Circulating IgA from acute stage of childhood Henoch-Schönlein purpura can enhance endothelial interleukin (IL)-8 production through MEK/ERK signalling pathway
Journal
Clinical and Experimental Immunology
Journal Volume
144
Journal Issue
2
Pages
247-253
Date Issued
2006
Author(s)
Huang Y.-H.
Lin Y.-L.
Abstract
Recently, sera from children with active Henoch-Sch?nlein 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. ? 2006 British Society for Immunology.
SDGs
Other Subjects
2 (2 amino 3 methoxyphenyl)chromone; endothelial cell antibody; immunoglobulin A; immunoglobulin A antibody; interleukin 8; mitogen activated protein kinase; anaphylactoid purpura; antibody detection; article; cell stimulation; child; clinical article; controlled study; cytokine production; endothelium; enzyme linked immunosorbent assay; human; human cell; immunoblotting; priority journal; protein phosphorylation; signal transduction; Acute Disease; Autoantibodies; Child; Endothelial Cells; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Humans; Immunoglobulin A; Interleukin-8; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Phosphorylation; Purpura, Schoenlein-Henoch; Signal Transduction; Tumor Necrosis Factor-alpha
Type
journal article