title: Human leukocyte antigen-G molecules are constitutively expressed by synovial fibroblasts and upmodulated in osteoarthritis.
abstract: Human leukocyte antigen (HLA)-G molecules are nonclassical HLA class I antigens expressed as membrane bound and soluble isoforms (sHLA-G) with a restricted tissue distribution and anti-inflammatory functions. Because inflammation is involved in the pathogenesis of osteoarthritis (OA), we have analyzed the expression and production of HLA-G molecules in in vitro cultured synovial fibroblasts (SFs) from OA patients and control subjects. We have analyzed the levels of sHLA-G1 and HLA-G5 isoforms by immunoenzymatic assay (enzyme-linked immunosorbent assay) in the SF culture supernatants from six OA patients and six control subjects in 70-day in vitro cultures and after the addition of lipopolysaccharide or recombinant interleukin (IL)-10 (rIL-10). We have confirmed HLA-G modulation by cytofluorimetry and immunofluorescence. The results have demonstrated the spontaneous production of sHLA-G1 molecules by both OA and control SFs. The expression was confirmed by cytofluorimetry and immunofluorescence. OA SFs produce both sHLA-G1 and HLA-G5 molecules during the first 23 days of culture and higher levels of sHLA-G1 during the first 40 days of in vitro culture and after lipopolysaccharide or rIL-10 activation compared with control SFs. The production of HLA-G1 molecules, constitutively expressed by control and OA SFs, is significantly increased in OA, suggesting a possible mechanism to counteract the inflammation of the synovial joints.
authors.affiliation: Department of Morphology and Embryology, University of Ferrara, Ferrara, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Ongaro
authors.forename: Marina
authors.initials: M
authors.lastname: Stignani
authors.forename: Agnese
authors.initials: A
authors.lastname: Pellati
authors.forename: Loredana
authors.initials: L
authors.lastname: Melchiorri
authors.forename: Leo
authors.initials: L
authors.lastname: Massari
authors.forename: Gaetano
authors.initials: G
authors.lastname: Caruso
authors.forename: Monica
authors.initials: M
authors.lastname: De Mattei
authors.forename: Angelo
authors.initials: A
authors.lastname: Caruso
authors.forename: Olavio R
authors.initials: OR
authors.lastname: Baricordi
authors.forename: Roberta
authors.initials: R
authors.lastname: Rizzo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002469:Cell Separation; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013583:Synovial Membrane / Q000473:pathology*
chemical_list: D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D008070:Lipopolysaccharides; D016753:Interleukin-10