Interleukin-17 promotes the production of underglycosylated IgA1 in DAKIKI cells

Autor: Jia-Ru Lin, Ji Wen, Hui Zhang, Li Wang, Fang-Fang Gou, Man Yang, Jun-Ming Fan
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Renal Failure, Vol 40, Iss 1, Pp 60-67 (2018)
Druh dokumentu: article
ISSN: 0886-022X
1525-6049
0886022X
DOI: 10.1080/0886022X.2017.1419972
Popis: 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) + IL-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-AZA + IL-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.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje