title: Circulating IgA from acute stage of childhood Henoch-Schönlein purpura can enhance endothelial interleukin (IL)-8 production through MEK/ERK signalling pathway.
abstract: Recently, sera from children with active Henoch-Schönlein purpura (HSP) have been found to enhance interleukin (IL)-8 production by human umbilical venous endothelial cells (HUVEC). To further determine the possible factor with the ability to enhance endothelial IL-8 production in sera from acute stage of HSP, 10 children with HSP at the acute stage and 10 healthy controls were enrolled. IgA antiendothelial cell antibodies (AECA) were detected by cell-based ELISA. Active sera with or without pretreatment with anti-human IgA antibody, sera of controls, and immunoglobulin A (IgA) derived from sera were used to stimulate the HUVEC. The ability of these factors to enhance endothelial IL-8 production was evaluated. Furthermore, signalling pathways were also assayed by different inhibitors, and confirmed by immunoblotting. Serum levels of IgA AECA in HPS patients at the acute stage were significantly higher than in controls (P < 0.001). The active sera could enhance endothelial IL-8 production (P = 0.004, compared with control sera), and the ability of these sera was mostly abolished when pretreated with fixed anti-human IgA antibody. The supernatant IL-8 levels of endothelial cells stimulated by IgA derived from acute stage of HSP were statistically higher than controls (P < 0.001). PD98059, an inhibitor of ERK phosphorylation, significantly reduced IgA AECA-stimulated endothelial IL-8. IgA AECA also enhanced the phosphorylation of ERK1 with a time-dependent manner. Together with these findings, it is concluded that IgA AECA derived from acute stage of HSP may bind to endothelial and enhance endothelial cells to produce IL-8 via MEK/REK signalling pathway.
authors.affiliation: Department of Paediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, 7 Chung-Shan South Road, Taipei, Taiwan.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Yang
authors.forename: Y-H
authors.initials: YH
authors.lastname: Huang
authors.forename: Y-L
authors.initials: YL
authors.lastname: Lin
authors.forename: L-C
authors.initials: LC
authors.lastname: Wang
authors.forename: Y-H
authors.initials: YH
authors.lastname: Chuang
authors.forename: H-H
authors.initials: HH
authors.lastname: Yu
authors.forename: Y-T
authors.initials: YT
authors.lastname: Lin
authors.forename: B-L
authors.initials: BL
authors.lastname: Chiang
mesh_terms: D000208:Acute Disease; D001323:Autoantibodies / Q000276:immunology*; D002648:Child; D042783:Endothelial Cells / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000276:immunology; D005419:Flavonoids / Q000276:immunology; D006801:Humans; D011695:IgA Vasculitis / Q000276:immunology*; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology*; D016209:Interleukin-8 / Q000276:immunology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000276:immunology; D010766:Phosphorylation; D015398:Signal Transduction / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D001323:Autoantibodies; D005419:Flavonoids; D007070:Immunoglobulin A; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one