scholarly journals The protective effect of the anti-Toll-like receptor 9 antibody against acute cytokine storm caused by immunostimulatory DNA

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Yusuke Murakami ◽  
Ryutaro Fukui ◽  
Yuji Motoi ◽  
Takuma Shibata ◽  
Shin-Ichiroh Saitoh ◽  
...  
Keyword(s):  
Protective Effect ◽  
Cytokine Storm ◽  
Toll Like Receptor ◽  
Immunostimulatory Dna

Protective Effect of Ginsenoside Rb1 Nanoparticles Against Contrast-Induced Nephropathy by Inhibiting High Mobility Group Box 1 Gene/Toll-Like Receptor 4/NF-κB Signaling Pathway

2021 ◽  
Vol 17 (10) ◽  
pp. 2085-2098
Author(s):  
Shuai Zhou ◽  
Shan Lu ◽  
Sen Guo ◽  
Luosha Zhao ◽  
Zhanying Han ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Protective Effect ◽  
High Mobility ◽  
High Mobility Group ◽  
Ginsenoside Rb1 ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Contrast Induced Nephropathy

With the progress made in the widespread application of interventional radiology procedures, there has been an increasing number of patients who suffer from cardiovascular diseases and go through imaging and interventional treatment with iodine contrast medium (ICM) year by year. In turn, there has been an increasing amount of concern over acute kidney injury (AKI) brought about by ICM. As evidenced by numerous studies, the initiation of inflammatory response plays a critical role in the development of ICM-induced AKI. Correspondingly, the strategy of targeting renal inflammatory response and cytokine release could provide an effective solution to mitigating the ICM-induced AKI. Moreover, Ginsenoside Rb1 (GRb1) constitutes one of the major active components of ginseng and features a wide range of vital biological functions. Judging from the research findings, GRb1 could impose antioxidant and anti-inflammatory effects on cardiovascular diseases, in addition to lung, liver and kidney diseases. However, reports on whether GRb1 could impose a protective effect against contrast-induced nephropathy (CIN) are absent. In this study, we have examined the therapeutic effects imposed by GRb1 as well as the potential molecular mechanism by establishing an in vivo and in vitro model of CIN. In addition, we have set up a mouse model of CIN through sequential intravenous injection of indomethacin, N(ω)-nitro-Larginine methyl ester (L-NAME), and iopromide. To further enhance the bioavailability of GRb1, we have encapsulated GRb1 with polyethylene glycol (PEG)/poly lactic-co-glycolic acid (PLGA) nanocarriers to generate GRb1 nanoparticles (NPs) conducting the in vivo experiments. During the in vitro experiments, we have adopted GRb1 to treat NRK-52E cells or cells transfected with the high mobility group box 1 gene (HMGB1) overexpression plasmid. As shown by the in vivo experimental results, GRb1 NPs could evidently improve the renal dysfunction in CIN, diminish the extent of apoptosis of tubular epithelial cells, and reduce the expression of high mobility group box 1 (HMGB1) and cytokines (tumor necrosis factor (TNF-α), interleukin (IL) 6 and IL-1β). In addition, GRb1 NPs are found to be capable of preventing the activation of Toll-like receptor 4 (TLR4)/NF-κB signaling pathway triggered by contrast medium. The in vitro experimental results have exactly confirmed the findings of the in vivo experiments. In the meantime, through the observation of the in vitro assays, overexpression of HMGB1 can partially counteract the beneficial effects imposed by GRb1. Judging from our research data, GRb1 could impose a protective effect against CIN by inhibiting inflammatory response via HMGB1/TLR4/NF-κB pathway, whereas HMGB1 constitutes a critical molecular target of GRb1.

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 Toll-like Receptor 4 Signaling Pathway in the Protective Effect of Pioglitazone on Experimental Immunoglobulin A Nephropathy

2017 ◽  
Vol 130 (8) ◽  
pp. 906-913 ◽  
Author(s):  
Jia-Nan Zou ◽  
Jing Xiao ◽  
Sha-Sha Hu ◽  
Chen-Sheng Fu ◽  
Xiao-Li Zhang ◽  
...  
Keyword(s):  
Protective Effect ◽  
Signaling Pathway ◽  
Immunoglobulin A ◽  
Toll Like Receptor ◽  
Immunoglobulin A Nephropathy ◽  
Toll Like Receptor 4
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