scholarly journals Phosphatidylinositol 4-Phosphate 5-Kinase α Facilitates Toll-like Receptor 4-mediated Microglial Inflammation through Regulation of the Toll/Interleukin-1 Receptor Domain-containing Adaptor Protein (TIRAP) Location

2013 ◽  
Vol 288 (8) ◽  
pp. 5645-5659 ◽  
Author(s):  
Tu Thi Ngoc Nguyen ◽  
Yong Min Kim ◽  
T. Doohun Kim ◽  
Oanh Thi Tu Le ◽  
Jae Jin Kim ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Adaptor Protein ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Phosphatidylinositol 4 ◽  
Receptor Domain ◽  
Microglial Inflammation

Oxymatrine inhibits lipopolysaccharide-induced inflammation by down-regulating Toll-like receptor 4/nuclear factor-kappa B in macrophages

2015 ◽  
Vol 93 (4) ◽  
pp. 253-260 ◽  
Author(s):  
Yu Zhang ◽  
Ruhong Yan ◽  
Yae Hu
Keyword(s):  
Nitric Oxide ◽  
Interleukin 1 ◽  
Chinese Herb ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Anti Inflammatory

Oxymatrine (OMT) is the quinolizidine alkaloid extracted from the Chinese herb Sophora flavescens Ait. that has many pharmacological effects and is used for the treatment of some inflammatory diseases. In this study, RAW264.7 cells and THP-1 differentiated macrophages were pretreated with various concentrations of OMT at 2 h prior to treatment with lipopolysaccharide (LPS) (1.0 μg/mL) for different durations. We detected the anti-inflammatory effect of OMT in LPS-stimulated macrophages and investigated the molecular mechanism. We showed that OMT pretreatment significantly inhibited the LPS-induced secretion of nitric oxide (NO), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) in supernatant, attenuated the mRNA levels of inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, and Toll-like receptor 4 (TLR4), increased TLR4 and phosphorylation of inhibitor of kappa B-alpha (p-IBα) in cytosol, and decreased the nuclear level of nuclear factor-κB (NF-κB) p65 in macrophages. In conclusion, OMT exerts anti-inflammatory properties in LPS-stimulated macrophages by down-regulating the TLR4/NF-κB pathway.

scholarly journals Scutellarin Attenuates Hypertension-Induced Expression of Brain Toll-Like Receptor 4/Nuclear Factor Kappa B

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Xingyong Chen ◽  
Xiaogeng Shi ◽  
Xu Zhang ◽  
Huixin Lei ◽  
Simei Long ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Nuclear Factor Kappa B ◽  
Interleukin 1 ◽  
Low Grade ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Hypertensive Rats ◽  
Toll Like Receptor 4 ◽  
Nuclear Factor Kappa ◽  
Proinflammatory Mediators

Hypertension is associated with low-grade inflammation, and Toll-like receptor 4 (TLR4) has been shown to be linked to the development and maintenance of hypertension. This study aimed to investigate the effects of scutellarin (administered by oral gavage daily for 2 weeks) on brain TLR4/nuclear factor kappa B-(NF-κB-) mediated inflammation and blood pressure in renovascular hypertensive (using the 2-kidney, 2-clip method) rats. Immunofluorescence and western immunoblot analyses revealed that hypertension contributed to the activation of TLR4 and NF-κB, accompanied by significantly enhanced expression of proinflammatory mediators, such as tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-18 (IL-18). Furthermore, expression of the antiapoptotic protein, myeloid cell leukemia-1 (Mcl1), was decreased, and the pro-apoptotic proteins, Bax and cleavedcaspase-3 p17 were increased in combined cerebral cortical/striatal soluble lysates. Scutellarin significantly lowered blood pressure and attenuated the number of activated microglia and macrophages in brains of hypertensive rats. Furthermore, scutellarin significantly reduced the expression of TLR4, NF-κB p65, TNF-α, IL-1β, IL-18, Bax and cleaved-caspase-3 p17, and increased the expression of Mcl1. Overall, these results revealed that scutellarin exhibits anti-inflammatory and anti-apoptotic properties and decreases blood pressure in hypertensive rats. Therefore, scutellarin may be a potential therapeutic agent in hypertension-associated diseases.

scholarly journals Central Role of Toll-Like Receptor 4 Signaling and Host Defense in Experimental Pneumonia Caused by Gram-Negative Bacteria

2005 ◽  
Vol 73 (1) ◽  
pp. 532-545 ◽  
Author(s):  
Jill R. Schurr ◽  
Erana Young ◽  
Pat Byrne ◽  
Chad Steele ◽  
Judd E. Shellito ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adaptor Protein ◽  
Mouse Strains ◽  
Gram Negative Bacteria ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tlr4 Signaling ◽  
Gram Negative ◽  
Experimental Pneumonia

ABSTRACT Toll-like receptor 4 (TLR4) has been identified as a receptor for lipopolysaccharide. However, the precise role of TLR4 in regulating gene expression in response to an infection caused by gram-negative bacteria has not been fully elucidated. The role of TLR4 signaling in coordinating gene expression was assessed by gene expression profiling in lung tissue in a mouse model of experimental pneumonia with a low-dose infection of Klebsiella pneumoniae. We analyzed four mouse strains: C57BL/6 mice, which are resistant to bacterial dissemination; 129/SvJ mice, which are susceptible; C3H/HeJ mice, which are susceptible and have defective TLR4 signaling; and their respective control strain, C3H/HeN (intermediate resistance). At 4 h after infection, C57BL/6 and C3H/HeN mice demonstrated the greatest number of genes, with 67 shared induced genes which were TLR4 dependent and highly associated with the resistance phenotype. These genes included cytokine and chemokine genes required for neutrophil activation or recruitment, growth factor receptors, MyD88 (a critical adaptor protein for TLR signaling), and adhesion molecules. TLR4 signaling accounted for over 74% of the gene expression in the C3H background. These data suggest that early TLR4 signaling controls the vast majority of gene expression in the lung in response to an infection caused by gram-negative bacteria and that this subsequent gene expression determines survival of the host.

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