Journal
RENAL FAILURE
Volume 40, Issue 1, Pages -Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/0886022X.2017.1419972
Keywords
Interleukin 17; IgA nephropathy; C1GALT1; Cosmc; underglycosylation; IgA1
Categories
Funding
- National Natural Science Foundation of China [81170667]
- Youth Science and Technology Support Program of Sichuan Province [2011JDT0014]
- Affiliated Hospital of Sichuan Medical University
- Sichuan Medical University
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Background: Interleukin 17 (IL-17) plays an important role in the pathogenesis of autoimmune diseases and might be associated with IgA nephropathy (IgAN). This study aimed to investigate the effect of IL-17 on autoimmune pathogenesis in IgA nephropathy. Methods: DAKIKI cells were cultured and stimulated with IL-17 to perform dose-dependent and time-dependent experiments. Cell proliferation was examined by cell counting and the Cell Counting Kit-8 (CCK-8) assay. The IgA concentration and the degree of galactosylation in the supernatant were tested using ELISA and a helix aspersa (HAA) lectin binding assay, respectively. To study the mechanism of O-glycosylation, cells were stimulated with IL-17, lipopolysaccharide (LPS) or 5-azacytidine (5-AZA) thornIL-17 for 48 h, and the levels of C1GALT1 and its molecular chaperone Cosmc were measured by western blot and real-time PCR. Results: The cell counting and CCK-8 results suggested that B lymphocyte proliferation increased significantly with increased IL-17 concentration. IL-17 affected the quantity of IgA1 and its glycosylation status. HAA revealed that IL-17 promoted IgA1 underglycosylation. Mechanistically, the expression of C1GALT1 and Cosmc was significantly lower in cells stimulated by IL-17 or LPS than in the 5-AZAthornIL-17 or the control group. Conclusions: Our results suggested that IL-17 stimulates B lymphocyte to promote B-cell proliferation, which leads to increased IgA1 production in vitro accompanied by underglycosylation of IgA1. The molecular mechanism for the IgA1 underglycosylation induced by IL-17 was similar to that of LPS; however, 5-AZA inhibited IgA1 underglycosylation. IL-17 might participate in IgAN pathogenesis by influencing the production and glycosylation of IgA1 in B-cells.
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