Back to Search
Start Over
Chelerythrine ameliorates Aspergillus fumigatus keratitis through suppressing the LOX-1/p38 MAPK signaling pathway.
- Source :
-
Cytokine [Cytokine] 2024 Oct; Vol. 182, pp. 156717. Date of Electronic Publication: 2024 Jul 26. - Publication Year :
- 2024
-
Abstract
- Purpose: Aspergillus fumigatus (A. fumigatus) keratitis is a type of infectious corneal disease that significantly impairs vision. The objective of this study is to evaluate the therapeutic potential of chelerythrine (CHE) on A. fumigatus keratitis.<br />Methods: The antifungal activity of CHE was assessed through various tests including the minimum inhibitory concentration test, scanning electron microscopy, transmission electron microscopy, propidium iodide uptake test and plate count. Neutrophil infiltration and activity were assessed using immunofluorescence staining and the myeloperoxidase test. RT-PCR, western blotting assay, and ELISA were performed to measure the expression levels of proinflammatory cytokines (IL-1β and IL-6), NF-E2-related factor (Nrf2), heme oxygenase-1 (HO-1), and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), as well as to determine the ratio of phosphorylated-p38 (p-p38) mitogen-activated protein kinase (MAPK) to p38 MAPK.<br />Results: In vitro, CHE inhibited the growth of A. fumigatus conidia, reduced fungal hyphae survival, and prevented fungal biofilm formation. In vivo, CHE reduced the severity of A. fumigatus keratitis and exhibited an excellent anti-inflammatory effect by blocking neutrophil infiltration. Furthermore, CHE decreased the expression levels of proinflammatory cytokines and LOX-1 at both mRNA and protein levels, while also decreasing the p-p38 MAPK/p38 MAPK ratio. Additionally, CHE increased the expression levels of Nrf2 and HO-1.<br />Conclusion: CHE provides protection against A. fumigatus keratitis through multiple mechanisms, including reducing fungal survival, inducing anti-inflammatory effects, enhancing Nrf2 and HO-1 expression, and suppressing the signaling pathway of LOX-1/p38 MAPK.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Mice
Heme Oxygenase-1 metabolism
Signal Transduction drug effects
MAP Kinase Signaling System drug effects
Antifungal Agents pharmacology
Antifungal Agents therapeutic use
Female
Cytokines metabolism
Aspergillus fumigatus drug effects
Scavenger Receptors, Class E metabolism
p38 Mitogen-Activated Protein Kinases metabolism
Keratitis microbiology
Keratitis drug therapy
Keratitis metabolism
Benzophenanthridines pharmacology
Benzophenanthridines therapeutic use
NF-E2-Related Factor 2 metabolism
Aspergillosis drug therapy
Aspergillosis microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0023
- Volume :
- 182
- Database :
- MEDLINE
- Journal :
- Cytokine
- Publication Type :
- Academic Journal
- Accession number :
- 39067394
- Full Text :
- https://doi.org/10.1016/j.cyto.2024.156717