Abstract
BackgroundOur aim is to study the existence of the TLR9/TGF-β1/PDGF-B pathway in healthy humans and patients with systemic lupus erythematosus (SLE), and to explore its possible involvement in the pathogenesis of lupus nephritis (LN).MethodsProtein levels of the cytokines were detected by ELISA. mRNA levels of the cytokines were analyzed by real-time PCR. MTT assay was used to test the proliferation of mesangial cells under different treatments.ResultsCompared to healthy controls (NControl = 56), levels of Toll-like receptor (TLR)9, transforming growth factor (TGF)-β1, and platelet-derived growth factor B (PDGF-B) were increased significantly in the peripheral blood of SLE patients (NSLE = 112). Significant correlations between the levels of TLR9, TGF-β1, and PDGF-B were observed in both healthy controls and SLE patients. The levels of TGF-β1 and PDGF-B were greatly enhanced by TLR9 activation in primary cell cultures. The proliferation of mesangial cells induced by the plasma of SLE patients was significantly higher than that induced by healthy controls; PDGF-B was involved in this process. The protein levels of PDGF-B homodimer correlated with the levels of urine protein in SLE patients with LN (NLN =38).ConclusionsThe TLR9/TGF-β1/PDGF-B pathway exists in humans and can be excessively activated in SLE patients. High levels of PDGF-B may result in overproliferation of mesangial cells in the kidney that are involved in the development of glomerulonephritis and LN. Further studies are necessary to identify TLR9, TGF-β1, and PDGF-B as new therapeutic targets to prevent the development of glomerulonephritis and LN.
Highlights
Our aim is to study the existence of the TLR9/transforming growth factor (TGF)-β1/platelet-derived growth factor B (PDGF-B) pathway in healthy humans and patients with systemic lupus erythematosus (SLE), and to explore its possible involvement in the pathogenesis of lupus nephritis (LN)
Increased levels of TLR9, TGF-β1, and PDGF-B in peripheral blood of SLE patients First, by measuring the levels of TLR9, TGF-β1, and PDGF-B in the peripheral blood of SLE patients, we studied the possible involvement of the TLR9/TGF-β1/ PDGF-B pathway in the pathogenesis of SLE
With the decrease in disease activity, levels of TGF-β1 (p < 0.0001; Fig. 1e) and PDGF-B (p = 0.0255; Fig. 1f) in SLE patients decreased greatly. These results suggest that TLR9, TGF-β1, and PDGF-B may be involved in the pathogenesis of SLE
Summary
Our aim is to study the existence of the TLR9/TGF-β1/PDGF-B pathway in healthy humans and patients with systemic lupus erythematosus (SLE), and to explore its possible involvement in the pathogenesis of lupus nephritis (LN). Toll-like receptor (TLR) is expressed by a number of different immune cell types [1, 2]. It recognizes hypomethylated CpG oligonucleotide-motif DNA (CpG) in bacterial genomes and signals potent inflammatory responses. Our previously published study has identified the TLR9/TGF-β1/PDGF-B pathway as a novel signaling cascade in mouse bone marrow macrophages. We reported previously that the TLR9-mediated cascade to the induction
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