title: α-Enolase expressed on the surfaces of monocytes and macrophages induces robust synovial inflammation in rheumatoid arthritis.
abstract: α-Enolase (ENO1) is a multifunctional glycolytic enzyme expressed abundantly in the cytosol. It has been implicated in autoimmune and inflammatory diseases. Serum Abs against ENO1 were reported in rheumatoid arthritis (RA). Cell-surface expression of ENO1 has been found to be increased rapidly in response to inflammatory stimuli, but its expression and function has not been reported in RA. In this study, we show that cell-surface expression of ENO1 is increased on monocytes and macrophages isolated from RA patients but not on those from osteoarthritis patients, and Ab against ENO1 can stimulate these cells to produce higher amounts of proinflammatory mediators, such as TNF-α, IL-1 α/β, IFN-γ, and PGE(2) via p38 MAPK and NF-κB pathway. The frequency of ENO1-positive cells in synovial fluid mononuclear cells was higher than PBMCs. ENO1-positive cells were also found in the inflamed synovium from RA patients and arthritic ankle tissues of mice with collagen-induced arthritis. Taken together, these findings suggest that Abs against ENO1 present in RA sera may stimulate monocytes and macrophages expressing cell-surface ENO1 and contribute to production of proinflammatory mediators during the effector phase of synovial inflammation.
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Seyeon
authors.initials: S
authors.lastname: Bae
authors.forename: Hyemin
authors.initials: H
authors.lastname: Kim
authors.forename: Naeun
authors.initials: N
authors.lastname: Lee
authors.forename: Cheolhee
authors.initials: C
authors.lastname: Won
authors.forename: Hang-Rae
authors.initials: HR
authors.lastname: Kim
authors.forename: Young-il
authors.initials: YI
authors.lastname: Hwang
authors.forename: Yeong Wook
authors.initials: YW
authors.lastname: Song
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kang
authors.forename: Wang Jae
authors.initials: WJ
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009000:Monocytes / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D010751:Phosphopyruvate Hydratase / Q000096:biosynthesis* / Q000502:physiology; D013583:Synovial Membrane / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D003094:Collagen; C095157:ENO1 protein, human; C457379:Eno1 protein, mouse; D010751:Phosphopyruvate Hydratase