Superoxide Dismutase 3 Suppresses Hyaluronic Acid Fragments Mediated Skin Inflammation by Inhibition of Toll-Like Receptor 4 Signaling Pathway: Superoxide Dismutase 3 Inhibits Reactive Oxygen Species-Induced Trafficking of Toll-Like Receptor 4 to Lipid Rafts

Sulfur dioxide (SO2) is a common air pollutant that can exacerbate asthmatic airway inflammation. The mechanisms underlying these effects are not yet fully understood. In this study, we investigated the effects of SO2 exposure (10 mg/m3) on asthmatic airway inflammation in ovalbumin-induced asthmatic mice. Our results showed that SO2 exposure alone induced slight airway injury, decreased superoxide dismutase activity, and increased nuclear factor-κB (NF-κB) expression in the lungs of mice. Moreover, SO2 exposure in asthmatic mice induced marked pathological damage, significantly increased the counts of inflammatory cells (e.g., macrophages, lymphocytes, and eosinophils) in bronchoalveolar lavage fluid, and significantly enhanced malondialdehyde and glutathione levels in the lungs. Moreover, the expression of toll-like receptor 4 (TLR4), NF-κB, pro-inflammatory cytokines (e.g., tumor necrosis factor α and interleukin-6), and type II T-helper cell (Th2) cytokines was found to be elevated in the mice exposed to SO2 and ovalbumin compared to those exposed to ovalbumin alone. These results suggest that SO2 amplifies Th2-mediated inflammatory responses, which involve reactive oxygen species and TLR4/NF-κB pathway activation; these can further enhance Th2 cytokine expression and eosinophilic inflammation. Thus, our findings provide important evidence to understand a potential mechanism through which SO2 may exacerbate airway asthmatic inflammation.

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Hypoxia Diminishes Toll-Like Receptor 4 Expression Through Reactive Oxygen Species Generated by Mitochondria in Endothelial Cells

The Journal of Immunology ◽

10.4049/jimmunol.169.4.2069 ◽

2002 ◽

Vol 169 (4) ◽

pp. 2069-2075 ◽

Cited By ~ 58

Author(s):

Itaru Ishida ◽

Hiroshi Kubo ◽

Satoshi Suzuki ◽

Tomoko Suzuki ◽

Sachiko Akashi ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Endothelial Cells ◽

Reactive Oxygen ◽

Oxygen Species ◽

Toll Like Receptor ◽

Toll Like Receptor 4

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Dendritic polyglycerols are modulators of microglia-astrocyte crosstalk

Future Neurology ◽

10.2217/fnl-2019-0008 ◽

2019 ◽

Vol 14 (4) ◽

pp. FNL31 ◽

Cited By ~ 4

Author(s):

Dusica Maysinger ◽

Mélanie Lalancette-Hébert ◽

Jeff Ji ◽

Katherine Jabbour ◽

Jens Dernedde ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Transgenic Animals ◽

Luciferase Reporter ◽

Oxygen Species ◽

Toll Like Receptor ◽

Astrocyte Activation ◽

Toll Like Receptor 4 ◽

Primary Mouse ◽

Dendritic Nanostructures

Aim: To determine the ability of sulfated dendritic polyglycerols (dPGS) to modulate neuroglia activation challenged with lipopolysaccharide (LPS). Materials & methods: Microglia/astrocyte activation in vivo was determined in transgenic animals expressing TLR2-/GFAP-luciferase reporter. Mechanisms implicated in microglia-astrocyte crosstalk were studied in primary mouse brain cultures. Results & discussion: dPGS significantly reduced microglia activation in vivo, and decreased astrocytic LCN2 production. Activated microglia are necessary for astrocyte stimulation and increase in LCN2 abundance. LCN2 production in astrocytes involves signaling via toll-like receptor 4, activation of NF-κB, IL6 and enhancement of reactive oxygen species. Conclusion: dPGS are powerful modulators of microglia-astrocyte crosstalk and LCN2 abundance; dPGS are promising anti-inflammatory dendritic nanostructures.

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Toll-like Receptor 4 Is Essential to Preserving Cardiac Function and Survival in Low-grade Polymicrobial Sepsis

Anesthesiology ◽

10.1097/aln.0000000000000337 ◽

2014 ◽

Vol 121 (6) ◽

pp. 1270-1280 ◽

Cited By ~ 14

Author(s):

Ming Zhang ◽

Lin Zou ◽

Yan Feng ◽

Yu-Jung Chen ◽

Qichang Zhou ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen Species Generation ◽

Reactive Oxygen ◽

Polymicrobial Sepsis ◽

Low Grade ◽

Oxygen Species ◽

Toll Like Receptor ◽

Wild Type ◽

Toll Like Receptor 4 ◽

Cecum Ligation

Abstract Background: Toll-like receptor 4 (TLR4), the receptor for endotoxin, mediates hyperinflammatory response and contributes to high mortality during both endotoxin shock and severe sepsis. However, little is known about the role of TLR4 in the pathogenesis of low-grade polymicrobial sepsis, which is often associated with immunosuppression. Methods: Low-grade polymicrobial sepsis was generated by cecum ligation and puncture. Mortality was monitored in wild- type (C57BL/10ScSn) and TLR4def (C57BL/10ScCr) mice. Ex vivo heart and individual cardiomyocyte function were assessed in Langendorff (Hugo Sachs Elektronik; Harvard Apparatus, Holliston, MA) and IonOptix systems (IonOptix, Milton, MA), respectively. Serum chemistry was tested for liver and kidney injury. Cytokines were examined using a multiplex immunoassay. Neutrophil migratory and phagocytic functions were assessed using flow cytometry. Reactive oxygen species were measured using redox-sensitive dichlorodihydrofluorescein dye. Results: Following cecum ligation and puncture, wild-type mice developed bacterial peritonitis with mild cardiac dysfunction (n = 3 in sham and n = 8 in cecum ligation and puncture) and a mortality of 23% within 14 days (n = 22). In comparison, septic TLR4def mice had deleterious cardiac dysfunction (n = 6 in sham and n = 10 in cecum ligation and puncture), kidney and liver injury (n = 7), and much higher mortality at 81% (n = 21). The deleterious effects observed in septic TLR4def mice were associated with increased local and systemic cytokine response, reduced neutrophil migratory and phagocytic function, increased reactive oxygen species generation in leukocytes, and impaired bacterial clearance. Conclusion: TLR4 plays an essential role in host defense against low-grade polymicrobial sepsis by mediating neutrophil migratory/phagocytic functions, attenuating inflammation, reducing reactive oxygen species generation, and enhanced bacterial clearance.

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