Biomedical Engineering Reference
In-Depth Information
More recently, it has been proposed that rhinoviral infection can
prevent GR nuclear translocation via an NF-
k
B-mediated process (93).
F. Reduced Histone Deacetylase Activity in COPD
We have demonstrated that alveolar macrophages of cigarette smokers have
reduced HDAC activity and reduced expression of HDAC2 and its activity
compared to cells from normal subjects whereas there is no reduction of
HDAC 1 expression (Fig. 3). This is correlated with increased in basal
and IL-l
b
-stimulated release of TNF
a
and IL-8 in alveolar macrophages
(94). The level of HDAC activity is inversely correlated with maximal TNF
a
and IL-8 production in these cells. Repression of HDAC activity can lead to
enhanced histone acetylation and increased gene expression. We have
Figure 3
Histone deacetylase expression and correlation between HDAC activity
and corticosteroid inhibitiory action in IL-l
b
-induced GM-CSF production. (A)
The localization of the expression of the HDAC1 and HDAC2 within BAL macro-
phages of nonsmokers (NS) and smokers (S) was detected by immunocytochemistry.
Histone deacetylase-2 expression selectively reduced in smokers. (B) The relative
expression of HDAC1 and HDAC2 mRNA in BAL macrophages isolated from S
and NS. GAPDH mRNA expression is used as a control for mRNA. (C) Correlation
between HDAC activity and steroid inhibitory action in IL-l
b
-induced TNF
a
production in BAL macrophages obtained from NS and S groups. Total HDAC
activity was measured by
3
H-acetic acid release from labelled histones. Inhibitory
effect of dexamethasone (Dex) in IL-l
b
-induced TNF
a
production was measured
with ELISA. (From Ref. 94.)
