title: Expression of interleukin-18, IL-18BP, and IL-18R in serum, synovial fluid, and synovial tissue in patients with rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is a chronic immunological disease, the invasive monocytes/macrophages and lymphocytes present in synovial cells and synovial tissue produce many cytokines and inflammatory mediators by paracrine signaling and plays a role in the pathological progress in RA patients. Interleukin-18 (IL-18) is a representative proinflammatory factor and displays multiple biological functions. This study was designed to investigate the expression of IL-18 and its receptor (IL-18R) and IL-18 binding protein (IL-18BP) in serum, synovial fluid, and synovial tissue of patients with RA, and to identify the pathological role of IL-18 in RA. Serum, synovial fluid, and synovial tissue were obtained from RA patients. Samples from patients with osteoarthritis and healthy people were obtained as controls. Levels of IL-18, IL-18BP, and PGE2 in serum and synovial fluid were measured by enzyme-linked immunosorbent assay. The biological activity of IL-18 in serum and synovial fluid was detected on the basis of IFN-gamma secretion from IL-18-responding human myelomonocytic KG-1 cells. NO in serum and synovial fluid was detected by Griess reaction. Expression of IL-18, IL-18BP, IL-18R, iNOS, and COX-2 mRNA and protein in synovial tissues was determined by quantitative reverse transcriptase polymerase chain reaction and Western blot. This study shows the expression levels of IL-18, IL-18R, iNOS, COX-2, and the biological activity of IL-18 in both serum and synovial fluid and tissue of patients with RA were significantly increased compared with the corresponding samples from the two control groups. In addition, expression of IL-18BP in patients with RA was decreased compared with samples from the two control groups. In conclusion, the overexpression of IL-18 and IL-18R may play an important role in the pathogenesis of RA.
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Institute of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
authors.forename: Xue-Ting
authors.initials: XT
authors.lastname: Shao
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Gu
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Wu
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Feng
authors.forename: Yun-Mei
authors.initials: YM
authors.lastname: Yang
authors.forename: Nan-Ping
authors.initials: NP
authors.lastname: Wu
authors.forename: Hang-Ping
authors.initials: HP
authors.lastname: Yao
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D015153:Blotting, Western; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis*; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000032:analysis*; D053727:Interleukin-18 Receptor alpha Subunit / Q000032:analysis*; D009000:Monocytes / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044967:Serum / Q000737:chemistry*; D013582:Synovial Fluid / Q000737:chemistry*
chemical_list: C508572:IL18R1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; C118370:interleukin-18 binding protein; D007371:Interferon-gamma; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone