Role of TLR4 Polymorphisms in Inflammatory Responses Implications for Unsuccessful Aging

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21 Citazioni (Scopus)

Abstract

The total burden of infection at various sites may affect the progression of atherosclerosis and Alzheimer’s disease (AD), the risk being modulated by host genotype. The role of lipopolysaccharide (LPS) receptor TLR4 is paradigmatic. It initiates the innate immune response against gram-negative bacteria, and TLR4 single nucleotide polymorphisms (SNPs), such as +896A/G, known to attenuate receptor signaling, have been described. This SNP shows a significantly lower frequency in patients affected by myocardial infarction or AD. Thus,people genetically predisposed to developing lower inflammatory activity seem to have less chance of developing cardiovascular disease (CVD) or AD. In the present report, to validate this hypothesis, the levels of the eicosanoids, leukotriene B4 (LTB4) and prostaglandin E2 (PGE2), known to be involved as mediators in age-related diseases, were determinedby an enzyme-linked immunosorbent assay in supernatants from a whole blood assay, after stimulation with subliminal doses of LPS from Escherichia coli. The samples, genotyped for the +896A/G SNP, were challenged withLPSfor 4, 24, and 48 h. BothLTB4andPGE2values were significantly lower in carriers bearing the TLR4mutation. Therefore, the pathogen burden, by interacting with the host genotype, determines the type and intensity of the inflammatory responses accountable for proinflammatory status, CVD, AD, and unsuccessful aging (i.e., age-related inflammatory diseases).
Lingua originaleEnglish
pagine (da-a)203-207
Numero di pagine5
RivistaAnnals of the New York Academy of Sciences
Volume1119
Stato di pubblicazionePublished - 2007

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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