IL-36α Exerts Proinflammatory Effects in A<i>spergillus fumigatus</i> Keratitis of Mice Through the Pathway of IL-36α/IL-36R/NF-κB

Niu, Yawen; Ren, Changjie; Peng, Xudong; Li, Cui; Xu, Qiang; Hu, Liting; Zhang, Ziyue; Zhao, Guiqiu; Lin, Jing

doi:10.1167/iovs.62.4.16

Cited by 11 publications

(8 citation statements)

References 28 publications

(29 reference statements)

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“… 33 Recent evidence suggests that the NF-κB pathway is activated in murine Aspergillus fumigatus keratitis. 15 , 34 However, the upstream regulators of the NF-κB pathway in FK remain obscure. Notably, our study found that the expression of inflammatory factors was elevated and that the NF-κB pathway was activated in FK.…”

Section: Discussionmentioning

confidence: 99%

“…The nuclear factor kappa B (NF-κB) signaling pathway is typically involved in inflammatory response and plays an indispensable role in the physiological and pathological mechanisms of infectious keratitis. 14 , 15 However, the upstream regulator of the NF-κB signaling pathway in FK remains elusive. Recent research has demonstrated that METTL3 can modulate the inflammatory response in macrophages via the NF-κB signaling pathway in rheumatoid arthritis.…”

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confidence: 99%

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Inhibition of the m6A Methyltransferase METTL3 Attenuates the Inflammatory Response inFusarium solani-Induced Keratitis via the NF-κB Signaling Pathway

Tang

Huang

2022

Invest. Ophthalmol. Vis. Sci.

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Purpose The purpose of this study was to elucidate the effect of methyltransferase-like enzyme 3 (METTL3) on inflammation and the NF-κB signaling pathway in fungal keratitis (FK). Methods We established corneal stromal cell models and FK mouse models by incubation with Fusarium solani . The overall RNA N6-methyladenosine (m6A) level was determined using an m6A RNA methylation assay kit. The expression of METTL3 was quantified via real-time quantitative polymerase chain reaction (RT–PCR), Western blotting, and immunofluorescence. Subsequently, the level of tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) was identified by Western blotting and immunofluorescence. Moreover, we assessed the effect of METTL3 by transfecting cells with siRNA (in vitro) or adeno-associated virus (in vivo). Hematoxylin and eosin (H&E) staining and slit-lamp biomicroscopy were performed to evaluate corneal damage. Furthermore, the state of NF-κB signaling pathway activation was examined by Western blotting. In addition, RT–PCR and enzyme-linked immunosorbent assays (ELISAs) were performed to evaluate levels of the pro-inflammatory factors interleukin-1 β (IL-1 β ), interleukin-6 (IL-6) and TNF- ɑ . Results Our data demonstrated that the levels of the RNA m6A methylation and METTL3 were dramatically increased and that the NF-κB signaling pathway was activated in Fusarium solani -induced keratitis. Inhibition of METTL3 decreased the level of TRAF6, downregulated the phospho-p65(p-p65)/p65 and phospho-IκB(p-IκB)/IκB protein ratios, simultaneously attenuating the inflammatory response and fungal burden in FK. Conclusions Our research suggests that the m6A methyltransferase METTL3 regulates the inflammatory response in FK by modulating the NF-κB signaling pathway.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Inhibition of the m6A Methyltransferase METTL3 Attenuates the Inflammatory Response inFusarium solani-Induced Keratitis via the NF-κB Signaling Pathway

Tang

Huang

2022

Invest. Ophthalmol. Vis. Sci.

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“…All the experiments were repeated three times. 48 MPO assay. To determine the activity of polymorphonuclear neutrophils, corneas were harvested at 3 days p.i.…”

Section: Assessment Of the Antifungal Efficiency Of Ocs In Vitromentioning

confidence: 99%

Oxidized chondroitin sulfate eye drops ameliorate the prognosis of fungal keratitis with anti-inflammatory and antifungal effects

et al. 2022

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“…The inflammatory response can be initiated by macrophages via the release of proinflammatory cytokines. Therefore, macrophages can phagocytose and kill specific pathogens [ 54 ]. The phagocytosis of macrophages can be adjusted by miRNAs to moderate the clearance of the pathogen.…”

Section: Introductionmentioning

confidence: 99%

The current landscape of microRNAs (miRNAs) in bacterial pneumonia: opportunities and challenges

2022

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MicroRNAs (miRNAs), which were initially discovered in Caenorhabditis elegans, can regulate gene expression by recognizing cognate sequences and interfering with the transcriptional or translational machinery. The application of bioinformatics tools for structural analysis and target prediction has largely driven the investigation of certain miRNAs. Notably, it has been found that certain miRNAs which are widely involved in the inflammatory response and immune regulation are closely associated with the occurrence, development, and outcome of bacterial pneumonia. It has been shown that certain miRNA techniques can be used to identify related targets and explore associated signal transduction pathways. This enhances the understanding of bacterial pneumonia, notably for “refractory” or drug-resistant bacterial pneumonia. Although these miRNA-based methods may provide a basis for the clinical diagnosis and treatment of this disease, they still face various challenges, such as low sensitivity, poor specificity, low silencing efficiency, off-target effects, and toxic reactions. The opportunities and challenges of these methods have been completely reviewed, notably in bacterial pneumonia. With the continuous improvement of the current technology, the miRNA-based methods may surmount the aforementioned limitations, providing promising support for the clinical diagnosis and treatment of “refractory” or drug-resistant bacterial pneumonia.

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IL-36α Exerts Proinflammatory Effects in Aspergillus fumigatus Keratitis of Mice Through the Pathway of IL-36α/IL-36R/NF-κB

Abstract: IL-36α exerts proinflammatory effects in Aspergillus fumigatus keratitis of mice through the pathway of IL-36α/IL-36R/NF-κB.

Cited by 11 publications

References 28 publications

Inhibition of the m6A Methyltransferase METTL3 Attenuates the Inflammatory Response inFusarium solani-Induced Keratitis via the NF-κB Signaling Pathway

Inhibition of the m6A Methyltransferase METTL3 Attenuates the Inflammatory Response inFusarium solani-Induced Keratitis via the NF-κB Signaling Pathway

Oxidized chondroitin sulfate eye drops ameliorate the prognosis of fungal keratitis with anti-inflammatory and antifungal effects

The current landscape of microRNAs (miRNAs) in bacterial pneumonia: opportunities and challenges

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