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Nerve growth factor inhibits TLR3-induced inflammatory cascades in human corneal epithelial cells.

ABSTRACT: Background:In herpes simplex epithelial keratitis, excessive TLR3-induced cellular responses after virus infection evoke inflammatory cascades that might be destructive to the host cornea. Nerve growth factor (NGF), a pluripotent neurotrophic factor with immune regulatory effect, was proved to be effective in Herpes simplex keratitis (HSK) treatment, although the detailed mechanisms remain unclear. This study aims to investigate the effects of NGF on modulating inflammatory responses triggered by TLR3 activation in human corneal epithelial cells (HCECs) in vitro. Methods:HCECs were stimulated with TLR3 agonist, poly(I:C), in the absence or presence of NGF. Cell viability and cytotoxicity were measured by a CCK-8 assay and LDH release assay, respectively. The activation of NF-?B signaling pathway was examined using immunofluorescence staining and western blotting. Levels of proinflammatory cytokines were determined by ELISA or RT-qPCR. ROS generation and 8-OHdG positive cells were examined by a fluorometric analysis. Results:It was shown that NGF significantly inhibited the generation of proinflammatory cytokines in HCECs triggered by TLR3 activation (P?

SUBMITTER: Chen H

PROVIDER: S-EPMC6933932 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Nerve growth factor inhibits TLR3-induced inflammatory cascades in human corneal epithelial cells.

Chen Huiyu H Zhang Jing J Dai Yiqin Y Xu Jianjiang J

Journal of inflammation (London, England) 20191226

<h4>Background</h4>In herpes simplex epithelial keratitis, excessive TLR3-induced cellular responses after virus infection evoke inflammatory cascades that might be destructive to the host cornea. Nerve growth factor (NGF), a pluripotent neurotrophic factor with immune regulatory effect, was proved to be effective in Herpes simplex keratitis (HSK) treatment, although the detailed mechanisms remain unclear. This study aims to investigate the effects of NGF on modulating inflammatory responses tri ...[more]

PMID: 31889912

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Project description:Neurotrophic Keratopathy (NK) is a neurodegenerative corneal disease that results in diminished corneal sensation. Previous studies have found that Cenegermin 0.002%, a recombinant human nerve growth factor (rhNGF), improves corneal epithelial healing in stage 2 and 3 NK patients. However, rhNGF effect on corneal sensation and nerve regeneration has not been well established. Thus, this study aims to analyze the effect of rhNGF on corneal nerve regeneration using in vivo confocal microscopy (IVCM) and on corneal sensitivity in NK patients. This is a retrospective, longitudinal, case-control study that included patients with NK, treated with rhNGF for at least 4 weeks, with pre- and post-treatment IVCM images available for analysis. Chart reviews were conducted documenting prior medical and surgical history, clinical signs and symptoms, and corneal sensation using Cochet-Bonnet esthesiometry. Corneal nerve parameters were assessed by IVCM. Sex- and age-matched reference controls were selected from a database of healthy subjects for comparison. The study included 25 patients, with 22 (88%) stage 1, two (8%) stage 2, and 1 (4%) stage 3 NK patients, with a median age of 64 years (range: 30-93 years). Total, main, and branch nerve densities [median (range) in mm/mm2] were lower in the NK group pre-treatment [2.3 (0.0-21.1); 1.7 (0.0-13.0); 0.5 (0.0-10.2); respectively] vs. controls [22.3 (14.9-29.0); 10.1 (3.2-15.4); and 12.1 (6.2-18.4), (p < 0.0001 for all), respectively]. Post-treatment nerve densities increased compared to pre-treatment to 5.3 (0.0-19.4, p = 0.0083) for total, 3.5 (0.0-13.2, p = 0.0059) for main, and 2.0 (0.0-10.4, p = 0.0251) for branch nerves, but remained lower than controls (p < 0.0001 for all). Corneal sensation increased from 2.3 ± 1.1 cm pre-treatment to 4.1 ± 1.4 cm post-treatment (p = 0.001). Median best corrected visual acuity significantly increased following rhNGF treatment from 0.4 (0.0-1.6) to 0.12 (-0.1 to 1.6) (p = 0.007). Patients with NK treated with at least 4 weeks of rhNGF, showed a significant increase in corneal nerve densities after treatment. A significant increase in corneal sensation, as well as best corrected visual acuity, was observed following treatment.

Dataset Information

Nerve growth factor inhibits TLR3-induced inflammatory cascades in human corneal epithelial cells.

Publications

Nerve growth factor inhibits TLR3-induced inflammatory cascades in human corneal epithelial cells.

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