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Transcription profiling of human lpshigh and lpslow individuals to reveal interindividual variability in LPS responses


ABSTRACT: We used an unbiased approach to identify differences in gene expression that may account for the high degree of interindividual variability in inflammatory responses to LPS in the normal human population. We measured LPS-induced cytokine production ex vivo in whole blood from 102 healthy human subjects and identified individuals who consistently showed either very high or very low responses to LPS. Comparison of gene expression profiles between the lpshigh and lpslow individuals revealed 80 genes that were differentially expressed in the presence of LPS and 21 genes that were differentially expressed in the absence of LPS (p < 0.005, ANOVA). Expression of a subset of these genes was confirmed using real-time RT-PCR. These data illustrate a novel approach to the identification of factors that determine interindividual variability in innate immune inflammatory responses. Experiment Overall Design: Six whole blood samples (three high and three low responders to LPS) were selected from a cohort of 102 healthy individuals, exposed to media or LPS for 4 hours. RNA was isolated and hybridized with an Affymetrix array.

ORGANISM(S): Homo sapiens

SUBMITTER: Mark Wurfel 

PROVIDER: E-GEOD-3491 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Identification of high and low responders to lipopolysaccharide in normal subjects: an unbiased approach to identify modulators of innate immunity.

Wurfel Mark M MM   Park William Y WY   Radella Frank F   Ruzinski John J   Sandstrom Andrew A   Strout Jeanna J   Bumgarner Roger E RE   Martin Thomas R TR  

Journal of immunology (Baltimore, Md. : 1950) 20050801 4


LPS stimulates a vigorous inflammatory response from circulating leukocytes that varies greatly from individual to individual. The goal of this study was to use an unbiased approach to identify differences in gene expression that may account for the high degree of interindividual variability in inflammatory responses to LPS in the normal human population. We measured LPS-induced cytokine production ex vivo in whole blood from 102 healthy human subjects and identified individuals who consistently  ...[more]

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