Cited by 247Genetic Associations and EpidemiologyCytokine Signaling Pathways and InteractionsImmune Response and Inflammation

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Differential regulation of interleukin-10 production by genetic and environmental factors – a twin study

Reuss, E, Fimmers, R, Kruger, A, Becker, C, Rittner, C, Höhler, T·2002·Genes & Immunity

DOI 10.1038/sj.gene.6363920

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Abstract

Interleukin-10 (IL-10) has a critical role in the regulation of immune responses. The relative contribution of genetic and environmental factors to IL-10 production is under debate. We performed a twin study in 246 monozygotic and dizygotic twins to assess the heritability of IL-10 production after LPS stimulation in whole blood. In addition, the influence of promoter single nucleotide polymorphisms (-1082, -819 and -592) on transcriptional activity and their binding to nuclear factors was studied in luciferase reporter gene and electrophoretic mobility shift assays. IL-10 production showed a genetic determination with a heritability of 0.5. Decreasing body mass index (BMI), smoking and female gender lead to decreased IL-10 production. In monocytes, the -1082A allele showed higher binding affinity to the transcription factor PU.1 resulting in decreased transcriptional activity of -1082A promoter haplotypes. Genetic determination of IL-10 secretion is probably lower than that previously reported. Fifty percent of the observed variability explained by genetic factors. Female individuals produce less IL-10 than male subjects. Environmental factors like smoking and decreasing BMI exert suppressing effects on IL-10 production. Although the -1082A allele shows higher binding affinity to the PU.1 transcription factor and lower transcriptional activity, this polymorphism probably explains only a small fraction of the observed heritability.

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Authors: Reuss, E., Fimmers, R., Kruger, A., Becker, C., Rittner, C., & Höhler, T.
Affiliations: Johannes Gutenberg University Mainz (DE)
University of Bonn (DE)
Corresponding author: Höhler, T
ORCID: Becker, C
Venue: Genes & Immunity
Publisher: Springer Science and Business Media LLC
Published: 2002-11-01
Volume: 3
Issue: 7
Pages: 407-413
ISSN: 1466-4879 (ISSN-L)
1476-5470
DOI: 10.1038/sj.gene.6363920
OpenAlex: W1985776841
Cited by: 247
References: 36
Citations by year: 2026: 1 · 2025: 2 · 2024: 6 · 2023: 4 · 2022: 7 · 2021: 4 · 2020: 7 · 2019: 3 · 2018: 10 · 2017: 9 · 2016: 8 · 2015: 17 · 2014: 14 · 2013: 10 · 2012: 16
FWCI: 6.19
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Genes and Immunity (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: IL-10, IL-10 production, heritability, genetic factors, environmental factors, monozygotic twins, dizygotic twins, promoter polymorphism, transcriptional activity, smoking, body mass index, sex differences, monocytes, lipopolysaccharide stimulation
MeSH terms: Binding Sites, Cell Line, DNA, Female, Gene Expression Regulation, Humans, Male, Monocytes, Promoter Regions, Genetic, Transcription Factors, Interleukin-10, Genes, Reporter, Twin Studies as Topic, Polymorphism, Single Nucleotide, Electrophoretic Mobility Shift Assay, In Vitro Techniques

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Differential regulation of interleukin-10 production by genetic and environmental factors – a twin study

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