Elevated expression of toll-like receptor 4 is associated with NADPH oxidase-induced oxidative stress in B cells of children with autism

AbstractModified LDL-induced inflammation and oxidative stress are involved in the pathogenesis of diabetic retinopathy. Recent studies have also shown that modified LDL activates Toll-like receptor 4 (TLR4) to mediate retinal injury. However, the mechanism by which modified LDL activates TLR4 and the potential role of the TLR4 coreceptor myeloid differentiation protein 2 (MD2) are not known. In this study, we inhibited MD2 with the chalcone derivatives L2H17 and L6H21 and showed that MD2 blockade protected retinal Müller cells against highly oxidized glycated-LDL (HOG-LDL)-induced oxidative stress, inflammation, and apoptosis. MD2 inhibition reduced oxidative stress by suppressing NADPH oxidase-4 (NOX4). Importantly, HOG-LDL activated TLR4 and increased the interaction between NOX4 and TLR4. MD2 was required for the activation of these pathways, as inhibiting MD2 prevented the association of NOX4 with TLR4 and reduced NOX4-mediated reactive oxygen species production and TLR4-mediated inflammatory factor production. Furthermore, treatment of diabetic mice with L2H17 significantly reduced LDL extravasation in the retina and prevented retinal dysfunction and apoptosis by suppressing the TLR4/MD2 pathway. Our findings provide evidence that MD2 plays a critical role in mediating modified LDL-induced cell injury in the retina and suggest that targeting MD2 may be a potential therapeutic strategy.

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Faculty Opinions recommendation of Toll-like receptor 4-activated B cells out-compete Toll-like receptor 9-activated B cells to establish peripheral immunological tolerance.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.716747955.792103216 ◽

2012 ◽

Author(s):

John Cambier ◽

Thomas Packard

Keyword(s):

B Cells ◽

Immunological Tolerance ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Activated B Cells

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Abrogation of Toll-Like Receptor 4 Mitigates Obesity-Induced Oxidative Stress, Proinflammation, and Insulin Resistance Through Metabolic Reprogramming of Mitochondria in Adipose Tissue

Antioxidants and Redox Signaling ◽

10.1089/ars.2019.7737 ◽

2020 ◽

Vol 33 (2) ◽

pp. 66-86 ◽

Cited By ~ 2

Author(s):

Hung-Yu Lin ◽

Shao-Wen Weng ◽

Feng-Chih Shen ◽

Yen-Hsiang Chang ◽

Wei-Shiung Lian ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Adipose Tissue ◽

Metabolic Reprogramming ◽

Toll Like Receptor ◽

Toll Like Receptor 4

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Cateslytin abrogates lipopolysaccharide-induced cardiomyocyte injury by reducing inflammation and oxidative stress through toll like receptor 4 interaction

International Immunopharmacology ◽

10.1016/j.intimp.2021.107487 ◽

2021 ◽

Vol 94 ◽

pp. 107487

Author(s):

Carmine Rocca ◽

Anna De Bartolo ◽

Fedora Grande ◽

Bruno Rizzuti ◽

Teresa Pasqua ◽

...

Keyword(s):

Oxidative Stress ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

And Oxidative Stress

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Soyasaponin Bb inhibits the recruitment of toll-like receptor 4 (TLR4) into lipid rafts and its signaling pathway by suppressing the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent generation of reactive oxygen species

Molecular Nutrition & Food Research ◽

10.1002/mnfr.201600015 ◽

2016 ◽

Vol 60 (7) ◽

pp. 1532-1543 ◽

Cited By ~ 12

Author(s):

Yajie Zhang ◽

Fengping Chen ◽

Jiading Chen ◽

Suqun Huang ◽

Junbin Chen ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Nadph Oxidase ◽

Signaling Pathway ◽

Lipid Rafts ◽

Nicotinamide Adenine Dinucleotide ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Nicotinamide Adenine ◽

Oxygen Species ◽

Toll Like Receptor ◽

Toll Like Receptor 4

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Aerobic Training Down-Regulates Pentraxin 3 and Pentraxin 3/Toll-Like Receptor 4 Ratio, Irrespective of Oxidative Stress Response, in Elderly Subjects

Antioxidants ◽

10.3390/antiox9020110 ◽

2020 ◽

Vol 9 (2) ◽

pp. 110

Author(s):

Brisamar Estébanez ◽

Alexandra L. Rodriguez ◽

Nishant P. Visavadiya ◽

Michael Whitehurst ◽

María J. Cuevas ◽

...

Keyword(s):

Oxidative Stress ◽

Aerobic Training ◽

Oxidative Stress Response ◽

Pentraxin 3 ◽

Elderly Adults ◽

Nitrogen Species ◽

Toll Like Receptor ◽

Oxidative Stress Biomarkers ◽

Toll Like Receptor 4 ◽

Stress Biomarkers

Reactive oxygen and nitrogen species-mediated cellular aging has been linked to diseases such as atherothrombosis and cancer. Although pentraxin 3 (PTX3) is associated with aging-related diseases via TLR4-dependent anti-inflammatory effects, its relationship with oxidative stress in aging remains to be elucidated. Exercise is proposed as the key intervention for health maintenance in the elderly. This study aimed to examine the association of PTX3 levels with changes in oxidative stress in both plasma and peripheral blood mononuclear cells (PBMCs), following aerobic training in elderly adults. Nine trained and five controls participated in an eight-week aerobic training protocol. Enzyme-linked immunosorbent assay (ELISA) and Western blot analyses were used to determine PTX3, toll-like receptor 4 (TLR4), and levels of oxidative stress biomarkers [3-nitrotyrosine (3NT), 4-hydroxynonenal (4-HNE), glutathione (GSH), protein carbonyl (PC), reactive oxygen/ nitrogen species (ROS/RNS), and trolox equivalent antioxidant capacity (TEAC)] in plasma and/or PBMCs. Results showed a down-regulation of PTX3 expression in PBMCs following aerobic training, along with decreased PTX3/TLR4 ratios. Oxidative stress responses in PBMCs remained unchanged with the exercise protocol. Comparable levels of plasma PTX3 and oxidative stress biomarkers were observed in trained vs. control groups. No correlation was found between PTX3 and any oxidative stress biomarkers following training. These findings demonstrated the down-regulation of PTX3 and PTX3/TLR4 ratio, irrespective of oxidative stress response, in elderly adults following eight weeks of aerobic training.

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