scholarly journals Trypanosoma brucei Lipophosphoglycan Induces the Formation of Neutrophil Extracellular Traps and Reactive Oxygen Species Burst via Toll-Like Receptor 2, Toll-Like Receptor 4, and c-Jun N-Terminal Kinase Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Kai Zhang ◽  
Ning Jiang ◽  
Xiaoyu Sang ◽  
Ying Feng ◽  
Ran Chen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Trypanosoma Brucei ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Neutrophil Extracellular Traps ◽  
Oxygen Species ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Extracellular Traps ◽  
Toll Like Receptor 2

Trypanosoma brucei brucei is the causative agent of African animal trypanosomosis, which mainly parasitizes the blood of the host. Lipophosphoglycan (LPG), a polymer anchored to the surface of the parasites, activates the host immune response. In this study, we revealed that T. brucei LPG stimulated neutrophils to form neutrophil extracellular traps (NETs) and release the reactive oxygen species (ROS). We further analyzed the involvement of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) and explored the activation of signaling pathway enzymes in response to LPG stimulation. During the stimulation of neutrophils by LPG, the blockade using anti-TLR2 and anti-TLR4 antibodies reduced the phosphorylation of c-Jun N-terminal kinase (JNK), the release of DNA from the NETs, and the burst of ROS. Moreover, the addition of JNK inhibitor and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor exhibited similar effects. Our data suggest that T. brucei LPG activates the phosphorylation of JNK through TLR2 and TLR4 recognition, which causes the formation of NETs and the burst of ROS.

Sulfur dioxide-induced exacerbation of airway inflammation via reactive oxygen species production and the toll-like receptor 4/nuclear factor-κB pathway in asthmatic mice

2021 ◽  
Vol 37 (9) ◽  
pp. 564-572
Author(s):  
Lingxiu Zhang ◽  
Huilan Yi ◽  
Nan Sang
Keyword(s):  
Reactive Oxygen Species ◽  
Sulfur Dioxide ◽  
Airway Inflammation ◽  
Reactive Oxygen ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Asthmatic Airway

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.

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

2002 ◽  
Vol 169 (4) ◽  
pp. 2069-2075 ◽  
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

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

2014 ◽  
Vol 121 (6) ◽  
pp. 1270-1280 ◽  
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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