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Cytokine Profile in a Cohort of Healthy Blood Donors Carrying Polymorphisms in Genes Encoding the NLRP3 Inflammasome
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Cytokine Profile in a Cohort of Healthy Blood Donors Carrying Polymorphisms in Genes Encoding the NLRP3 Inflammasome
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Journal Article
Cytokine Profile in a Cohort of Healthy Blood Donors Carrying Polymorphisms in Genes Encoding the NLRP3 Inflammasome
2013
Overview
The NLRP3 inflammasome has been recognized as one of the key components of the innate immunity by sensing a diversity of insults. Inflammasome activation results in the maturation of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18. Increased production of IL-1β is found in patients with gain-of-function polymorphisms in genes encoding the NLRP3 inflammasome. Since approximately 5% of the Swedish population are heterozygote carriers of these combined gene variants, their impact on inflammasome status and a relationship on disease development is therefore highly relevant to study. The present study investigates levels of inflammasome-produced cytokines as a measure of inflammasome activation in healthy individuals carrying Q705K polymorphism in the NLRP3 gene combined with C10X in the CARD8 gene.
Genotyping of 1006 healthy blood donors was performed for the polymorphisms Q705K in the NLRP3 and C10X in the CARD8 genes. IL-1β, IL-18, IL-33, as well as a number of other pro-inflammatory cytokines, were analyzed by Luminex or ELISA in plasma from individuals carrying the polymorphisms and in age and gender matched non-carrier controls.
The prevalence of the polymorphisms was in line with previous studies. Plasma levels of IL-1β and IL-33 were elevated among carriers of combined Q705K+C10X polymorphisms compared to controls, whereas no difference was found for IL-18 and the other cytokines measured. Moreover, carriers of C10X or Q705K per se had similar plasma levels of IL-1β as non-carriers. These data suggest that the combined polymorphisms create inflammasomes with increased basal activation state, which might provide a more favourable innate immune response. In spite of this, it could also represent the mechanisms by which the inflammatory loop is triggered into a long-term inflammatory phenotype.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Adult
/ Age
/ Aged
/ Analysis
/ Blood
/ Boxes
/ CARD Signaling Adaptor Proteins - genetics
/ Disease
/ Enzyme-linked immunosorbent assay
/ Female
/ Gender
/ Genes
/ Genotype
/ Health
/ Humans
/ Immunity
/ Male
/ Medicin
/ Medicine
/ Mutation
/ Neoplasm Proteins - genetics
/ NLR Family, Pyrin Domain-Containing 3 Protein
/ Proteins
