Inflammation, longevity, and cardiovascular diseases: role of polymorphisms of TLR4

Giuseppina Colonna Romano, Carmela Rita Balistreri, Matteo Bulati, Domenico Lio, Calogero Caruso, Giuseppina Candore, Sonya Vasto, Giuseppina Candore, Alessandra Aquino, Daniele Di Carlo, Florinda Listi', Maria Paola Grimaldi, Valentina Orlando

Risultato della ricerca: Articlepeer review

60 Citazioni (Scopus)

Abstract

The total burden of infection at various sites may affect the progression of atherosclerosis, the risk being modulated by host genotype. The role of lipopolysaccaride receptor TLR4 is paradigmatic. It initiates the innate immune response against gram-negative bacteria; and TLR4 polymorphisms, as ASP299GLY, suggested to attenuate receptor signaling, have been described. We demonstrated that TLR4ASP299GLY polymorphism shows a significantly lower frequency in patients affected by myocardial infarction compared to controls, whereas centenarians show a higher frequency. Thus, people genetically predisposed to developing weak inflammatory activity, seem to have fewer chances of developing cardiovascular diseases (CVD) and, subsequently, live longer if they do not become affected by serious infectious diseases. These results are in agreement with our other data demonstrating how genetic background may exert the opposite effect with respect to inflammatory components in CVD and longevity. In the present report, to validate this hypothesis, the levels of interleukin (IL)-6, a pro-inflammatory cytokine involved in atherosclerosis and longevity, were determined by an enzymelinked immuno-sorbent assay (ELISA) in supernatants from a whole blood assay after stimulation with subliminal doses of lipopolysaccaride (LPS) from Escherichia coli (E. coli). The samples, genotyped for the ASP299GLY polymorphism, were challenged with LPS for 4, 24, and 48 h. What we found was that Il-6 values were significantly lower in carriers bearing TLR4 mutation. Therefore, the pathogen burden, by interacting with host genotype, determines the type and intensity of the immune-inflammatory responses accountable for pro-inflammatory status, CVD, and unsuccessful aging. On the other hand, our present data seem to explain the inconclusive results obtained in case-control studies taking into account the role of functional IL-6 polymorphisms in successful and unsuccessful aging. In fact, IL6levels seem to depend, in addition, on IL-6 polymorphisms and on innate immunity gene polymorphisms as well.
Lingua originaleEnglish
pagine (da-a)282-287
Numero di pagine6
RivistaAnnals of the New York Academy of Sciences
Volume1067
Stato di pubblicazionePublished - 2006

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.1300.1300???
  • History and Philosophy of Science

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