Lys694Arg polymorphism leads to blunted responses to LPS by interfering TLR4 with recruitment of MyD88.

Innate Immunity
Yajie YangHao Fang

Abstract

TLR4 polymorphisms such as Asp299Gly and Thr399Ile related to Gram-negative sepsis have been reported to result in significantly blunted responsiveness to LPS. Our study group previously screened other TLR4 polymorphic variants by checking the NF-κB activation in comparison to wild type (WT) TLR4 in human embryonic kidney 293T cells. In this study, we found that the Lys694Arg (K694R) polymorphism reduced the activation of NF-κB, and the production of downstream inflammatory factors IL-1, TNF-α and IL-6, representing the K694R polymorphism, led to blunted responsiveness to LPS. Then, we examined the influence of the K694R polymorphism on total and cell-surface TLR4 expression by Western blotting and flow cytometry, respectively, but observed no differences between the K694R polymorphism and WT TLR4. We also used co-immunoprecipitation to determine the interaction of the K694R polymorphism and WT TLR4 with their co-receptor myeloid differentiation factor 2 (MD2) and their downstream signal adaptor MyD88. We found that K694R reduced the recruitment of MyD88 in TLR4 signalling but had no impact on the interaction with MD2.

References

Jun 11, 2002·Nature Immunology·Yoshinori NagaiKensuke Miyake
Mar 5, 2003·European Journal of Immunology·Christoph KalisMarina A Freudenberg
Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Prasad RallabhandiStefanie N Vogel
Sep 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cynthia L LeaphartDavid J Hackam
Dec 9, 2010·Journal of Periodontology·Nurcan BuduneliAyşe Nalbantsoy
Jan 12, 2011·Annual Review of Immunology·Jean-Laurent CasanovaLluis Quintana-Murci
Apr 5, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Leandra FigueroaAndrei E Medvedev
Apr 9, 2013·Expert Review of Vaccines·Lin H ChenMary E Wilson
May 18, 2013·Nature Reviews. Immunology·Luke A J O'NeillAndrew G Bowie
Jun 12, 2013·Frontiers in Bioscience (Landmark Edition)·Rong HuYu Sun
May 29, 2014·Clínica e investigación en arteriosclerosis : publicación oficial de la Sociedad Española de Arteriosclerosis·Marijke A de VriesManuel Castro Cabezas
Jun 22, 2014·Molecular Immunology·Marco Di Gioia, Ivan Zanoni
Oct 22, 2014·Cellular and Molecular Life Sciences : CMLS·Agnieszka PłóciennikowskaKatarzyna Kwiatkowska
Jan 13, 2015·F1000prime Reports·Jacques Deguine, Gregory M Barton
Mar 19, 2015·Immunologic Research·Mamoona Noreen, Muhammad Arshad
Apr 18, 2015·American Journal of Physiology. Gastrointestinal and Liver Physiology·Matthew GargusAnisa Shaker
Aug 22, 2015·Scientific Reports·Emine Guven-MaiorovRuth Nussinov
Oct 16, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shuhong GuoThomas Y Ma
Jul 28, 2017·Scientific Reports·Tikam Chand DakalNikolay V Dokholyan
Sep 12, 2018·Annual Review of Microbiology·Xiaojun TanZhijian J Chen
May 31, 2019·Nature Reviews. Microbiology·Brent W Simpson, M Stephen Trent

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Citations

Oct 15, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Natticha SumneangNipon Chattipakorn

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Methods Mentioned

BETA
co-immunoprecipitation
flow cytometry
transfection
Assay
protein assay
PCR

Software Mentioned

Image J
FlowJo V
Polyphen
GraphPad Prism
GraphPad
SIFT
Blast

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