title: Geniposide inhibits interleukin-6 and interleukin-8 production in lipopolysaccharide-induced human umbilical vein endothelial cells by blocking p38 and ERK1/2 signaling pathways.
abstract: OBJECTIVE
  The aim of this study was to investigate the inhibitory effect of geniposide on lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and interleukin-8 (IL-8) production in human umbilical vein endothelial cells (HUVECs).
  
  
  METHODS
  Primary HUVECs were used. The mRNA/protein levels of IL-6 and IL-8 was determined by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). LPS-induced HUVEC migration and adhesion of monocytes to HUVECs were studied by monolayer wound healing experiments and monocytic cell adhesion assay, respectively. Expression of nuclear factor kappaB (NF-kappaB), inhibitory factor kappaB-alpha (IkappaB-alpha), p38 mitogen-activated protein kinase (MAPK) and ERK1/2 were determined by Western blot analysis.
  
  
  RESULTS
  Geniposide effectively inhibited LPS-induced expression of IL-6 and IL-8 in HUVECs at the transcription and translation levels. Additionally, geniposide suppressed LPS-induced HUVEC migration and U937 monocyte adhesion to HUVECs. Signal transduction studies indicate that geniposide blocked the activation of NF-kappaB, degradation of IkappaB-alpha, and phosphorylation of p38 MAPK and ERK1/2 in HUVECs challenged by LPS.
  
  
  CONCLUSIONS
  The results show that geniposide can inhibit LPS-induced IL-6 and IL-8 production in HUVECs by blocking p38 MAPK and ERK1/2 signaling pathways.
authors.affiliation: Institute of Life Sciences, Chongqing Medical University, 1 Yi Xue Yuan Road, Box 174, 400016 Chongqing, People's Republic of China. liuht1976@126.com
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Liu
authors.forename: Jun-Lin
authors.initials: JL
authors.lastname: He
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Li
authors.forename: Zhu
authors.initials: Z
authors.lastname: Yang
authors.forename: Ying-Xiong
authors.initials: YX
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Yin
authors.forename: Yu-Guang
authors.initials: YG
authors.lastname: Du
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
mesh_terms: D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors; D007202:Indicators and Reagents; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D039823:Iridoids / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects; D016328:NF-kappa B / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D020298:U937 Cells; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D000093242:Interleukin-6 Inhibitors
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D020672:I-kappa B Proteins; D007202:Indicators and Reagents; D015850:Interleukin-6; D016209:Interleukin-8; D039823:Iridoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D048051:p38 Mitogen-Activated Protein Kinases; D000093242:Interleukin-6 Inhibitors; C007835:geniposide