A three base pair gene variation within the distal 5'-flanking region of the interleukin-10 (IL-10) gene is related to the in vitro IL-10 production capacity of lipopolysaccharide-stimulated peripheral blood mononuclear cells.
Interleukin-10 (IL-10) is an important multifunctional immunmodulator. There is evidence that IL-10 secretion is associated with certain genetic elements of the proximal IL-10 gene 5'-flanking region. The allelic and genotypic comparison of IL-10 expression by lipopolysaccharide (LPS)- stimulated leukocytes (PBMC) with a recently discovered distal "indel" DNA-sequence variation at - 7400 bp revealed significant inter-individual differences in the IL-10 in vitro production capacity. Homozygotes lacking the three base pairs "GGA" (- 7400del) at this gene locus are characterised by high expression of IL-10 with a median of 1690pg/ml (P <or=0.009). The allelic comparison supports this finding (P <or=0.002). Further analysis of the haplotype -7400/- 1087 showed that homozygotes for - 7400del/- 1087G may be classified as very strong IL-10 responders with a median IL-10 secretion of 2378 pg/ml (P <or=0.025). When leukocytes were stimulated in vitro by dibutyryl-cAMP or infected with Epstein-Barr virus no significant inter-individual differences between the - 7400indel alleles or genotypes and the IL-10 in vitro production capacity were observed. Our findings further the understanding of the complexity of IL-10 gene regulation in relation to defined regulatory gene variations.
Rieth
Horst
H
Sektion Humanparasitologie des Instituts für Tropenmedizin, Eberhard-Karls-Universität, Tübingen, Germany.
Mörmann
Maik
M
Luty
Adriana J F
AJ
Assohou-Luty
Constance A
CA
Roupelieva
Maria
M
Kremsner
Peter G
PG
Kube
Dieter
D
D024506:5' Flanking Region / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence / Q000235:genetics; D002478:Cells, Cultured; D003563:Cyclic CMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D014644:Genetic Variation; D005838:Genotype; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017384:Sequence Deletion / Q000276:immunology
D008070:Lipopolysaccharides; D016753:Interleukin-10; D003563:Cyclic CMP; C053441:dibutyryl cyclic-3',5'-cytidine monophosphate