Macrophage Reporter Cell Assay for Screening Immunopharmacological Activity of Cell Wall-Active Antifungals
| Autor: | Dimitrios P. Kontoyiannis, Russell E. Lewis, Cameron M. Douglas, Katherine Young, Guangling Liao |
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| Přispěvatelé: | R. E. Lewi, G. Liao, K. Young, C. Dougla, D. P. Kontoyiannis |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Antifungal Agents
Cell Microbial Sensitivity Tests Aspergillus fumigatus Microbiology Cell wall Echinocandins Lipopeptides Mice In vivo Caspofungin Cell Wall Candida albicans medicine Animals Pharmacology (medical) Experimental Therapeutics immunopharmacology Glycosides Pharmacology biology Dose-Response Relationship Drug Macrophages NF-kappa B NFKB1 biology.organism_classification Alkaline Phosphatase ANTIFUNGAL COMPOUNDS Corpus albicans Triterpenes Transcription Factor AP-1 Infectious Diseases medicine.anatomical_structure Aminoglycosides Alkaline phosphatase |
| Popis: | Antifungal exposure can elicit immunological effects that contribute to activity in vivo , but this activity is rarely screened in vitro in a fashion analogous to MIC testing. We used RAW 264.7 murine macrophages that express a secreted embryonic alkaline phosphatase (SEAP) gene induced by transcriptional activation of NF-κB and activator protein 1 (AP-1) to develop a screen for immunopharmacological activity of cell wall-active antifungal agents. Isolates of Candida albicans and Aspergillus fumigatus that conditionally express genes involved in cell wall synthesis were also tested with the reporter macrophages. We found that growth of fungi in subinhibitory concentrations of glucan synthesis inhibitors (caspofungin and enfumafungin A) or repression of the β-glucan catalytic subunit of glucan synthase, FKS1 , increased macrophage NF-κB/AP-1 activation in a dectin-1-dependent manner. This pattern of activation was also transiently observed with repression of chitin synthesis in C. albicans or when yeast cells were incubated in low concentrations of the chitin synthesis inhibitor nikkomycin Z. |
| Databáze: | OpenAIRE |
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