The role of LOX-1 on innate immunity against Aspergillus keratitis in mice

He, Kun; Yue, Li-hui; Zhao, Guiqiu; Cui, Li; Lin, Jing; Jiang, Nan; Wang, Qian; Xu, Qiang; Peng, Xudong; Hu, Liting; Zhang, Jie

doi:10.18240/ijo.2016.09.01

Cited by 16 publications

(9 citation statements)

References 23 publications

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“…Our previous studies have shown several inflammation-related factors were upregulated in A fumigatus infected mice, such as LOX-1, TNF-α, and IL-6. 38 – 40 In this study, high expression of SREC-Ⅰ mRNA level was also detected in mouse corneal epithelium after A fumigatus infection and peaked at 12 hours, whereas the protein expression increased at 48 hours p.i., which was remarkably suppressed by an SREC-Ⅰ–neutralizing antibody. In agreement with the decreased protein expression of SREC-Ⅰ, the SREC-Ⅰ mRNA level was also downregulated after anti–SREC-Ⅰ antibody treatment in mice.…”

Section: Discussionsupporting

confidence: 52%

The Role of SREC-Ⅰ in Innate Immunity to Aspergillus fumigatus Keratitis

Zhang

Peng

Lin

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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To determine the role of scavenger receptor expressed by endothelial cell-1 (SREC-Ⅰ) in vitro and in a mouse model of Aspergillus fumigatus keratitis.METHODS. SREC-Ⅰ mRNA and protein expression were tested in both normal and A fumigatus stimulated human corneal epithelial cells (HCECs). Immunofluorescence was used to detect SREC-Ⅰ expression in human corneas with or without A fumigatus infection. HCECs were incubated with SREC-Ⅰ small interfering RNA, then the mRNA levels of LOX-1, IL-1β, and TNF-α were detected after A fumigatus stimulation. A mouse fungal keratitis (FK) model was established and SREC-Ⅰ mRNA and protein expression were detected by RT-PCR, Western blot and immunofluorescence. The severity of FK was evaluated by clinical score. CLCX1, LOX-1, IL-1β, and TNF-α mRNA expression levels were tested before and after anti-SREC-Ⅰ treatment. RESULTS. SREC-Ⅰ expressed in normal andA fumigatus treated HCECs and human corneal epithelium. In vitro experiment showed that SREC-Ⅰ mRNA and protein levels were significantly increased after A fumigatus stimulation. SREC-Ⅰ small interfering RNA treatment inhibited the expressions of LOX-1, IL-1β, and TNF-α in HCECs. The expressions of CLCX1, LOX-1, IL-1β, and TNF-α were elevated in mice with A fumigatus keratitis, which could be decreased by SREC-Ⅰ-neutralizing antibody treatment.CONCLUSIONS. SREC-Ⅰ is a key mediator in inflammatory response induced by A fumigatus keratitis. SREC-Ⅰ blockade could be a potential therapeutic approach for FK.

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Section: Discussionsupporting

confidence: 52%

The Role of SREC-Ⅰ in Innate Immunity to Aspergillus fumigatus Keratitis

Zhang

Peng

Lin

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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“…It was demonstrated for the first time that LOX-1 in both HUVECs (Figures 2A,C) and THP-1 cells (Figures 2B,D) could be activated by the periodontal pathogen P. gingivalis. Previous studies have reported that LOX-1 recognized some pathogens such as S. aureus, E. coli (Shimaoka et al, 2001), C. pneumoniae (Campbell et al, 2013) and Aspergillus (He et al, 2016). However, no studies have focused on the response of LOX-1 to P. gingivalis.…”

Section: Discussionmentioning

confidence: 99%

LOX-1 Regulates P. gingivalis-Induced Monocyte Migration and Adhesion to Human Umbilical Vein Endothelial Cells

Liu

et al. 2020

Front. Cell Dev. Biol.

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Porphyromonas gingivalis (P. gingivalis) is one of the main periodontal bacteria. This pathogen was reported to enhance monocyte migration and adhesion to endothelial cells in atherosclerosis. The scavenger receptor lectin-like oxidized lowdensity lipoprotein receptor-1 (LOX-1) plays a pivotal role in atherogenesis. The aim of this study was to investigate whether LOX-1 modulates P. gingivalis-mediated monocyte migration and adhesion to endothelial cells and how it works. The results showed that the migration and adhesion of monocytic THP-1 cells to human umbilical vein endothelial cells (HUVECs) were significantly enhanced when HUVECs or THP-1 cells were challenged with P. gingivalis. Meanwhile, the expression level of LOX-1 in both HUVECs and THP-1 cells were also significantly increased by P. gingivalis stimulation. It is well known that ligand/receptor pairs monocyte chemoattractant protein-1 (MCP-1)/CC chemokine receptor 2 (CCR2), selectins/Integrins, and cell adhesion molecules (CAMs)/Integrins mediate monocyte migration and adhesion to endothelial cells. In this study, LOX-1 was demonstrated to be crucially involved in P. gingivalis-induced THP-1 cell migration and adhesion to HUVECs, by regulating expression of ligands MCP-1, intercellular adhesion molecule-1 (ICAM-1) and E-selectin in HUVECs and that of their receptors CCR2 and Integrin αMβ2 in THP-1 cells. The nuclear factor-kappa B (NF-κB) signaling pathway was proved to be involved in this process. In conclusion, LOX-1 plays a crucial role in P. gingivalis-induced monocyte migration and adhesion to endothelial cells. This result implies LOX-1 may act as a bridge in linking periodontitis to atherosclerosis.

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“…Previous studies have shown that LOX-1 is an important pattern recognition receptor involved in corneal antifungal immune responses(22). Inhibition of LOX-1 results in the lower intracellular ROS production, p38-MAPK dephosphorylation, NF-κB translocation and aberrant BCl-2 expression, and down-regulate inflammation together(53). All results suggested that the down-regulated inflammatory response was associated with the decreased LOX-1 signaling.…”

Section: Discussionmentioning

confidence: 99%

Hinokitiol alters Gene Expression in Aspergillus fumigatus, protects against fungal keratitis by Reducing Fungal Load, LOX-1, Proinflammatory cytokines and Neutrophil Infiltration

Lin

Peng

et al. 2022

Preprint

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Hinokitiol (HK), a tropolone-related compound found in cupressaceous plants, has antifungal and anti-inflammatory properties. But its roles in Aspergillus fumigatus (A.F.) keratitis remains unknown. This study examined the antifungal activity of HK against A.F. and investigated its possible mechanisms at the ultrastructural and transcriptional levels. We tested the minimum inhibitory concentration (MIC) of HK against A.F. Our data showed that the MIC50 was 2 μg/ml and MIC90 was 8 μg/ml, and HK could significantly inhibit the spore germination and mycelial growth of A.F. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations showed that HK induced significant changes in hyphal morphology and microstructure, including cell membrane rupture and intracellular structural disorder. Adhesion assay and biofilm assay experiments showed that HK reduced the adhesion of spores to human corneal epithelial cells (HCECs) and inhibited the formation of biofilms. Th genetic changes of A.F. after HK treatment were analyzed by RNA sequencing, and a total of 2487 differentially expressed genes (DEGs) were identified, including the down-regulated DEGs related to carbohydrate and various amino acid metabolism, ribosome biogenesis, asexual reproduction, and up-regulated DEGs related to steroid biosynthesis through GO and KEGG enrichment analysis. RNA-seq results suggested that HK may play an antifungal effect by destroying the structural integrity of its wall and membrane, inhibiting protein biosynthesis and the growth and reproduction of A.F .10 μg/ml HK, which had no effect on proliferation and migration of HCECs, was used in the treatment of murine fungal keratitis (FK). We found that HK eyedrop treatment could reduce the severity of FK by reducing corneal fungal burden, neutrophil infiltration, and the expression of LOX-1 and pro-inflammatory factors. HK is expected to be a safe and effective new drug for FK treatment.

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The role of LOX-1 on innate immunity against Aspergillus keratitis in mice

Abstract: The expression of LOX-1 can affect the expression of pro-inflammatory and anti-inflammatory cytokines in fungal infected corneas, macrophages and neutrophils of C57BL/6. LOX-1 inhibition rebalances the inflammatory response of fungal keratitis in mice.

Cited by 16 publications

References 23 publications

The Role of SREC-Ⅰ in Innate Immunity to Aspergillus fumigatus Keratitis

The Role of SREC-Ⅰ in Innate Immunity to Aspergillus fumigatus Keratitis

LOX-1 Regulates P. gingivalis-Induced Monocyte Migration and Adhesion to Human Umbilical Vein Endothelial Cells

Hinokitiol alters Gene Expression in Aspergillus fumigatus, protects against fungal keratitis by Reducing Fungal Load, LOX-1, Proinflammatory cytokines and Neutrophil Infiltration

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