Suppression of lipopolysaccharide-induced upregulation of toll-like             receptor 4 by emodin in mouse proximal tubular epithelial cells.
The aim of this study was to investigate the effects of emodin, the major             component of Rheum palmatum, on lipopolysaccharide (LPS)-induced toll-like receptor             4 (TLR4) expression in cultured mouse tubular epithelial cells (TECs). The TECs             were obtained from mice and incubated with LPS and/or indicated concentrations             of emodin for 24 h. Cytokeratin, α-SMA and vimentin were detected using immunohistochemistry.             The TLR4 protein level was detected by flow cytometry. TNFα and IL-6 protein levels             were measured using an enzyme-linked immunosorbent assay (ELISA). mRNA expression             of TLR4, TNFα and IL-6 was detected using a reverse-transcription polymerase chain             reaction (RT-PCR). Results showed that a concentration of 102 ng/ml LPS significantly             upregulated TLR4 mRNA and protein levels. TNFα and IL-6 mRNA and protein levels             were also increased. Emodin (at doses of 40, 20 and 10 µM) was able to inhibit             LPS-induced TLR4 protein synthesis in cultured TECs. However, TNFα and IL-6 protein             expression was decreased in cells treated with emodin at concentrations of 40             and 20 µM. These results demonstrate that an elevated expression of inflammatory             cytokines and TLR4 in cells stimulated with LPS, were simultaneously inhibited             by emodin. Emodin is therefore able to inhibit the LPS-induced expression of TLR4             in order to downregulate TNFα and IL-6 synthesis in TECs, which may contribute             to the protective effects of emodin in renal disease.
Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310007, PR China. zhuxiaolinghz@126.com
Xiao-Ling
XL
Zhu
Yong-Jun
YJ
Wang
Ya-Ζhen
YΖ
Yang
Ru-Chun
RC
Yang
Bin
B
Zhu
Ying-Ηua
YΗ
Zhang
Yi
Y
Lin
Ying
Y
Lu
Xiao-Feng
XF
Li
Kevin T
KT
O'Byrne
D000818:Animals; D002478:Cells, Cultured; D004642:Emodin / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012250:Rheum / Q000737:chemistry; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D015850:Interleukin-6; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D004642:Emodin