scholarly journals Tripterygium Glycosides Tablet Ameliorates Renal Tubulointerstitial Fibrosis via the Toll-Like Receptor 4/Nuclear Factor Kappa B Signaling Pathway in High-Fat Diet Fed and Streptozotocin-Induced Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Ze-jun Ma ◽  
Xiao-na Zhang ◽  
Li Li ◽  
Wei Yang ◽  
Shan-shan Wang ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Nuclear Factor Kappa B ◽  
Diabetic Rats ◽  
Tubulointerstitial Fibrosis ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
High Fat ◽  
Toll Like Receptor 4 ◽  
Renal Tubulointerstitial Fibrosis ◽  
Tripterygium Glycosides

Tripterygium glycosides tablet (TGT) is a Chinese traditional medicine that has been shown to protect podocytes from injury and reduce the proteinuria. The aim of this study was to assess the effect of TGT on renal tubulointerstitial fibrosis and its potential mechanism in high-fat diet fed and STZ-induced diabetic rats. Rats were randomly divided into normal control rats (NC group), diabetic rats without drug treatment (DM group), and diabetic rats treated with TGT (1, 3, or 6 mg/kg/day, respectively) for 8 weeks. The results showed that 24 h proteinuria and urinary N-acetyl-glucosaminidase (NAG) in diabetic rats were decreased by TGT treatment without affecting blood glucose. Masson’s trichrome stains showed that apparent renal tubulointerstitial fibrosis was found in DM group, which was ameliorated by TGT treatment. The expression ofα-SMA was significantly decreased, accompanied by increased expression of E-cadherin in TGT-treated rats, but not in untreated DM rats. Further studies showed that TGT administration markedly reduced expression of TLR4, NF-κB, IL-1β, and MCP-1 in TGT-treated diabetic rats. These results showed that TGT could ameliorate renal tubulointerstitial fibrosis, the mechanism which may be at least partly associated with the amelioration of EMT through suppression of the TLR4/NF-κB pathway.

scholarly journals Palmitic acid induces guanylin gene expression through the Toll-like receptor 4/nuclear factor-κB pathway in rat macrophages

2019 ◽  
Vol 317 (6) ◽  
pp. C1239-C1246
Author(s):  
Sayaka Akieda-Asai ◽  
Hao Ma ◽  
Yukari Date
Keyword(s):  
Gene Expression ◽  
Palmitic Acid ◽  
Gene Transcription ◽  
Proinflammatory Cytokines ◽  
High Fat Diet ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
High Fat ◽  
Toll Like Receptor 4

Recently, we showed that double-transgenic rats overexpressing guanylin (Gn), a bioactive peptide, and its receptor, guanylyl cyclase-C (GC-C), specifically in macrophages demonstrate an antiobesity phenotype and low-expression levels of proinflammatory cytokines in the mesenteric fat even when fed a high-fat diet. Here, we examined the levels and mechanism of Gn and GC-C transcription following saturated fatty acid and lipopolysaccharide (LPS), an activator of Toll-like receptor 4 (TLR4), exposure by using the NR8383 macrophage cell line. In addition, the levels of guanylin and cGMP were increased by addition of either palmitic acid or LPS. Next, we investigated the interaction of the gene transcription and nuclear factor-κB (NF-κB) by using an NF-κB inhibitor and chromatin immunoprecipitation assay. We showed that palmitic acid induced Gn gene expression via TLR4 and NF-κB. Moreover, we demonstrated that NF-κB binding to the Gn promoter was responsible for the induction of gene transcription by palmitic acid or LPS. Our results indicate that saturated fatty acids such as palmitic acid activate Gn gene expression via the NF-κB pathway, raising the possibility that the activated Gn-GC-C system may contribute to the inhibition of high-fat diet-induced proinflammatory cytokines in macrophages.

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.

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.

scholarly journals Apolipoprotein E deficiency and high-fat diet cooperate to trigger lipidosis and inflammation in the lung via the toll-like receptor 4 pathway

2015 ◽  
Vol 12 (2) ◽  
pp. 2589-2597 ◽  
Author(s):  
QIUFANG OUYANG ◽  
ZIYANG HUANG ◽  
HUILI LIN ◽  
JINGQIN NI ◽  
HUIXIA LU ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
High Fat Diet ◽  
Toll Like Receptor ◽  
High Fat ◽  
Toll Like Receptor 4

scholarly journals Selective overexpression of Toll-like receptor-4 in skeletal muscle impairs metabolic adaptation to high-fat feeding

2015 ◽  
Vol 309 (3) ◽  
pp. R304-R313 ◽  
Author(s):  
Ryan P. McMillan ◽  
Yaru Wu ◽  
Kevin Voelker ◽  
Gabrielle Fundaro ◽  
John Kavanaugh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
High Fat Diet ◽  
Whole Body ◽  
Metabolic Adaptation ◽  
Acid Oxidation ◽  
Chow Diet ◽  
Toll Like Receptor ◽  
High Fat ◽  
Toll Like Receptor 4 ◽  
Fat Feeding

Toll-like receptor-4 (TLR-4) is elevated in skeletal muscle of obese humans, and data from our laboratory have shown that activation of TLR-4 in skeletal muscle via LPS results in decreased fatty acid oxidation (FAO). The purpose of this study was to determine whether overexpression of TLR-4 in skeletal muscle alters mitochondrial function and whole body metabolism in the context of a chow and high-fat diet. C57BL/6J mice (males, 6–8 mo of age) with skeletal muscle-specific overexpression of the TLR-4 (mTLR-4) gene were created and used for this study. Isolated mitochondria and whole muscle homogenates from rodent skeletal muscle (gastrocnemius and quadriceps) were investigated. TLR-4 overexpression resulted in a significant reduction in FAO in muscle homogenates; however, mitochondrial respiration and reactive oxygen species (ROS) production did not appear to be affected on a standard chow diet. To determine the role of TLR-4 overexpression in skeletal muscle in response to high-fat feeding, mTLR-4 mice and WT control mice were fed low- and high-fat diets for 16 wk. The high-fat diet significantly decreased FAO in mTLR-4 mice, which was observed in concert with elevated body weight and fat, greater glucose intolerance, and increase in production of ROS and cellular oxidative damage compared with WT littermates. These findings suggest that TLR-4 plays an important role in the metabolic response in skeletal muscle to high-fat feeding.

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