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

Abstract

BackgroundIn 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.MethodsHCECs 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-κB 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.ResultsIt was shown that NGF significantly inhibited the generation of proinflammatory cytokines in HCECs triggered by TLR3 activation (P < 0.05), probably via suppressing NF-κB activation. NGF also impeded the upstream signal to initiate NF-κB activation by scavenging ROS by approximately 50% (P < 0.05). In addition, 8-OHdG positive cells were substantially attenuated by NGF treatment (P < 0.01).ConclusionsTaken together, this study indicates that NGF could inhibit TLR3-induced inflammatory cascades in HCECs, suggesting NGF as a potential therapeutic agent for HSK.

Bone Marrow Mesenchymal Stem Cells Promote Remyelination in Spinal Cord by Driving Oligodendrocyte Progenitor Cell Differentiation Via Tnfα/Relb-Hes1 Pathway: A Rat Model Study of 2,5-Hexanedione-Induced Neurotoxicity

“…NGF binds to its receptor TrkA and drives neuron survival and neurite outgrowth via PI3K/Akt and Ras/MAPK signaling, respectively. Investigations by other groups also demonstrated that NGF could dampen in ammatory response via downregulating proin ammatory cytokines including TNFα [48,49] Our study found that NGF inhibited TNFα expression and such inhibitory effect was abolished by NGF neutralizing antibody or TrkA inhibitor. These results imply that NGF secreted by BMSCs inhibited TNFα/RelB pathway and induced remyelination, in consistence with the results of other groups [48,50].…”

Bone marrow mesenchymal stem cells promote remyelination in spinal cord by driving oligodendrocyte progenitor cell differentiation via TNFα/RelB-Hes1 pathway: a rat model study of 2,5-hexanedione-induced neurotoxicity

“…NGF binds to its receptor TrkA and drives neuron survival and neurite outgrowth via PI3K/Akt and Ras/MAPK signaling, respectively. Investigations by other groups also demonstrated that NGF could dampen inflammatory response via downregulating proinflammatory cytokines including TNFα [ 56 , 57 ]. Our study found that NGF inhibited TNFα expression and such inhibitory effect was abolished by NGF neutralizing antibody or TrkA inhibitor.…”

1,25-Dihydroxyvitamin D3 attenuates IL-1β secretion by suppressing NLRP1 inflammasome activation by upregulating the NRF2-HO-1 pathway in epidermal keratinocytes

“…Reins et al [ 35 ] have shown that in epithelial cells, 1,25(OH) 2 VD 3 inhibited poly(I:C)-induced IL-1β secretion. Because ROS production is involved in poly(I:C)-proinflammatory action [ 36 ], NRF2-HO-1 axis activation by 1,25(OH) 2 VD 3 partly explain why 1,25(OH) 2 VD 3 inhibits poly(I:C)-induced IL-1β secretion in epithelial cells.…”