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Functional consequences of the Asp299Gly Toll-like receptor-4 polymorphism.
van der Graaf, Chantal; Kullberg, Bart Jan; Joosten, Leo; Verver-Jansen, Trees; Jacobs, Liesbeth; Van der Meer, Jos W M; Netea, Mihai G.
Afiliación
  • van der Graaf C; Department of Medicine, University Medical Center St. Radboud Nijmegen, The Netherlands.
Cytokine ; 30(5): 264-8, 2005 Jun 07.
Article en En | MEDLINE | ID: mdl-15927851
ABSTRACT
Toll-like receptor-4 (TLR4) is a pattern-recognition receptor not only for exogenous ligands such as lipopolysaccharide (LPS) of Gram-negative bacteria, but also for endogenous ligands such as fibronectin, heat shock proteins and hyaluronan oligosaccharides. The Asp299Gly allele of the TLR4 gene has been associated with increased risk for severe infections, but reduced progression of atherosclerosis. We have investigated the consequences of the presence of Asp299Gly polymorphism after stimulation of mononuclear cells with lipopolysaccharide (LPS), the non-LPS TLR4 microbial stimuli Aspergillus fumigatus and Cryptococcus neoformans, and the endogenous TLR4 ligand heat shock protein 60. No differences in either production of the proinflammatory cytokine TNF or the antiinflammatory cytokine interleukin-10 were observed between volunteers with the wild-type allele, volunteers heterozygous for the Asp299Gly allele and one volunteer homozygous for the TLR4 variant. In conclusion, the presence of the Asp299Gly TLR4 polymorphism does not result in defective pro and antiinflammatory cytokine production after stimulation with either exogenous (LPS and non-LPS) or endogenous TLR4 ligands, and alternative explanations are likely to be responsible for the epidemiological data showing associations with inflammatory conditions. In addition, this is the first study to demonstrate that even homozygosity for the Asp299Gly mutation does not confer hyporesponsiveness to stimulation with TLR4 stimuli.
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Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Polimorfismo Genético / Glicoproteínas de Membrana / Ácido Aspártico / Receptores de Superficie Celular Límite: Adult / Humans / Middle aged Idioma: En Revista: Cytokine Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2005 Tipo del documento: Article País de afiliación: Países Bajos
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Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Polimorfismo Genético / Glicoproteínas de Membrana / Ácido Aspártico / Receptores de Superficie Celular Límite: Adult / Humans / Middle aged Idioma: En Revista: Cytokine Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2005 Tipo del documento: Article País de afiliación: Países Bajos