期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 63, 期 12, 页码 -出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.63.12.12
关键词
gallic acid (GA); fungal keratitis (FK); antifungal; anti-inflammatory; Nrf2; HO-1
资金
- National Natural Science Foundation of China
- Youth Project of Natural Science Foundation of Shandong Province
- [82101095]
- [82171029]
- [ZR2019BH004]
Gallic acid alleviates Aspergillus fumigatus keratitis severity by inhibiting fungal load, reducing neutrophil infiltration, downregulating pro-inflammatory cytokines expression, and enhancing the Nrf2/HO-1 pathway.
PURPOSE. The purpose of this study was to explore the antifungal and anti-inflammatory effects of gallic acid (GA) on Aspergillus fumigatus (A. fumigatus) keratitis.METHODS. CCK-8 assay and Draize eye test were used to determine the non-cytotoxic concentration of GA in RAW264.7 cells and an A. fumigatus keratitis mouse model. The antifungal effects of GA were analyzed using minimal inhibitory concentration (MIC), biofilm formation test, fungal adherence assay, calcofluor white staining, and propidium iodide staining. The therapeutic effects of GA were estimated by slit lamp photographs, clinical score, hematoxylin and eosin (H&E) staining, and Periodic acid-Schiff staining in vivo. Immunofluorescence staining and myeloperoxidase assay were conducted to iden-tify neutrophil infiltration and activity. RT-PCR, ELISA, and Western blot were performed to detect the expression of pro-inflammatory cytokines and Nrf2/HO-1.RESULTS. In HCECs and A. fumigatus keratitis mouse model, GA at 100 mu g/mL did not affect cell viability, thus this concentration was applied to subsequent experiments. In vitro, GA significantly inhibited A. fumigatus growth, biofilm formation, and adhesion. In vivo, 100 mu g/mL GA alleviated the severity of fungal keratitis (FK) by repressing fungal load, reducing neutrophil infiltration, and lowering MPO activity. Besides, the expression of IL-1 beta, TNF-alpha, LOX-1, and COX-2 was inhibited, whereas Nrf2 and HO-1 expression was enhanced at both mRNA and protein levels in the 100 mu g/mL GA treated group in comparison to PBS control.CONCLUSIONS. GA ameliorates FK severity through inhibiting A. fumigatus load, reducing neutrophils infiltration, downregulating the expression of pro-inflammatory cytokines, and enhancing the Nrf2/HO-1 pathway, which provides new insight into A. fumigatus keratitis treatment.
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