MIF is under HDAC regulation

[Kofi]

Inhibiting MIF would prevent macrophages from sticking to the same place
and aggravating inflammation/promoting angiogenesis.

Biochim Biophys Acta. 2009 Nov;1793(11):1749-58. Epub 2009 Sep 10.
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Histone deacetylase inhibitors repress macrophage migration inhibitory
factor (MIF) expression by targeting MIF gene transcription through a
local chromatin deacetylation.
Lugrin J, Ding XC, Le Roy D, Chanson AL, Sweep FC, Calandra T, Roger T.
Infectious Diseases Service, Department of Medicine, Centre Hospitalier
Universitaire Vaudois and University of Lausanne, CH-1011 Lausanne,
Switzerland.

The cytokine macrophage migration inhibitory factor plays a central role
in inflammation, cell proliferation and tumorigenesis. Moreover,
macrophage migration inhibitory factor levels correlate with tumor
aggressiveness and metastatic potential. Histone deacetylase inhibitors
are potent antitumor agents recently introduced in the clinic.
Therefore, we hypothesized that macrophage migration inhibitory factor
would represent a target of histone deacetylase inhibitors. Confirming
our hypothesis, we report that histone deacetylase inhibitors of various
chemical classes strongly inhibited macrophage migration inhibitory
factor expression in a broad range of cell lines, in primary cells and
in vivo. Nuclear run on, transient transfection with macrophage
migration inhibitory factor promoter reporter constructs and
transduction with macrophage migration inhibitory factor expressing
adenovirus demonstrated that trichostatin A (a prototypical histone
deacetylase inhibitor) inhibited endogenous, but not episomal, MIF gene
transcription. Interestingly, trichostatin A induced a local and
specific deacetylation of macrophage migration inhibitory factor
promoter-associated H3 and H4 histones which did not affect chromatin
accessibility but was associated with an impaired recruitment of RNA
polymerase II and Sp1 and CREB transcription factors required for basal
MIF gene transcription. Altogether, this study describes a new molecular
mechanism by which histone deacetylase inhibitors inhibit MIF gene
expression, and suggests that macrophage migration inhibitory factor
inhibition by histone deacetylase inhibitors may contribute to the
antitumorigenic effects of histone deacetylase inhibitors.

Publication Types:
* Research Support, Non-U.S. Gov't

PMID: 19747950