Involvement of different nuclear hormone receptors in butyrate-mediated inhibition of inducible NF kappa B signalling

Mol Immunol. 2007 Jul;44(15):3625-32. doi: 10.1016/j.molimm.2007.04.010. Epub 2007 May 22.


Background: NF kappa B plays a major role in the control of immune responses and inflammation. Recently, butyrate has not only been demonstrated to suppress NF kappa B activation in colorectal cancer cells, but also to modulate the activity and expression of the Peroxisome-Proliferator-Activated-Receptor gamma (PPAR gamma) and the vitamin D receptor (VDR). Therefore, we investigated a putative involvement of both receptors in butyrate-mediated inhibition of inducible NF kappa B signalling.

Results: Treatment of HT-29 cells with butyrate attenuated basal p50 as well as TNFalpha- and LPS-induced p50 and p65 NF kappa B dimer activity in the nucleus as measured by transcription factor assay. Cytosolic expression of I kappa B alpha protein was reduced by butyrate, and TNFalpha but not by LPS. Challenge of cells with the VDR antagonist ZK191732 up-regulated basal NF kappa B activity by decreasing I kappa B alpha simultaneously, while basal signalling was not influenced by the PPAR gamma inhibitor GW9662. Pre-treatment with ZK191732 reduced the inhibitory effect of butyrate on NF kappa B activation caused by TNFalpha whereas no activation was noted in transfected dominant-negative PPAR gamma mutant vector cells. Adversely, the inhibitory effect of butyrate on NF kappa B activity induced by LPS was almost reversed in dominant-negative PPAR gamma mutant cells while pre-incubation of ZK191732 did not affect butyrate-mediated attenuation of LPS-induced NF kappa B signalling.

Conclusion: These findings provide evidence for the involvement of the nuclear hormone receptors PPAR gamma and VDR in butyrate-mediated inhibition of inducible NF kappa B activation dependent on the stimulated signalling pathway. Moreover, VDR appears to play an inhibitory role in the regulation of basal NF kappa B signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Butyrates / pharmacology*
  • Cytosol / drug effects
  • DNA / metabolism
  • Dimerization
  • HT29 Cells
  • Humans
  • I-kappa B Proteins / metabolism
  • Lipopolysaccharides / pharmacology
  • NF-KappaB Inhibitor alpha
  • NF-kappa B p50 Subunit / metabolism*
  • PPAR gamma / metabolism*
  • Receptors, Calcitriol / metabolism*
  • Signal Transduction / drug effects*
  • Transcription Factor RelA / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation / drug effects
  • Up-Regulation / genetics


  • Butyrates
  • I-kappa B Proteins
  • Lipopolysaccharides
  • NF-kappa B p50 Subunit
  • NFKBIA protein, human
  • PPAR gamma
  • Receptors, Calcitriol
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • DNA