Geniposide inhibits interleukin-6 and interleukin-8 production in lipopolysaccharide-induced human umbilical vein endothelial cells by blocking p38 and ERK1/2 signaling pathways

Inflamm Res. 2010 Jun;59(6):451-61. doi: 10.1007/s00011-009-0118-3. Epub 2009 Nov 29.

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).

Materials and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors*
  • Humans
  • I-kappa B Proteins / antagonists & inhibitors
  • Indicators and Reagents
  • Interleukin-6 / antagonists & inhibitors*
  • Interleukin-6 / biosynthesis*
  • Interleukin-8 / antagonists & inhibitors*
  • Interleukin-8 / biosynthesis*
  • Iridoids / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Monocytes / drug effects
  • NF-kappa B / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • U937 Cells
  • Umbilical Veins / cytology
  • Umbilical Veins / drug effects
  • Umbilical Veins / metabolism
  • Wound Healing / drug effects
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*

Substances

  • I-kappa B Proteins
  • Indicators and Reagents
  • Interleukin-6
  • Interleukin-8
  • Iridoids
  • Lipopolysaccharides
  • NF-kappa B
  • geniposide
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases