scholarly journals Alkannin Inhibited Hepatic Inflammation in Diabetic Db/Db Mice

2018 ◽  
Vol 45 (6) ◽  
pp. 2461-2470 ◽  
Author(s):  
Wenhua Xue ◽  
Zhirui Fan ◽  
Yuanzhe Li ◽  
Lifeng Li ◽  
Tengfei Zhang ◽  
...  
Keyword(s):  
Western Blotting ◽  
Tumour Necrosis ◽  
Rho Kinase ◽  
Hepatic Inflammation ◽  
Tnf Α ◽  
Hepatoprotective Effects ◽  
Kinase Pathway ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Background/Aims: The current study was designed to investigate the protective role of alkannin (ALK) on liver injury in diabetic C57BL/KsJ-db/db mice and explore its potential mechanisms. Methods: An oral glucose tolerance test (OGTT) was performed. The levels of insulin, alanine aminotransferase (ALT), aspartate aminotransaminase (AST), total cholesterol (TC) and triglyceride (TG) were determined by commercial kits. The pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α were determined by ELISA. The levels of the ROCK/NF-κB pathway were determined by Western blotting. Results: The contents of pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α were inhibited by ALK, metformin or fasudil in diabetic db/db mice. Further, Western blotting analysis showed that the expression of Rho, ROCK1, ROCK2, p-NF-κBp65, and p-IκBα was significantly reversed by ALK treatment. In human hepatic HepG2 cells, the hepatoprotective effects of ALK were further characterized. With response to palmitic acid-challenge, increased amounts of insulin, ALT, AST, TG, and TC were observed, whereas ALK pretreatment significantly inhibited their leakage in HepG2 cells without appreciable cytotoxic effects. The inflammation condition was recovered with ALK treatment as shown by changes of IL-1β, IL-6 and TNF-α. Further, Western blotting analysis also suggested that ALK improves hepatic inflammation in a Rho-kinase pathway. Conclusion: The present study successfully investigated the role of Rho-kinase signalling in diabetic liver injury. ALK exhibited hepatoprotective effects in diabetic db/db mice, and it might act through improving hepatic inflammation through the Rho-kinase pathway.

Role of Exercise Activity in Alleviating Neuropathic Pain in Diabetes via Inhibition of the Pro-Inflammatory Signal Pathway

2018 ◽  
Vol 21 (1) ◽  
pp. 14-21 ◽  
Author(s):  
Xiao-Qiu Ma ◽  
Jing Qin ◽  
Hong-Yan Li ◽  
Xiu-Li Yan ◽  
Yong Zhao ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Tumor Necrosis ◽  
Signal Pathway ◽  
Sensory Nerves ◽  
Glucose Levels ◽  
Tnf Α ◽  
Exercise Activity ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Hyperalgesia and allodynia are commonly observed in patients with diabetic neuropathy. The treatment and management of painful peripheral neuropathy is important in these patients. The purpose of this study was to examine the role of exercise in modulating neuropathic pain induced by diabetes. Diabetes was induced in rats by an intraperitoneal injection of streptozotocin (STZ). Control rats received saline injections. Groups included control rats without exercise (NT-control, n = 12), control rats with exercise (EX-control, n = 16), STZ rats without exercise (NT-STZ, n = 18), and STZ rats with exercise (EX-STZ, n = 22). Rats in EX groups ran on a treadmill 4 days/week for 5 weeks beginning from the week of STZ administration. Mechanical hypersensitivity (mechanical paw withdrawal thresholds [PWTs]) and glucose levels were tested weekly. Then, enzyme-linked immunoassay and Western blot analysis were used to determine the levels of pro-inflammatory cytokines (PICs) and their receptors in sensory nerves. PWTs were significantly increased after 4–5 weeks of exercise in STZ rats ( p < .05 vs. NT-STZ rats). Inhibition of neuropathic pain by exercise in STZ rats was accompanied by decreases in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels and downregulated expression of their receptors. Furthermore, blocking individual PIC receptors elevated PWTs to a greater degree in STZ rats ( p < .05 vs. control rats). Overall, our data suggest that exercise can play a role in improving neuropathic pain induced by STZ and that PIC signaling is a part of the mechanism involved in this effect.

The role of tumour necrosis factor (TNF-α) in experimental autoimmune uveoretinitis (EAU)

2004 ◽  
Vol 23 (6) ◽  
pp. 617-637 ◽  
Author(s):  
Andrew D. Dick ◽  
John V. Forrester ◽  
Janet Liversidge ◽  
Andrew P. Cope
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Experimental Autoimmune Uveoretinitis ◽  
Tnf Α ◽  
Necrosis Factor ◽  
Experimental Autoimmune

scholarly journals The tumour necrosis factor-sensitive pool of sphingomyelin is resynthesized in a distinct compartment of the plasma membrane

1998 ◽  
Vol 333 (1) ◽  
pp. 91-97 ◽  
Author(s):  
Nathalie ANDRIEU-ABADIE ◽  
Stéphane CARPENTIER ◽  
Robert SALVAYRE ◽  
Thierry LEVADE
Keyword(s):  
Plasma Membrane ◽  
Golgi Apparatus ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Signal Transduction Pathway ◽  
Recycling Endosomes ◽  
Vesicular Traffic ◽  
Tnf Α ◽  
Necrosis Factor

Sphingomyelin (SM) biosynthesis is believed to occur in the early Golgi apparatus, plasma membrane and recycling endosomes. In the present study, the localization of the SM synthesis that follows its hydrolysis upon activation of the SM signal-transduction pathway was investigated in human skin fibroblasts treated with tumour necrosis factor (TNF) α. After TNFα-induced degradation, the intracellular SM levels returned to baseline levels within 30–60 min in cells treated at 37 °C. Pretreatment or co-incubation of cells with bacterial sphingomyelinase or phospholipase C, decreasing the SM and phosphatidylcholine content in the external leaflet of the plasma membrane respectively, did not inhibit SM resynthesis. However, SM resynthesis was not observed when TNFα-treated cells were continuously exposed to exogenous sphingomyelinase, suggesting that under these particular conditions the resynthesized SM becomes accessible to the enzyme. Furthermore, whereas inhibition of vesicular traffic/endocytosis at 4 °C blocked exoplasmic SM resynthesis, it did not alter SM resynthesis in TNFα-treated fibroblasts, negating the role of endosomes and the Golgi apparatus. This was further evidenced by the finding that after SM resynthesis, TNFα was again able to promote SM turnover, even at 4 °C. In addition, when the exoplasmic leaflet SM was hydrolysed by treating fibroblasts with bacterial sphingomyelinase, resynthesis of SM occurred at 37 °C much more slowly than after TNFα treatment. These findings support strongly the conclusion that the SM, which is resynthesized after TNFα-induced hydrolysis, resides in the cytosolic leaflet of the plasma membrane, and that the process involved in this resynthesis displays characteristics different from those of the previously described SM synthases.

Role of tumour necrosis factor receptor-1 and nuclear factor-κB in production of TNF-α-induced pro-inflammatory microparticles in endothelial cells

2014 ◽  
Vol 112 (09) ◽  
pp. 580-588 ◽  
Author(s):  
Sung Kyul Lee ◽  
Seung-Hee Yang ◽  
Il Kwon ◽  
Ok-Hee Lee ◽  
Ji Hoe Heo
Keyword(s):  
Endothelial Cells ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Nuclear Factor Κb ◽  
Tumour Necrosis Factor Receptor ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Tnf Α ◽  
Necrosis Factor

SummaryTumour necrosis factor-α (TNF-α) is upregulated in many inflammatory diseases and is also a potent agent for microparticle (MP) generation. Here, we describe an essential role of TNF-α in the production of endothelial cell-derived microparticles (EMPs) in vivo and the function of TNF-α-induced EMPs in endothelial cells. We found that TNF-α rapidly increased blood levels of EMPs in mice. Treatment of human umbilical vein endothelial cells (HUVECs) with TNF-α also induced EMP formation in a time-dependent manner. Silencing of TNF receptor (TNFR)-1 or inhibition of the nuclear factor-κB (NF-κB) in HUVECs impaired the production of TNF-α-induced EMP. Incubation of HUVECs with PKH-67-stained EMPs showed that endothelial cells readily engulfed EMPs, and the engulfed TNF-α-induced EMPs promoted the expression of pro-apoptotic molecules and upregulated intercellular adhesion molecule-1 level on the cell surface, which led to monocyte adhesion. Collectively, our findings indicate that the generation of TNF-α-induced EMPs was mediated by TNFR1 or NF-κB and that EMPs can contribute to apoptosis and inflammation of endothelial cells.

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