CSTMP Exerts Anti-Inflammatory Effects on LPS-Induced Human Renal Proximal Tubular Epithelial Cells by Inhibiting TLR4-Mediated NF-κB Pathways.

(E)-2-(2-chlorostyryl)-3,5,6-trimethylpyrazine (CSTMP), a novel stilbene derivative, have been shown to have cytoprotective effects against H2O2-induced oxidative stress in human endothelial cells. However, little is known about its anti-inflammatory effects in lupus nephritis (LN). In the present study, we investigated the anti-inflammatory effects of CSTMP on lipopolysaccharide (LPS)-induced human renal proximal tubular epithelial cells (hRPTECs) and elucidated its molecular mechanisms. CSTMP significantly attenuated the cytotoxicity and suppressed the release of proinflammatory mediators, including iNOS, COX-2, TNF-α, IL-6, IL-8, CCL-2, ICAM-1, IL-1β, and MCP-1 in LPS-induced hRPTECs. In addition, CSTMP decreased the expression of TLR4 and its adapter molecules (MyD88, phosphorylation of TAK1, TRAF6, and IRAK1) and abolished its interactions with these adapter molecules in LPS-induced hRPTECs, resulting in an inhibition of the TLR4/MyD88/TAK1/ TRAF6/IRAK1 complex. Moreover, CSTMP also attenuated phosphorylation of IκB and IKK-α/β, and P50-NF-κB and P65-NF-κB translocation to nucleus in LPS-induced hRPTECs. These findings provided new insights to understand the mode of action of CSTMP in treatment of inflammatory diseases, such as LN.