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Chelerythrine ameliorates Aspergillus fumigatus keratitis through suppressing the LOX-1/p38 MAPK signaling pathway.
Liu, Wenyao; Qi, Yinghe; Diao, Weilin; Lin, Jing; Zhang, Lina; Wang, Qian; Gu, Lingwen; Feng, Zhuhui; Chi, Menghui; Wang, Yuwei; Yi, Wendan; Li, Yuqi; Li, Cui; Zhao, Guiqiu.
Afiliação
  • Liu W; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
  • Qi Y; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
  • Diao W; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
  • Lin J; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
  • Zhang L; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
  • Wang Q; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
  • Gu L; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
  • Feng Z; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
  • Chi M; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
  • Wang Y; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
  • Yi W; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
  • Li Y; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
  • Li C; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China. Electronic address: yankelicui@126.com.
  • Zhao G; Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China. Electronic address: zhaoguiqiu_good@126.com.
Cytokine ; 182: 156717, 2024 Oct.
Article em En | MEDLINE | ID: mdl-39067394
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.

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-1ß 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.

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.

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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Aspergilose / Aspergillus fumigatus / Proteínas Quinases p38 Ativadas por Mitógeno / Fator 2 Relacionado a NF-E2 / Receptores Depuradores Classe E / Benzofenantridinas / Ceratite Limite: Animals Idioma: En Revista: Cytokine Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Aspergilose / Aspergillus fumigatus / Proteínas Quinases p38 Ativadas por Mitógeno / Fator 2 Relacionado a NF-E2 / Receptores Depuradores Classe E / Benzofenantridinas / Ceratite Limite: Animals Idioma: En Revista: Cytokine Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China