Abstracts (complete list) - Wissenschaft Online

Konrad Alexander Bode, Klaus Heeg, Alexander H. Dalpke
Histone deacetylase inhibitor butyric acid of bacterial origin
as mediator of tolerance in the intestinal mucosa
Posttranslational modifications of histones by acetylation are a major mechanism to
modify chromatin structure and gene expression in eukaryotic DNA. In a recent work we
could show that histone HDAC inhibitors like trichostatin A or suberoylanilide
hydroxamic acid (SAHA) in non-apoptotic concentrations strongly inhibit the TLRinduced
cytokine expression of dendritic cells. In the present work we investigated
whether the HDAC inhibitor butyric acid, a product of the metabolism of some anaerobe
bacteria, is involved in the induction of tolerance towards the physiological bacterial
flora in the mucosa of the intestine.
We could show in bone marrow derived dendritic cells that butyric acid inhibits the
expression of several TLR induced cytokines like IL-12p40, IFN&beta and TNF&alpha on
protein (ELISA and FACS-analysis) and mRNA (real-time RT-PCR) level. Whereas TLR
stimulation resulted in transient histone H4 acetylation at selected regions of the IL-
12p40 promoter as shown by chromatin immunoprecipitation, butyric acid induced a
hyperacetylation of the whole IL-12p40 locus for a prolonged period. HDAC inhibitors
had no effects on upstream NF&kappaB activation and nuclear translocation as well as
on MAP kinase signaling (immuno-blot and gel-shift) but the binding of selected
transcription factors on the IL-12p40 promoter region were impaired in the presence of
butyric acid.
The results give evidence that butyric acid, a product of the metabolism of some
anaerobe bacteria, affects intestinal immune cells by inhibiting HDACs.