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

Turtinen, Lloyd W.; Croswell, A.; Obr, Alison E.

doi:10.1179/joc.2008.20.3.327

Cited by 6 publications

(4 citation statements)

References 17 publications

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“…Likewise, the minimal changes we observed in PRR transcription were consistent with Simitsopoulou et al 19 . The transcriptional modifications induced by amphotericin B deoxycholate alone agree with previous works 19 , 20 . In the presence of A. fumigatus , the strong transcriptions of CCL2, CCL20, IL10 and IL1β that we observed were not previously noted 19 .…”

Section: Discussionsupporting

confidence: 91%

“…Yet, similar experiments were conducted by Turtinen et al . 20 , using amphotericin B lipid complex: the overall minimal effect of these formulations on chemokines transcription was also found here with liposomal amphotericin B (except CXCL10, significantly upregulated with Amphotericin B Lipid Complex). The observed moderate upregulation of IFN gamma transcription observed by Turtinen et al .…”

Section: Discussionsupporting

confidence: 76%

“…The observed moderate upregulation of IFN gamma transcription observed by Turtinen et al . 20 was not observed here. It is plausible that discrepancies in experimental protocols (duration of incubation, concentrations of antifungals, multiplicity of infection, type of Aspergillus strain, morphologic form of Aspergillus used) played a role in this heterogeneity.…”

Section: Discussioncontrasting

confidence: 44%

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Antifungals influence the immune-related transcriptomic landscape of human monocytes after Aspergillus fumigatus infection

Henry

Klement

Gohir

et al. 2022

Sci Rep

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The heterogeneity of clinical responses to antifungals in aspergillosis is partially understood. We hypothesized that besides direct antifungal effects, these discrepancies may be related to different immunomodulatory profiles. Human THP-1 monocytes were coincubated in vitro with Aspergillus fumigatus and variable concentrations of voriconazole (0.5, 1 and 2 mg/l), caspofungin (1 and 2 mg/l), amphotericin B deoxycholate (0.25, 0.5 and 1 mg/l) and liposomal amphotericin B (1, 2 and 3 mg/l). After 6 h of coincubation, total cellular RNA was extracted, converted into cDNA, and transcription of 84 genes involved in antifungal immunity was measured through RT-qPCR. The presence of A. fumigatus was the main driver of the global immune-related transcriptomic response. After Aspergillus infection, thirty genes were upregulated, while 19 genes were downregulated. Discrepancies across antifungals were also evident; voriconazole-containing conditions showed similar reaction to natural infection, while the use of liposomal Amphotericin B significantly decreased the inflammatory response. Chemokines (notably CCL20 and CXCL2) and pro-inflammatory cytokines (IL1A, IL1B, IL23, G-CSF) exhibited the most pronounced differences across antifungals. Pattern recognition receptors and adaptor protein transcription were minimally affected. Protein–protein-interaction network analysis showed that IL23A played a dominant role in upregulated genes. Pathway enrichment analysis indicated that cytokine-cytokine receptor integration, TNF signaling pathways and Toll-like receptor pathways were highly involved. This exploratory study confirms the heterogeneous immunomodulatory role of antifungals. Overall, voriconazole appears to maintain an early pro-inflammatory response seen in natural infection. Assessment of immunomodulatory response with clinical response may provide a better rationale for differences observed across antifungals.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 76%

Section: Discussioncontrasting

confidence: 44%

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Antifungals influence the immune-related transcriptomic landscape of human monocytes after Aspergillus fumigatus infection

Henry

Klement

Gohir

et al. 2022

Sci Rep

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“…Eryptosis might further promote the release of pro-inflammatory cytokines [76], which may in turn contribute to the in vivo toxicity of amphotericin B [77]. Amphotericin B stimulates cyokine release further by stimulation of gene expression in nucleated cells [78].…”

Section: Discussionmentioning

confidence: 99%

Triggering of Suicidal Erythrocyte Death by Amphotericin B

Mahmud

Mauro

Qadri

et al. 2009

Cell Physiol Biochem

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Amphotericin B is widely used as antifungal drug. Side effects include anemia. A variety of drugs and diseases associated with anemia has recently been shown to trigger suicidal erythrocyte death or eryptosis, i.e. cell membrane scrambling and cell shrinkage. Eryptosis may be triggered by increased cytosolic Ca²⁺ activity and by lack of ATP. The present study explored whether amphotericin B stimulates eryptosis. Cell membrane scrambling was estimated from annexin V-binding to phosphatidylserine exposed at the cell surface, cell shrinkage from forward scatter in FACS analysis, cytosolic Ca²⁺ activity from Fluo3 fluorescence and the cytosolic ATP concentration from a luciferase-based assay. Exposure to amphotericin B (0.1 - 1 μg/ml) within 48 hours significantly increased annexin V-binding, decreased forward scatter, increased cytosolic Ca²⁺ activity and decreased cytosolic ATP content. In conclusion, amphotericin B stimulates suicidal cell death of erythrocytes, which may in turn contribute to the clearance of circulating erythrocytes and thus to anemia.

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Immunomodulatory Properties of Antifungal Agents on Immune Functions of the Host

Simitsopoulou

Roilides

2019

Principles and Practice of Transplant Infectious Diseases

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

Cited by 6 publications

References 17 publications

Antifungals influence the immune-related transcriptomic landscape of human monocytes after Aspergillus fumigatus infection

Antifungals influence the immune-related transcriptomic landscape of human monocytes after Aspergillus fumigatus infection

Triggering of Suicidal Erythrocyte Death by Amphotericin B

Immunomodulatory Properties of Antifungal Agents on Immune Functions of the Host

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