title: CSTMP Exerts Anti-Inflammatory Effects on LPS-Induced Human Renal Proximal Tubular Epithelial Cells by Inhibiting TLR4-Mediated NF-κB Pathways.
abstract: (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.
authors.affiliation: Department of Dermatology, Hainan General Hospital, Haikou, 570102, China.|Department of Dermatology, Maternal and Child Health care Hospital of Hainan Province, Haikou, 570206, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Cardiology, Hainan General Hospital, Haikou, 570102, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Liao
authors.affiliation: Department of Nephropathy, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha, 410000, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Pediatrics, Maternal and Child Health care Hospital of Hainan Province, 15 Long Kun-Nan Road, Haikou, 570206, China. xiangweihn2@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiang
authors.affiliation: Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, 410000, China.
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Lu
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D051550:I-kappa B Kinase / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000473:pathology; D008070:Lipopolysaccharides; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000473:pathology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011719:Pyrazines / Q000494:pharmacology*; D013267:Stilbenes / Q000494:pharmacology*; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D000893:Anti-Inflammatory Agents; D006861:Hydrogen Peroxide; D051550:I-kappa B Kinase; D018836:Inflammation Mediators; D053592:Interleukin-1 Receptor-Associated Kinases; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases; D053594:Myeloid Differentiation Factor 88; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011719:Pyrazines; D013267:Stilbenes; D048029:TNF Receptor-Associated Factor 6; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D000099151:MAP Kinase Kinase Kinase 7; C000613321:2-(2-chlorostyryl)-3,5,6-trimethylpyrazine; C507779:MYD88 protein, human; C498143:RELA protein, human; C495345:TLR4 protein, human; C507768:IRAK1 protein, human
keywords: CSTMP; NF-κB; TLR4; human renal proximal tubular epithelial cells; inflammatory response