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Tacrolimus interacts with voriconazole to reduce the severity of fungal keratitis by suppressing IFN-related inflammatory responses and concomitant FK506 and voriconazole treatment suppresses fungal keratitis
- Source :
- Molecular Vision
- Publication Year :
- 2017
-
Abstract
- Purpose To investigate the expression and roles of type I and II interferons (IFNs) in fungal keratitis, as well as the therapeutic effects of tacrolimus (FK506) and voriconazole on this condition. Methods The mRNA and protein expression levels of type I (IFN-α/β) and II (IFN-γ) IFNs, as well as of related downstream inflammatory cytokines (interleukin (IL)-1α, IL-6, IL-12, and IL-17), were detected in macrophages, neutrophils, lymphocytes, and corneal epithelial cells (A6(1) cells) stimulated with zymosan (10 mg/ml) for 8 or 24 h. A fungal keratitis mouse model was generated through intrastromal injection of Aspergillus fumigatus, and the mice were then divided into four groups: group I, the PBS group; group II, the voriconazole group; group III, the FK506 group; and group IV, the voriconazole plus 0.05% FK506 group. Corneal damage was evaluated with clinical scoring and histological examination. In addition, the mRNA and protein expression levels of type I (IFN-α/β) and type II (IFN-γ) IFNs, as well as related inflammatory cytokines, were determined at different time points using quantitative real-time PCR (qRT-PCR) and western blotting. Results After zymosan stimulation of mouse neutrophils, lymphocytes, macrophages, and A6(1) cells, the IFN mRNA and protein expression levels were markedly increased until 24 h, peaking at 8 h (p
- Subjects :
- Keratitis
Antifungal Agents
Neutrophils
Aspergillus fumigatus
Interleukins
Macrophages
Zymosan
Drug Synergism
Epithelial Cells
Severity of Illness Index
Tacrolimus
Cornea
Mice, Inbred C57BL
Disease Models, Animal
Drug Combinations
Mice
Gene Expression Regulation
Animals
Aspergillosis
Female
Interferons
Lymphocytes
Voriconazole
Eye Infections, Fungal
Research Article
Subjects
Details
- ISSN :
- 10900535
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Molecular vision
- Accession number :
- edsair.pmid..........8c659ccf6a2e62df04bc5bb296682b5c