title: The HLA-G genotype is associated with IL-10 levels in activated PBMCs.
abstract: Human leukocyte antigen (HLA)-G is an MHC class Ib molecule that is expressed at the feto-maternal interface during pregnancy. However, recent results have also shown that it may have important functions as an immuno-modulatory factor in adult life. Differences in the pattern of alternative splicing and in the stability of HLA-G mRNA transcripts have been associated with HLA-G polymorphisms, especially a 14 bp deletion/insertion polymorphism in the 3' untranslated region of the HLA-G gene. We have investigated the secretion of HLA-G5/soluble HLA-G1 and interleukin-10 (IL-10) in lipopolysaccharide (LPS)-activated peripheral blood mononuclear lymphocytes (PBMCs) in relation to the HLA-G 14 bp genotype. No HLA-G5/sHLA-G1 could be detected in the non-activated control PBMC culture media, and there were no significant differences among the three HLA-G 14 bp genotypes regarding IL-10 concentrations. In LPS-activated PBMC cultures, no significant differences among the three HLA-G 14 bp genotypes regarding HLA-G5/sHLA-G1 concentrations were observed. However, this was in contrast to the IL-10 levels (P=0.0004, Kruskal-Wallis test). The +14/+14 bp PBMC samples expressed higher levels of IL-10 when compared to the -14/+14 bp genotype and the -14/-14 bp genotype. Interestingly, the IL-10 G/G polymorphism at position -1082 was more frequent in the +14/+14 bp genotype (P=0.024, chi2 test). These results support an autocrine loop between HLA-G5/sHLA-G1 and IL-10 expression in activated PBMCs, which may result in higher IL-10 levels in +14/+14 bp HLA-G genotypes.
authors.affiliation: Department of Experimental and Diagnostic Medicine, University of Ferrara, Via Luigi Borsari 46, 44100 Ferrara, Italy. rbr@unife.it
authors.forename: Roberta
authors.initials: R
authors.lastname: Rizzo
authors.forename: Thomas Vauvert F
authors.initials: TV
authors.lastname: Hviid
authors.forename: Marina
authors.initials: M
authors.lastname: Stignani
authors.forename: Alessandra
authors.initials: A
authors.lastname: Balboni
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Grappa
authors.forename: Loredana
authors.initials: L
authors.lastname: Melchiorri
authors.forename: Olavio R
authors.initials: OR
authors.lastname: Baricordi
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006680:HLA Antigens / Q000097:blood / Q000235:genetics*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000097:blood / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000097:blood* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide
chemical_list: D020413:3' Untranslated Regions; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D008070:Lipopolysaccharides; D016753:Interleukin-10