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Mosaics of gene variations in the Interleukin-10 gene promoter affect interleukin-10 production depending on the stimulation used

Genes & Immunity volume 5, pages 246–255 (2004)Cite this article

Abstract

Interleukin-10 (IL-10), a cytokine involved in many aspects of the immune response shows interindividual variations in their expression. However, genetic variations of the 5′-flanking region of the IL-10 gene (PIL-10) are poorly characterised with respect to different stimuli. New extended haplo- and genotypes are identified present at differing frequencies in three geographically separated populations. Their influence on IL-10 expression have been assessed in vitro after stimulation of leukocytes with lipopolysaccharide (LPS), dibutyryl-cAMP or following immortalisation with Epstein–Barr virus (lymphoblastoid cell line (LCL)). Interindividual differences of IL-10 production were found to be related to single-nucleotide polymorphisms (SNP) haplotype −6752/–6208 in LCLs (P<0.02), and for haplotypes comprising SNPs –6752/-6208/-3538 after LPS stimulation (P<0.03). Carriers of the IL10.G microsatellite with 22, 24 or 26 dinucleotide repeats linked with the −1087G SNP, exhibited the highest levels of IL-10 expression. Contrasting IL-10 secretion patterns were found for IL10.R microsatellite alleles characterised by 15 dinucleotide repeats: after LPS stimulation this allele was associated with high IL-10 production (P<0.007), but with low IL-10 levels in LCLs (P< 0.038). Thus, the effects of mosaics of genetic elements in the PIL-10 on the capacity of leukocytes to produce IL-10 depend on the agent inducing IL-10 expression.

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Acknowledgements

We thank J Tomiuk and G Gallagher for helpful discussions. We are grateful to the Deutsche Forschungsgemeinschaft (DFG 954/5-1), the Tübingen fortüne Programm (658-1-0, 805-0-0), the EU INCO DEV (contract IC18CT980370) program and the Wilhelm-Sander-Stiftung for support.

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Authors and Affiliations

  1. Institut für Tropenmedizin Sektion Humanparasitologie, Eberhard-Karls-Universität Tübingen, Germany

    M Mörmann, H Rieth, C Assohou, M Roupelieva, S L Hu, P G Kremsner, A J F Luty & D Kube

  2. Medical Research Unit, Albert Schweitzer Hospital, Lambarene, Gabon

    P G Kremsner & A J F Luty

  3. Abteilung Hämatologie/Onkologie, Fachbereich Humanmedizin, Zentrum für Innere Medizin, Georg-August-Universität Göttingen, Germany

    T D Hua & D Kube

  4. Tran Hung Dao Hospital, Hanoi, Vietnam

    S L Hu

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  1. M Mörmann
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Correspondence to D Kube.

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Mörmann, M., Rieth, H., Hua, T. et al. Mosaics of gene variations in the Interleukin-10 gene promoter affect interleukin-10 production depending on the stimulation used. Genes Immun 5, 246–255 (2004). https://doi.org/10.1038/sj.gene.6364073

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