Journal
KIDNEY DISEASES
Volume 4, Issue 1, Pages 29-36Publisher
KARGER
DOI: 10.1159/000485622
Keywords
IgA nephropathy; TREM-1; Circulating IgA1-containing immune complexes
Categories
Funding
- National Science Foundation of China [81470945, 81670638]
- Training Program of the Major Research Plan of the National Natural Science Foundation of China [91642120]
- Capital of Clinical Characteristics and the Applied Research Fund [Z141107002514037, Z161100000516005]
- Beijing New-Star Plan of Science and Technology [Z161100004916167]
- National Key Research and Development Program of China [2016YFC0904102]
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Background: Circulating IgA1-containing immune complexes (cIgA1) were shown to play important roles in IgA nephropathy (IgAN). They could induce the release of multiple inflammatory factors, including MCP-1 and IL-6, and elevated urinary inflammatory factors were also reported in patients with IgAN, which suggested that inflammation is a major contributor to kidney injury in IgAN. After the previous identification of the upregulated release of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) by mesangial cells under cIgA1 challenge using cytokine array, in the present study, we further explored the role of TREM-1, an amplifier of inflammation, in cIgA1-induced kidney injury. Methods: In total, 35 patients with IgAN and 17 healthy controls were enrolled. The cIgA1 was isolated from plasma and used to treat cultured mesangial cells. The mRNA expression of TREM-1 as well as levels of sTREM-1, MCP-1, and IL-6 in the mesangial cell supernatant and urine samples were detected. Results: We found that cIgA1 from patients with IgAN could significantly upregulate the expression of TREM-1 in mesangial cells compared to healthy controls. The levels of.sTREM-1 were positively correlated with MCP-1 levels in the mesangial supernatant. Similarly, higher urinary levels of sTREM-1 were also observed in patients with IgAN compared to healthy controls. Moreover, IgAN patients with detectable urinary sTREM-1 presented with severe clinical and pathological manifestations, including higher IgA and lower eGFR levels, compared to patients whose urinary sTREM-1 levels were below the limit of quantification. Conclusion: Our present study suggested that TREM-1 in cIgA1 induced inflammatory kidney injury in IgAN. (c) 2018 S. Karger AG, Basel
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