[Effect of the liver X receptor agonist on LPS-induced inflammatory response associated factor IRAK-4 and NF-kappaB]

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2009 Apr;25(4):293-5, 298.
[Article in Chinese]

Abstract

Aim: To investigate the effect of the activated LXR on the expression of IRAK-4 and NF-kappaB in the inflammatory response which was induced by LPS in Kupffer cells.

Methods: The Kuppfer cells were isolated from male Kunming mice by collagen perfusion in situ. These cells were divided into four groups: normal control group, LPS treatment group, LXR agonist T0901317 treatment group, LPS and T0901317 combined treatment group. The expression of LXR, IRAK-4 and NF-kappaB gene and their protein levels were detected by real time-PCR and Western blot, and the activity of NF-kappaB was observed by EMSA.

Results: The levels of LXR mRNA and protein reached the highest in T0901317 group but the lowest in LPS group. The levels of IRAK4 and NF-kappaB mRNA and protein in the combined-treatment group were evidently lower than those in LPS group. The activity of NF-kappaB reached the highest in LPS group but it was lower in the combined-treatment group and T0901317 group.

Conclusion: LXR agonists can effectively up-regulate the level of LXR gene and protein and down-regulate the levels of IRAK4 and NF-kappaB mRNA and protein expression. They can also inhibit activity of NF-kappaB.

MeSH terms

  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Drug Synergism
  • Hydrocarbons, Fluorinated / pharmacology
  • Interleukin-1 Receptor-Associated Kinases / genetics
  • Interleukin-1 Receptor-Associated Kinases / metabolism*
  • Kupffer Cells / cytology
  • Kupffer Cells / drug effects
  • Kupffer Cells / metabolism
  • Lipopolysaccharides / pharmacology*
  • Liver X Receptors
  • Male
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Orphan Nuclear Receptors / agonists*
  • Orphan Nuclear Receptors / genetics
  • Orphan Nuclear Receptors / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfonamides / pharmacology

Substances

  • Hydrocarbons, Fluorinated
  • Lipopolysaccharides
  • Liver X Receptors
  • NF-kappa B
  • Orphan Nuclear Receptors
  • RNA, Messenger
  • Sulfonamides
  • T0901317
  • Interleukin-1 Receptor-Associated Kinases