title: Effects of S/B remedy containing Scutellaria baicalensis and Bupleurum scorzonerifolfium on hepatic interleukin-6 related signal transducer and activator of transcription 3 activation in mice through cell-cell interaction.
abstract: Signal transducer and activator of transcription 3 (STAT3) plays an important role in regulating interleukin 6 (IL-6) related growth control of the liver. Our previous study demonstrated that a mixture containing Scutellaria baicalensis and Bupleurum scorzonerifolfium (S/B remedy) modulated the growth of hepatocytes during liver regeneration after 2/3 partial hepatectomy. The aim of this study was to investigate whether S/B remedy induced mouse hepatic STAT3 activation directly in hepatocytes or indirectly via non-parenchymal cell-hepatocyte interaction. Direct S/B remedy effects were studied using primarily isolated hepatocytes; while C57BL/6J mice were used to study indirect effects of S/B remedy using gadolinium chloride to deplete Kupffer cells' function. The results showed that S/B remedy and its active constituents did not directly activate growth-related signaling in primarily isolated hepatocytes. However, S/B remedy induced STAT3 and subsequently suppressor of cytokine signaling (SOCS3) activation in mouse liver and increased serum IL-6 level in a dose-dependent manner, which could be partially blocked by pretreatment with gadolinium chloride. Oligonucloetide microarray analysis from S/B remedy-treated peripheral blood leukocytes demonstrated an up-regulation of IL-6 gene expression. We conclude that S/B remedy did not directly induce STAT3 activation in vitro, but induced hepatic IL-6 related STAT3 activation through non-parenchymal cell-hepatocyte interaction in vivo. The results provide important information on the molecular mechanisms of S/B remedy for treatment of human liver diseases.
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Japan.
authors.forename: Chang-Yin
authors.initials: CY
authors.lastname: Lee
authors.forename: Jir-You
authors.initials: JY
authors.lastname: Wang
authors.forename: Tzu-Chun
authors.initials: TC
authors.lastname: Chen
authors.forename: Jeng-Kae
authors.initials: JK
authors.lastname: Jiang
authors.forename: Chi-Hao
authors.initials: CH
authors.lastname: Peng
authors.forename: Cheng-Deng
authors.initials: CD
authors.lastname: Kuo
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Chang
authors.forename: Jen-Hwey
authors.initials: JH
authors.lastname: Chiu
authors.forename: Chew-Wun
authors.initials: CW
authors.lastname: Wu
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D029972:Bupleurum / Q000737:chemistry*; D017931:DNA Primers; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000187:drug effects* / Q000378:metabolism; D031364:Scutellaria baicalensis / Q000737:chemistry*
chemical_list: D017931:DNA Primers; D010936:Plant Extracts; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse