The TLR4-MyD88-NF-κB pathway is involved in sIgA-mediated IgA nephropathy
Autor: | Yiming Mi, Junjun Zhang, Panfei Wang, Ruxue Guo, Ruwen Zhou, Bo Huang, Yanru Lu, Yali Zhou, Songxia Quan, Zhang-suo Liu |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
030232 urology & nephrology chemical and pharmacologic phenomena Immunofluorescence digestive system Nephropathy Pathogenesis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immune system fluids and secretions stomatognathic system Mucosal immunity medicine Humans TLR4 Receptor Cells Cultured Kidney medicine.diagnostic_test business.industry NF-kappa B food and beverages NF-κB Glomerulonephritis IGA IgA nephropathy medicine.disease Toll-Like Receptor 4 030104 developmental biology medicine.anatomical_structure chemistry Nephrology Immunology Immunoglobulin A Secretory Myeloid Differentiation Factor 88 Original Article business |
Zdroj: | Journal of Nephrology |
ISSN: | 1724-6059 1121-8428 |
Popis: | Previous studies have shown that secretory IgA (sIgA) was critically involved in IgA nephropathy (IgAN) immune responses. Toll-like receptors (TLRs), especially TLR4 which participates in mucosal immunity, may be involved in the pathogenesis of IgAN. The purpose of this study was to investigate whether sIgA and TLR4 interact to mediate kidney damage in IgAN patients. IgAN patients with positive sIgA deposition in renal tissues were screened by immunofluorescence assay. Patient salivary sIgA (P-sIgA) was collected and purified by jacalin affinity chromatography. Salivary sIgA from healthy volunteers was used as a control (N-sIgA). Expression of TLR4, MyD88, NF-κB, TNF-α, IL-6, and MCP-1 were detected in the mesangial area of IgAN patients by immunohistochemistry, the expression levels in patients with positive sIgA deposition were higher than that with negative sIgA deposition. Human renal mesangial cells (HRMCs) were cultured in vitro, flow cytometry showed that P-sIgA bound HRMCs significantly better than N-sIgA. HRMCs were cultured in the presence of sIgA (400 μg/mL) for 24 h, compared with cells cultured with N-sIgA, HRMCs cultured in vitro with P-sIgA showed enhanced expression of TLR4, increased secretion of TNF-α, IL-6, and MCP-1, and increased expression of MyD88/NF-κB. TLR4 shRNA silencing and NF-κB inhibition both reduced the ability of HRMCs to synthesize TNF-α, IL-6, and MCP-1. Our results indicate that sIgA may induce high expression of TLR4 in HRMCs and further activate downstream signalling pathways, prompting HRMCs to secrete multiple cytokines and thereby mediating kidney damage in IgAN patients. |
Databáze: | OpenAIRE |
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