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Differential regulation of interleukin-10 production by genetic and environmental factors – a twin study
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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“PU.1 is a transcription repressor that interacts with the Il10 promoter27,28.”
From The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance (2009) · cites this paper as [27]
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Cites
IL-10 inhibits cytokine production by activated macrophages
Fiorentino, D. F., Zlotnik, A., Mosmann, T. R., Howard, M., & O’Garra, A. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.147.11.3815 · Cited by 2,888
AN INVESTIGATION OF POLYMORPHISM IN THE INTERLEUKIN‐10 GENE PROMOTER
Turner, D. M., Williams, D. M., Sankaran, D., Lazarus, M. N., Sinnott, P. J., & Hutchinson, I. V. (1997) · European Journal of Immunogenetics · doi:10.1111/j.1365-2370.1997.tb00001.x · Cited by 1,706
Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes
Rousset, F., Garcia, E., Defrance, T., Péronne, C., Vezzio, N., Hsu, D. H., Kastelein, R., Moore, K. W., & Banchereau, J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.5.1890 · Cited by 1,238
Human Genetics. Problems and Approaches.
(1980) · Annals of Internal Medicine · doi:10.7326/0003-4819-93-1-163_3 · Cited by 990
Cytokine gene polymorphism in human disease: on-line databases
Bidwell, J. L., Keen, L. J., Gallagher, G. E., Kimberly, R. P., Huizinga, T. W. J., McDermott, M., Oksenberg, J. R., McNicholl, J., Pociot, F., Hardt, C., et al. (1999) · Genes and Immunity · doi:10.1038/sj.gene.6363645 · Cited by 805
Genetic control of the circulating concentration of transforming growth factor type beta1
Grainger, D. J. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.1.93 · Cited by 754
Llorente, L., Zou, W., Lévy, Y., Richaud‐Patín, Y., Wijdenes, J., Alcocer-Varela, J. C., Morel-Fourrier, B., Brouet, J. C., Alarcón-Segovia, D., Galanaud, P., et al. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.3.839 · Cited by 540
Properties and Functions of Interleukin-10
Mosman, T. R. (1994) · Advances in immunology · doi:10.1016/s0065-2776(08)60449-6 · Cited by 495
Interleukin 10 secretion in relation to human IL-10 locus haplotypes
Eskdale, J., Gallagher, G. E., Verweij, C. L., Keijsers, V., Westendorp, R. G. J., & Huizinga, T. W. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9465 · Cited by 466
Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1
Zhang, P., Behre, G., Pan, J., Iwama, A., Wara-aswapati, N., Radomska, H. S., Auron, P. E., Tenen, D. G., & Sun, Z. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.15.8705 · Cited by 459
Edwards-Smith, C. J., Jonsson, J. R., Purdie, D. M., Bansal, A. S., Shorthouse, C., & Powell, E. E. (1999) · Hepatology · doi:10.1002/hep.510300207 · Cited by 403
Predominant role of tumor necrosis factor- alpha in human monocyte IL-10 synthesis.
Wanidworanun, C., & Strober, W. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.12.6853 · Cited by 389
Gibson, A., Edberg, J. C., Wu, J., Westendorp, R. G. J., Huizinga, T. W. J., & Kimberly, R. P. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.6.3915 · Cited by 384
Katschke, K. J., Rottman, J. B., Ruth, J. H., Qin, S., Wu, L., LaRosa, G. J., Ponath, P. D., Park, C. C., Pope, R. M., & Koch, A. E. (2001) · Arthritis & Rheumatism · doi:10.1002/1529-0131(200105)44:5 · Cited by 287
Self-citationVogel, F., & Motulsky, A. G. (1997) · Springer eBooks · doi:10.1007/978-3-662-03356-2 · Cited by 278
Interleukin-10 level in sputum is reduced in bronchial asthma, COPD and in smokers
Takanashi, S., Hasegawa, Y., Kanehira, Y., Yamamoto, K., Fujimoto, K., Satoh, K., & Okamura, K. (1999) · European Respiratory Journal · doi:10.1034/j.1399-3003.1999.14b12.x · Cited by 229
T cell-derived IL-10 antagonizes macrophage function in mycobacterial infection
Murray, P. J., Wang, L., Onufryk, C., Tepper, R. I., & Young, R. A. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.1.315 · Cited by 225
Eskdale, J., Keijsers, V., Huizinga, T. W. J., & Gallagher, G. E. (1999) · Genes and Immunity · doi:10.1038/sj.gene.6363656 · Cited by 217
Kube, D., Platzer, C., von Knethen, A., Straub, H., Bohlen, H., Hafner, M., & Tesch, H. (1995) · Cytokine · doi:10.1006/cyto.1995.1001 · Cited by 216
Genetic influence on cytokine production in meningococcal disease
Westendorp, R., Langermans, J. A. M., Huizinga, T. W. J., Verweij, C. L., & Sturk, A. (1997) · The Lancet · doi:10.1016/s0140-6736(05)63910-4 · Cited by 179
Association between polymorphisms at the human IL‐10 locus and systemic lupus erythematosus
Eskdale, J., Wordsworth, P., Bowman, S., Field, M., & Gallagher, G. E. (1997) · Tissue Antigens · doi:10.1111/j.1399-0039.1997.tb02812.x · Cited by 175
The role of parvovirus B19 in the pathogenesis of giant cell arteritis: A preliminary evaluation
Gabriel, S. E., Espy, M. J., Erdman, D. D., Björnsson, J., Smith, T. F. A., & Hunder, G. G. (1999) · Arthritis & Rheumatism · doi:10.1002/1529-0131(199906)42:6 · Cited by 156
Interleukin-10 level in sputum is reduced in bronchial asthma, COPD and in smokers
Takanashi, S., Hasegawa, Y., Kanehira, Y., et al. (1999) · European Respiratory Journal · doi:10.1183/09031936.99.14230999 · Cited by 156
A polymorphic dinucleotide repeat in the human IL-10 promoter
Eskdale, J., & Gallagher, G. E. (1995) · Immunogenetics · doi:10.1007/bf00179416 · Cited by 151
High Levels Of Interleukin-10 During The Initial Phase Of Fulminant Meningococcal Septic Shock
Derkx, B., Marchant, A., Goldman, M., Bijlmer, R. P. G. M., & van Deventer, S. J. H. (1995) · The Journal of Infectious Diseases · doi:10.1093/infdis/171.1.229 · Cited by 136
van der Linden, M. W., Huizinga, T. W. J., Stoeken, D.-J., Sturk, A., & Westendorp, R. G. J. (1998) · Journal of Immunological Methods · doi:10.1016/s0022-1759(98)00108-2 · Cited by 130
B-Cell-Derived IL-10: Production and Function
Burdin, N., Rousset, F., & Banchereau, J. (1997) · Methods · doi:10.1006/meth.1996.0393 · Cited by 115
A second polymorphic dinucleotide repeat in the 5′ flanking region of the human IL10 gene
Eskdale, J., Kube, D., & Gallagher, G. E. (1996) · Immunogenetics · doi:10.1007/s002510050174 · Cited by 106
Crépieux, P., Coll, J., & Stéhelin, D. (1994) · PubMed · Cited by 103
New polymorphisms in the IL-10 promoter region
D’Alfonso, S., Rampi, M., Rolando, V., Giordano, M., & Momigliano‐Richiardi, P. (2000) · Genes and Immunity · doi:10.1038/sj.gene.6363666 · Cited by 102
Bienvenu, J., Doche, C., Gutowski, M. C., Lenoble, M., Lepape, A., & Perdrix, J.-P. (1995) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199500252-00017 · Cited by 93
Autocrine Induction of the Human Pro-IL-1β Gene Promoter by IL-1β in Monocytes
Toda, Y., Tsukada, J., Misago, M., Kominato, Y., Auron, P. E., & Tanaka, Y. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.4.1984 · Cited by 67
van Furth, A. M., Seijmonsbergen, E. M., Langermans, J. A. M., Groeneveld, P. H. P., de Bel, C. E., & van Furth, R. (1995) · Clinical Infectious Diseases · doi:10.1093/clinids/21.1.220 · Cited by 59
Nieters, A., Brems, S., & Becker, N. (2001) · Human Genetics · doi:10.1007/s004390100464 · Cited by 56
Repression of I-Aβ Gene Expression by the Transcription Factor PU.1
Borràs, F. E., Lloberas, J., Maki, R. A., & Celada, A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.41.24385 · Cited by 40
Rioux, N., & Castonguay, A. (2001) · Cancer Immunology Immunotherapy · doi:10.1007/s002620000157 · Cited by 19
Harendza, S., Lovett, D. H., & Stahl, R. A. K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001322200 · Cited by 17
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The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance
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Transcription of the IL10 gene reveals allele-specific regulation at the mRNA level
Kurreeman, F. A. S., Schonkeren, J. J. M., Heijmans, B. T., Toes, R. E. M., & Huizinga, T. W. J. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh187 · Cited by 262
Cell type-specific regulation of IL-10 expression in inflammation and disease
Hedrich, C. M., & Bream, J. H. (2010) · Immunologic Research · doi:10.1007/s12026-009-8150-5 · Cited by 228
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de Craen, A. J. M., Posthuma, D., Remarque, E. J., van den Biggelaar, A. H. J., Westendorp, R. G. J., & Boomsma, D. I. (2005) · Genes and Immunity · doi:10.1038/sj.gene.6364162 · Cited by 187
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Schaaf, B., Boehmke, F., Esnaashari, H., Seitzer, U., Kothe, H., Maass, M., Zabel, P., & Dalhoff, K. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200210-1164oc · Cited by 179
Metadata
- 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
- Published
- 2002-11-01
- Volume
- 3
- Issue
- 7
- Pages
- 407-413
- ISSN
- 1466-4879 (ISSN-L)
- 1476-5470
- 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
- 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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