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Original ArticleOpen Access
The Effects of COX-Metabolites on Cyclooxygenase-2 Induction in LPS-treated Endothelial Cells
Akarasereenont P 
,
Techatraisak K ,
Chotewuttakorn S ,
Thaworn A
,
Techatraisak K ,
Chotewuttakorn S ,
Thaworn A KITIRA T TECHATRAISAK, M.D., Ph.D.**,
ATHIWAT THAWORN, Cert., M.S.T.*
Cyclooxygenase (COX) is the first enzyme in the pathway in which arachidonic acid is
converted to PGs, also called COX-metabolites. COX exists as COX-I and COX-2 isoforms. Each
COX-metabolite has different characters and functions. The amounts of each COX-metabolite pro-
duced in cells are also different depending on cell type and mitogen stimulated cells. These were
thought to be autoregulation among COX-metabolites. Here, we have investigated the effects of
COX-metabolites, such as PGI
2
,
PGE
2
,
PGF
2
a
and U44069, on the induction of COX-2 in human
umbilical vein endothelial
~ells
(HUVEC) treated with LPS (1 jlg/ml). COX activity was measured
by the production of 6-keto-PGF
1
a'
PGE
2
,
PGF
2
a
and TXB
2
in the presence of exogenous arachidonic
acids (10 jlM for 10 min) using enzyme immunoassay (EIA). COX-I and COX-2 protein was mea-
sured by immunoblotting using specific antibody. PGI
2
,
PGE
2
,
PGF
2
a
or U44069, did not affect on
basal COX activity in untreated HUVEC (24 h incubation). Untreated HUVEC contained COX-I
protein but not COX-2 protein. When HUVEC were treated with LPS
(1
jlg/ml for 24 h), COX
activity and COX-2 protein was increased in a dose dependent manner. The increased COX activity
in LPS
(1
jlg/ml) treated HUVEC was inhibited with PGE
2
(0.03, 0.3 or 3 jlM), but not PGI
2
,
PGF
2
a
or U44069, in a dose dependent manner. Similary, COX-2 protein expression in LPS treated HUVEC
was also inhibited with PGE
2
,
but not PGI
2
,
PGF
2
a
or U44069, in a dose dependent manner. These
results suggested that PGE
2
,
but not PGI
2
,
PGF
2
a
or TXA
2
is a key in feedback regulation of COX-
metabolites produced in HUVEC.
Key word : COX-2, Prostaglandins, Endotoxin, Endothelium
ATHIWAT THAWORN, Cert., M.S.T.*
Cyclooxygenase (COX) is the first enzyme in the pathway in which arachidonic acid is
converted to PGs, also called COX-metabolites. COX exists as COX-I and COX-2 isoforms. Each
COX-metabolite has different characters and functions. The amounts of each COX-metabolite pro-
duced in cells are also different depending on cell type and mitogen stimulated cells. These were
thought to be autoregulation among COX-metabolites. Here, we have investigated the effects of
COX-metabolites, such as PGI
2
,
PGE
2
,
PGF
2
a
and U44069, on the induction of COX-2 in human
umbilical vein endothelial
~ells
(HUVEC) treated with LPS (1 jlg/ml). COX activity was measured
by the production of 6-keto-PGF
1
a'
PGE
2
,
PGF
2
a
and TXB
2
in the presence of exogenous arachidonic
acids (10 jlM for 10 min) using enzyme immunoassay (EIA). COX-I and COX-2 protein was mea-
sured by immunoblotting using specific antibody. PGI
2
,
PGE
2
,
PGF
2
a
or U44069, did not affect on
basal COX activity in untreated HUVEC (24 h incubation). Untreated HUVEC contained COX-I
protein but not COX-2 protein. When HUVEC were treated with LPS
(1
jlg/ml for 24 h), COX
activity and COX-2 protein was increased in a dose dependent manner. The increased COX activity
in LPS
(1
jlg/ml) treated HUVEC was inhibited with PGE
2
(0.03, 0.3 or 3 jlM), but not PGI
2
,
PGF
2
a
or U44069, in a dose dependent manner. Similary, COX-2 protein expression in LPS treated HUVEC
was also inhibited with PGE
2
,
but not PGI
2
,
PGF
2
a
or U44069, in a dose dependent manner. These
results suggested that PGE
2
,
but not PGI
2
,
PGF
2
a
or TXA
2
is a key in feedback regulation of COX-
metabolites produced in HUVEC.
Key word : COX-2, Prostaglandins, Endotoxin, Endothelium
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