus fumigatus</i>","abstract":"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.","journal":"Antimicrobial Agents and Chemotherapy","year":2007,"id":2112,"datarank":0.5709993734655481,"base_score":3.8066624897703196,"endowment":3.8066624897703196,"self_citation_contribution":0.5709993734655481,"citation_network_contribution":0.0,"self_endowment_contribution":0.5709993734655481,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":44,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0413,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2007-03-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":24292,"name":"E. Roilides","orcid":null,"position":1,"is_corresponding":false},{"id":24293,"name":"C. Likartsis","orcid":null,"position":2,"is_corresponding":false},{"id":24294,"name":"A. Orfanou","orcid":null,"position":4,"is_corresponding":false},{"id":24295,"name":"F. Paliogianni","orcid":null,"position":5,"is_corresponding":false},{"id":24296,"name":"T. J. Walsh","orcid":null,"position":6,"is_corresponding":false},{"id":24297,"name":"Maria Simitsopoulou","orcid":null,"position":7,"is_corresponding":false},{"id":24298,"name":"Emmanuel Roilides","orcid":"0000-0002-0202-364X","position":8,"is_corresponding":false},{"id":24299,"name":"Christodoulos Likartsis","orcid":null,"position":9,"is_corresponding":false},{"id":148,"name":"John P. A. Ioannidis","orcid":"0000-0003-3118-6859","position":10,"is_corresponding":false},{"id":24300,"name":"Aspasia Orfanou","orcid":"0000-0001-7590-6235","position":11,"is_corresponding":false},{"id":24301,"name":"Fotini Paliogianni","orcid":"0000-0001-5112-1724","position":12,"is_corresponding":false},{"id":24302,"name":"Thomas J. Walsh","orcid":"0000-0002-4142-8711","position":13,"is_corresponding":false},{"id":24291,"name":"M. Simitsopoulou","orcid":null,"position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}