Biology Reference
In-Depth Information
Table 1
PDE distribution within human cells of interest for the treatment of respiratory diseases
such as asthma and COPD
Cell type
PDE4
subtype
a
Other PDE's
Biological consequence
of PDE4 inhibition
Reference
A, B, D
b
T-lymphocytes
CD4
CD8
Th1, Th2
Th17
3, 7
Inhibition of proliferation
and cytokine release
Essayan et al. (
1997
),
Gantner et al. (
1997b
),
Hatzelmann and Schudt
(
2001
), Smith et al. (
2003
),
Peter et al. (
2007
),
Ma et al. (
2008
)
B cells
A, B, D 7
Increased proliferation
Gantner et al. (
1998
),
Smith et al. (
2003
)
Eosinophils
A, B, D 7
Inhibition of superoxide
anion generation;
delayed apoptosis
Hatzelmann and Schudt
(
2001
), Smith et al. (
2003
),
Parkkonen et al. (
2007
)
Neutrophils
A, B, D 7
Inhibition of superoxide
anion and neutrophil
elastase release
Hatzelmann and Schudt
(
2001
), Smith et al. (
2003
),
Jones et al. (
2005
)
Monocyte
A, B, D 7
Inhibition of TNF
a
release
Hatzelmann and Schudt
(
2001
), Smith et al.
(
2003
), Heystek et al.
(
2003
), Jones et al. (
2005
)
Macrophages
A, B, D 1, 3, 7
Inhibition of TNF
a
release
c
Gantner et al. (
1997a
),
Hatzelmann and
Schudt (
2001
), Smith
et al. (
2003
), Barber et al.
(
2004
)
Dendritic cells
A, B, D 1, 3
Inhibition of TNF
a
release
Hatzelmann and Schudt (
2001
),
Heystek et al. (
2003
)
Osteoblast
A, B, D 3
Stimulates
RANKL-induced
osteoclast formation
Noh et al. (
2009
)
Chondrocytes
A, B, D 1
Inhibition of IL-1
b
stimulated production
of nitric oxide
Tenor et al. (
2002
)
Mast cells
Little if any mast cell
stabilization
Weston et al. (
1997
),
Shichijo et al. (
1998
)
Airway epithelial
cells
1-3, 4, 5, 7, 8
Increased production
of PGE
2
; inhibition
of IL-6 production
Fuhrmann et al. (
1999
),
Haddad et al. (
2002
)
Endothelial cells
2, 3, 4, 5
Inhibition of adhesion
molecule expression
Jones et al. (
2005
), Sanz
et al. (
2007
)
Fibroblasts
A, B, D 1, 4, 5, 7
Inhibition of fibroblast
chemotaxis;
inhibition of pro-
MMP1,2 release
Differentiation into
myofibroblasts
Kohyama et al. (
2002
),
Smith et al. (
2003
),
Martin-Chouly et al.
(
2004
), Dunkern et al.
(
2007
)
d
Sensory nerves
D
1, 3
Inhibition of
neuropeptide
release
Spina et al. (
1995
)
a
PDE4 subtype mRNA expression illustrating relative abundance in cells
b
PDE4D absent in Th1 cells
c
In the presence of a PDE3 inhibitor
d
Guinea-pig sensory nerves
