R753Q Polymorphism Inhibits Toll-like Receptor (TLR) 2 Tyrosine Phosphorylation, Dimerization with TLR6, and Recruitment of Myeloid Differentiation Primary Response Protein 88

Xiong, Yanbao; Song, Chang; Snyder, Greg; Sundberg, Eric J.; Medvedev, Andrei E.

doi:10.1074/jbc.m112.375493

Cited by 73 publications

(82 citation statements)

References 78 publications

(94 reference statements)

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“…Thus, this mutation renders TLR2 signaling incompetent by impairing its tyrosine phosphorylation, dimerization with TLR6, and recruitment of the myeloid differentiation primary response gene 88 (MyD88) and MyD88-adapter-like proteins (18). However, the correlation between gout and TLR2 gene polymorphisms remains unclear.…”

Section: Discussionmentioning

confidence: 98%

Association of Toll-like receptor 2 polymorphisms with gout

et al. 2014

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Abstract. Gout is the most common autoinflammatory arthritis characterized by elevated serum urate and recurrent attacks of intra-articular crystal deposition of monosodium urate (MSU) in tissues. The pathogenesis of gout has not been fully determined, although certain genetic factors are involved in the development of gout. Accumulated data suggested that MSU crystal-induced inflammation is a paradigm of innate immunity. As Toll-like receptors (TLRs) are the underlying mechanisms of the innate immune response, the present study aimed to investigate whether TLR2 polymorphisms are associated with gout. Two single-nucleotide polymorphisms (Arg677Trp and Arg753Gln, rs5743708) in TLR2 were genotyped by polymerase chain reaction-restriction fragment length polymorphism and the -196 to -174 del polymorphism was investigated using the allele-specific polymerase chain reaction in 431 individuals (215 patients with gout and 216 healthy controls). TLR2 Arg677Trp and Arg753Gln genotyping indicated that all the positive samples were of the wild-type genotype. No significant differences in genotype (χ 2 =1.686, P=0.430) and allele (χ 2 =1.430, P=0.232) frequencies of the -196 to -174 del polymorphism between the patients with gout and the control groups was observed. Our results suggested that the TLR2 Arg677Trp, Arg753Gln and the -196 to -174 del polymorphisms were not associated with susceptibility to primary gouty arthritis.

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Section: Discussionmentioning

confidence: 98%

Association of Toll-like receptor 2 polymorphisms with gout

et al. 2014

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“…The direct role of TLR2 activation in the regulation of autophagy is not well ascribed; however, several evidences have been suggesting that TLR2 activation is capable of inducing autophagy by a mechanism dependent on the activation of p38 MAPK (Seto et al, 2012). Interestingly, the R753Q TLR2 polymorphism was shown to render TLR2 incapable of inducing tyrosine phosphorylation and heterodimerization with TLR6 upon agonist binding, ultimately leading to impaired capacity of p38 and autophagy activation (Xiong et al, 2012).…”

Section: Figmentioning

confidence: 99%

Autophagy in the Fight Against Tuberculosis

Bento

Empadinhas

Mendes

2015

DNA and Cell Biology

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Tuberculosis (TB), a chronic infectious disease mainly caused by the tubercle bacillus Mycobacterium tuberculosis, is one of the world's deadliest diseases that has afflicted humanity since ancient times. Although the number of people falling ill with TB each year is declining, its incidence in many developing countries is still a major cause of concern. Upon invading host cells by phagocytosis, M. tuberculosis can replicate within infected cells by arresting the maturation of the phagosome whose function is to target the pathogen for elimination. Host cells have mechanisms of controlling this evasion by inducing autophagy, an elaborate cellular process that targets bacteria for progressive elimination, decreasing bacterial loads within infected cells. In addition, autophagy activation also aids in the control of inflammation, contributing to a more efficient innate immune response against M. tuberculosis. Several innovative TB therapies have been envisaged based on autophagy manipulation, with some of them revealing high potential for future clinical trials and eventual implementation in healthcare systems. Thus, this review highlights the recent advances on the innate immune response regulation by autophagy upon M. tuberculosis infection and the promising new autophagy-based therapies for TB. Mycobacterium tuberculosis: Biology and Infection

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“…Recombinant Plasmids and Transfection-pcDNA3-CD14, pELAM-luciferase (Luc), pTK-Renilla-Luc, pEFBOS-FLAG-MD2, pcDNA3-AU1-MyD88, pcDNA3-TRIF, pRK5-IRAK1, pcDNA3-FLAG-TRAF6, pCMV1-FLAG-TAK1, pcDNA3-HA-TAB1, pcDNA3-FLAG-p65, and pRK5-hemagglutinin (HA)-Ub-K63 only (plasmid number 17606) were described previously (22,24,29,(31)(32)(33), and pSuper-TBK1 (plasmid number 26210) was from Addgene. FLAG-Pellino-1 and pSuper vectors encoding scrambled and Pellino-1 shRNA were kindly provided by Dr. Xiaoxia Li (Lerner Research Institute, Cleveland Clinical Foundation, Cleveland, OH).…”

Section: S-[23-bis(palmitoyloxy)-(2-rs)-propyl]-n-palmitoyl-(r)-cysmentioning

confidence: 99%

“…HEK 293 cells stably expressing yellow fluorescent protein (YFP)-TLR2 (293/TLR2) or YFP-TLR4 and MD2 (293/ TLR4/MD2) were kindly provided by Dr. Douglas Golenbock (University of Massachusetts Medical School, Worcester, MA). HEK293 cells were maintained in DMEM supplemented with 10% FBS (HyClone), 2 mM L-glutamine, 100 units/ml of penicillin, and 100 g/ml of streptomycin (Life Technologies) (complete (c) DMEM), 293/TLR2, and 293/TLR4/MD2 cells were cultured in cDMEM containing 5 g/ml of puromycin or 1 mg/ml of G418, respectively (28,29). The myelomonocytic cell lines THP1 and MonoMac6 were maintained in RPMI 1640 medium supplemented with 10% FBS (HyClone), 5 ϫ 10 Ϫ5 M ␤-mercaptoethanol, 2 mM L-glutamine, 100 units/ml of penicillin, and 100 g/ml of streptomycin.…”

Section: S-[23-bis(palmitoyloxy)-(2-rs)-propyl]-n-palmitoyl-(r)-cysmentioning

confidence: 99%

Pellino-1 Positively Regulates Toll-like Receptor (TLR) 2 and TLR4 Signaling and Is Suppressed upon Induction of Endotoxin Tolerance

Murphy

Xiong

Pattabiraman

et al. 2015

Journal of Biological Chemistry

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Background: Dysregulated Toll-like receptor (TLR) signaling is a hallmark of endotoxin-tolerized macrophages in immunosuppression stages of sepsis but Pellino-1 involvement is unknown. Results: Endotoxin tolerization suppresses LPS-induced Pellino-1, Pellino-1 potentiates TLR2/4-driven NF-B, cytokines and K63-linked IRAK1, TBK1, TAK1, and TRAF6 polyubiquitination. Conclusion: Pellino-1 potentiates TLR2/4 signaling and is decreased by endotoxin tolerization. Significance: Uncovering mechanisms of endotoxin tolerance is critical to understand sepsis-associated immunosuppression.

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R753Q Polymorphism Inhibits Toll-like Receptor (TLR) 2 Tyrosine Phosphorylation, Dimerization with TLR6, and Recruitment of Myeloid Differentiation Primary Response Protein 88

Cited by 73 publications

References 78 publications

Association of Toll-like receptor 2 polymorphisms with gout

Association of Toll-like receptor 2 polymorphisms with gout

Autophagy in the Fight Against Tuberculosis

Pellino-1 Positively Regulates Toll-like Receptor (TLR) 2 and TLR4 Signaling and Is Suppressed upon Induction of Endotoxin Tolerance

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