| First Author | Wei M | Year | 2015 |
| Journal | Mol Immunol | Volume | 68 |
| Issue | 2 Pt A | Pages | 261-71 |
| PubMed ID | 26364141 | Mgi Jnum | J:233731 |
| Mgi Id | MGI:5787903 | Doi | 10.1016/j.molimm.2015.09.002 |
| Citation | Wei M, et al. (2015) Effects of ROS-relative NF-kappaB signaling on high glucose-induced TLR4 and MCP-1 expression in podocyte injury. Mol Immunol 68(2 Pt A):261-71 |
| abstractText | High glucose (HG) induced inflammation is central to progression in diabetic nephropathy (DN). Recent studies have suggested that nuclear factor-kappa B (NF-kappaB) signaling activation is associated with DN, and podocyte damage may be involved in orchestrating these effects. Therefore, the aim of this study was to investigate the effects of NF-kappaB signaling on podocytes under HG conditions. The effects of HG and NF-kappaB signaling on podocytes were assessed by CCK-8 assay, cellular NF-kappaB translocation assay, measurement of reactive oxygen species (ROS) and Western blot analysis. We found that HG reduced cell viability, activated NF-kappaB signaling and up-regulated toll-like receptor 4 (TLR4) and monocyte chemoattractant protein-1 (MCP-1). In these cells, NF-kappaB inhibition with ammonium pyrrolidinethiocarbamate (PDTC) resulted in effectively constraining TLR4 and MCP-1 up-regulation, indicating that protective effects associated with the inhibition of NF-kappaB were linked to TLR4 and MCP-1 down-regulation in podocytes. Furthermore, HG significantly increased the production of intracellular ROS. Pretreatment with N-acetyl-l-cysteine (NAC) significantly inhibited intracellular ROS generation and increased cell viability, accompanied by a significant NF-kappaB inhibition and suppression of TLR4 and inflammatory cytokine MCP-1 expression. Collectively, our novel data suggest that HG induces the over-experssion of TLR-4 and MCP-1 through a NF-kappaB-dependent signaling. NF-kappaB-mediated increased inflammation is possibly via ROS and contributes to the cell injury. These results may provide potential therapeutic target for diabetic nephropathy in the future. |
