scholarly journals Identification of Interaction Sites for Dimerization and Adapter Recruitment in Toll/Interleukin-1 Receptor (TIR) Domain of Toll-like Receptor 4

2011 ◽  
Vol 287 (6) ◽  
pp. 4088-4098 ◽  
Author(s):  
Celia Bovijn ◽  
Peter Ulrichts ◽  
Anne-Sophie De Smet ◽  
Dominiek Catteeuw ◽  
Rudi Beyaert ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tir Domain ◽  
Interaction Sites

scholarly journals Common Interaction Surfaces of the Toll-Like Receptor 4 Cytoplasmic Domain Stimulate Multiple Nuclear Targets

2003 ◽  
Vol 23 (7) ◽  
pp. 2543-2555 ◽  
Author(s):  
Tapani Ronni ◽  
Vishal Agarwal ◽  
Michael Haykinson ◽  
Margaret E. Haberland ◽  
Genhong Cheng ◽  
...  
Keyword(s):  
Target Genes ◽  
Interleukin 1 ◽  
Adaptor Proteins ◽  
Critical Surface ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tlr4 Signaling ◽  
Tir Domain ◽  
Anti Inflammatory ◽  
Mutant Phenotypes

ABSTRACT Toll-like receptor 4 (TLR4) mediates the host response to lipopolysaccharide (LPS) by promoting the activation of pro- and anti-inflammatory cytokine genes. To activate each gene, numerous signal transduction pathways are required. The adaptor proteins MyD88 and TIRAP contribute to the activation of several and possibly all pathways via direct interactions with TLR4's Toll/interleukin-1 receptor (IL-1R) (TIR) domain. However, additional adaptors that are required for the activation of specific subsets of pathways may exist, which could contribute to the differential regulation of target genes. Furthermore, it remains unknown whether direct interactions that have been reported between TIR domains and other proteins are required for TLR4 signaling. To address these issues, we systematically mutated the TLR4 TIR domain in the context of a CD4/TLR4 fusion protein. Several exposed residues defining at least two structural surfaces were required in macrophages for activation of the proinflammatory IL-12 p40 and anti-inflammatory IL-10 promoters, as well as promoters dependent on individual transcription factors. Interestingly, the same residues were required by all promoters tested, suggesting that the signaling pathways diverge downstream of the adaptors. The mutant phenotypes provide a framework for future studies of TLR4 signaling, as the interaction supported by each critical surface residue will need to be defined.

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 Targeting Toll-like Receptor (TLR) Signaling by Toll/Interleukin-1 Receptor (TIR) Domain-containing Adapter Protein/MyD88 Adapter-like (TIRAP/Mal)-derived Decoy Peptides

2012 ◽  
Vol 287 (29) ◽  
pp. 24641-24648 ◽  
Author(s):  
Leah A. Couture ◽  
Wenji Piao ◽  
Lisa W. Ru ◽  
Stefanie N. Vogel ◽  
Vladimir Y. Toshchakov
Keyword(s):  
Interleukin 1 ◽  
Adapter Protein ◽  
Toll Like Receptor ◽  
Tlr Signaling ◽  
Tir Domain

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 Interaction between interleukin-1 receptor 2 and Toll-like receptor 4, and cervical cytokines

2011 ◽  
Vol 90 (2) ◽  
pp. 220-226 ◽  
Author(s):  
Kelli K. Ryckman ◽  
Scott M. Williams ◽  
Marijane A. Krohn ◽  
Hyagriv N. Simhan
Keyword(s):  
Interleukin 1 ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4
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