scholarly journals Pre-Treatment with Ten-Minute Carbon Dioxide Inhalation Prevents Lipopolysaccharide-Induced Lung Injury in Mice via Down-Regulation of Toll-Like Receptor 4 Expression

2019 ◽  
Vol 20 (24) ◽  
pp. 6293 ◽  
Author(s):  
Shih-En Tang ◽  
Shu-Yu Wu ◽  
Shi-Jye Chu ◽  
Yuan-Sheng Tzeng ◽  
Chung-Kan Peng ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Lung Injury ◽  
Protective Effect ◽  
Surface Expression ◽  
Protein Carbonyls ◽  
Lung Injury Score ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Down Regulation ◽  
Pre Treatment

Various animal studies have shown beneficial effects of hypercapnia in lung injury. However, in patients with acute respiratory distress syndrome (ARDS), there is controversial information regarding the effect of hypercapnia on outcomes. The duration of carbon dioxide inhalation may be the key to the protective effect of hypercapnia. We investigated the effect of pre-treatment with inhaled carbon dioxide on lipopolysaccharide (LPS)-induced lung injury in mice. C57BL/6 mice were randomly divided into a control group or an LPS group. Each LPS group received intratracheal LPS (2 mg/kg); the LPS groups were exposed to hypercapnia (5% carbon dioxide) for 10 min or 60 min before LPS. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected to evaluate the degree of lung injury. LPS significantly increased the ratio of lung weight to body weight; concentrations of BALF protein, tumor necrosis factor-α, and CXCL2; protein carbonyls; neutrophil infiltration; and lung injury score. LPS induced the degradation of the inhibitor of nuclear factor-κB-α (IκB-α) and nuclear translocation of NF-κB. LPS increased the surface protein expression of toll-like receptor 4 (TLR4). Pre-treatment with inhaled carbon dioxide for 10 min, but not for 60 min, inhibited LPS-induced pulmonary edema, inflammation, oxidative stress, lung injury, and TLR4 surface expression, and, accordingly, reduced NF-κB signaling. In summary, our data demonstrated that pre-treatment with 10-min carbon dioxide inhalation can ameliorate LPS-induced lung injury. The protective effect may be associated with down-regulation of the surface expression of TLR4 in the lungs.

scholarly journals Dexmedetomidine reduces ventilator-induced lung injury (VILI) by inhibiting Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway

2018 ◽  
Vol 18 (2) ◽  
pp. 162-169 ◽  
Author(s):  
Hongli Chen ◽  
Xiaotong Sun ◽  
Xiaomei Yang ◽  
Yonghao Hou ◽  
Xiaoqian Yu ◽  
...  
Keyword(s):  
Lung Injury ◽  
Protective Effect ◽  
Tidal Volume ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Nuclear Factor ◽  
Pathological Changes ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Ventilator Induced Lung Injury

Mechanical ventilation (MV) may lead to ventilator-induced lung injury (VILI). Previous research has shown that dexmedetomidine attenuates pulmonary inflammation caused by MV, but the underlying mechanisms remain unclear. Our study aims to test whether dexmedetomidine has a protective effect against VILI and to explore the possible molecular mechanisms using the rat model. Thirty adult male Wistar rats weighing 200-250 g were randomly assigned to 5 groups (n = 6): control, low tidal volume MV (LMV), high tidal volume (HVT) MV (HMV), HVT MV + dexmedetomidine (DEX), HVT MV + dexmedetomidine + yohimbine (DEX+Y). Rats were euthanized after being ventilated for 4 hours. Pathological changes, lung wet/dry (W/D) weight ratio, lung myeloperoxidase (MPO) activity, levels of inflammatory cytokines (i.e., interleukin [IL]-1β, tumor necrosis factor alpha [TNF-α], and IL-6) in the bronchoalveolar lavage fluid (BALF) and lung tissues, expression of Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB, and activation of NF-κB in lung tissues were measured. Compared with HMV, DEX group showed fewer pathological changes, lower W/D ratios and decreased MPO activity of the lung tissues and lower concentrations of the inflammatory cytokines in the BALF and lung tissues. Dexmedetomidine significantly inhibited the expression of TLR4 and NF-κB and activation of NF-κB. Yohimbine partly alleviated the effects of dexmedetomidine. Dexmedetomidine reduced the inflammatory response to HVT-MV and had a protective effect against VILI, with the inhibition of the TLR4/NF-κB signaling pathway, at least partly via α2-adrenoceptors.

Chelidonine Attenuates Sepsis-Induced Acute Lung Injury via Suppressing Toll-like Receptor 4/Myeloid Differentiation Factor 88/Nuclear Factor-॔B Signaling Pathway in Newborn Mice

2020 ◽  
Vol 19 (1) ◽  
pp. 120-126
Author(s):  
Ayinuerguli Adili ◽  
Adilijiang Kari ◽  
Chuanlong Song ◽  
Abulaiti Abuduhaer
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Factor Kappa B ◽  
Myeloid Differentiation ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Inflammatory Infiltration ◽  
Newborn Mice ◽  
Myeloid Differentiation Factor

We have examined the mechanism underlying amelioration of sepsis-induced acute lung injury by chelidonine in newborn mice. To this end, a sepsis model was established using cecal ligation and puncture in newborn mice. The sepsis-induced acute lung injury was associated with an increased inflammatory infiltration and pulmonary congestion, as well as abnormal alveolar morphology. The lung injury-associated increased tumor necrosis factor-α and interleukin-1β in bronchoalveolar lavage fluid and lung, the markers of inflammatory infiltration and pulmonary congestion, diminished by chelidonine treatment. Chelidonine administration also downregulated protein levels of toll-like receptor 4, myeloid differentiation factor 88, phosphorylated nuclear factor-kappa B, and nuclear factor-kappa B that are elevated in response to sepsis. In conclusion, chelidonine provides a potential therapeutic strategy for newborn mice with acute lung injury.

Juglone Attenuates Sepsis-Induced Acute Lung Injury via Suppression of the TLR4/Nf-κb Pathway

2020 ◽  
Vol 18 (2) ◽  
pp. 201-206
Author(s):  
Qiu Nan ◽  
Xu Xinmei ◽  
He Yingying ◽  
Fan Chengfen
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Factor Kappa B ◽  
Cecal Ligation ◽  
Myeloperoxidase Activity ◽  
Nuclear Factor ◽  
Cecal Ligation And Puncture ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Nuclear Factor Kappa

Sepsis, with high mortality, induces deleterious organ dysfunction and acute lung injury. Natural compounds show protective effect against sepsis-induced acute lung injury. Juglone, a natural naphthoquinone, demonstrates pharmacological actions as a pro-apoptotic substrate in tumor treatment and anti-inflammation substrate in organ injury. In this study, the influence of juglone on sepsis-induced acute lung injury was investigated. First, a septic mice model was established via cecal ligation and puncture, and then verified via histopathological analysis of lung tissues, the wet/dry mass ratio and myeloperoxidase activity was determined. Cecal ligation and puncture could induce acute lung injury in septic mice, as demonstrated by alveolar damage and increase of wet/dry mass ratio and myeloperoxidase activity. However, intragastric administration juglone attenuated cecal ligation and puncture-induced acute lung injury. Secondly, cecal ligation and puncture-induced increase of inflammatory cells in bronchoalveolar lavage fluid was also alleviated by the administration of juglone. Similarly, the protective effect of juglone against cecal ligation and puncture-induced acute lung injury was accompanied by a reduction of pro-inflammatory factor secretion in bronchoalveolar lavage fluid and lung tissues. Cecal ligation and puncture could activate toll-like receptor 4/nuclear factor-kappa B signaling pathway, and administration of juglone suppressed toll-like receptor 4/nuclear factor-kappa B activation. In conclusion, juglone attenuated cecal ligation and puncture-induced lung damage and inflammatory response through inactivation of toll-like receptor 4/nuclear factor-kappa B, suggesting a potential therapeutic strategy in the treatment of sepsis-induced acute lung injury.

scholarly journals Salidroside Protects Against Influenza A Virus-Induced Acute Lung Injury in Mice

Dose-Response ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 155932582110113
Author(s):  
Rufeng Lu ◽  
Yueguo Wu ◽  
Honggang Guo ◽  
Zhuoyi Zhang ◽  
Yuzhou He
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Influenza A Virus ◽  
Influenza A ◽  
H1n1 Virus ◽  
Antiviral Agents ◽  
Toll Like Receptor ◽  
Virus Infections ◽  
Toll Like Receptor 4 ◽  
Inflammatory Cytokine Production

Influenza A virus infections can cause acute lung injury (ALI) in humans; thus, the identification of potent antiviral agents is urgently required. Herein, the effects of salidroside on influenza A virus-induced ALI were investigated in a murine model. BALB/c mice were intranasally inoculated with H1N1 virus and treated with salidroside. The results of this study show that salidroside treatment (30 and 60 mg/kg) significantly attenuated the H1N1 virus-induced histological alterations in the lung and inhibited inflammatory cytokine production. Salidroside also decreased the wet/dry ratio, viral titers, and Toll-like receptor 4 expression in the lungs. Therefore, salidroside may represent a potential therapeutic reagent for the treatment of influenza A virus-induced ALI.

Bilobalide Ameliorates Sepsis Induced Acute Lung Injury by Inactivating Toll-Like Receptor 4/Myeloid Differentiation Factor 88/Nuclear Factor-Kappa B Pathway

2020 ◽  
Vol 19 (3) ◽  
pp. 277-282
Author(s):  
Tian Liu ◽  
Siyi Jiang ◽  
Shengwei Jia ◽  
Fuxiang Fan
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Factor Kappa B ◽  
Cecal Ligation ◽  
Myeloid Differentiation ◽  
Nuclear Factor ◽  
Cecal Ligation And Puncture ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Myeloid Differentiation Factor

Acute lung injury refers to the injury of alveolar epithelial cells and pulmonary capillary endothelial cells caused by noncardiac factors. To better combat the disease, there is an urgent need to develop more effective drugs. Sepsis is a syndrome of systemic inflammation caused by infection, and the molecular mechanism by which sepsis induces acute lung injury has not been clearly determined. Bilobalide is a unique component of Ginkgo biloba. Although it has multiple biological functions, its role in sepsis induced acute lung injury needs further study. In this study, we found that bilobalide alleviated cecal ligation and puncture induced acute lung injury. Additionally, bilobalide regulated cecal ligation and puncture induced lung injury through toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B pathway. We therefore conclude that bilobalide may be a potential drug for the treatment of sepsis induced acute lung injury.

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