Cellular Biology |
From the Laboratory of Inflammation Mediators (M.S., M.C., J.-R.E.,
L.V.), Institute of Research of Hospital Santa Creu i Sant Pau, Barcelona, and
Centro de Biología Molecular "Severo Ochoa" Centro Superior
de Investigaciones Cient
icas (M.A.I.),
Madrid, Spain.
Correspondence to Dr Luís Vila, H.S. Creu i S. Pau (Antigua Guardería), S. Antonio Ma Claret 167, 08025 Barcelona, Spain. E-mail luisvila{at}retemail.es
AbstractIn a previous work, we
postulated that endothelial cells possess only the
following 2 enzymes involved in prostanoid synthesis:
cyclooxygenase and prostacyclin synthase. The
present work focused on investigating the expression of
prostaglandin (PG) E synthase (PGES) in vascular cells.
After incubation of vascular smooth muscle cells (SMCs) and human
umbilical vein endothelial cells (HUVECs) with
[14C]arachidonic acid, the profile of
prostanoid synthesis was assessed by HPLC. Untransformed
PGH2 released by the cells was evaluated as the difference
in the formation of PGF2
in the incubations performed in
the presence and in the absence of SnCl2. Resting SMCs and
SMCs stimulated with phorbol 12-myristate 13-acetate (PMA),
lipopolysaccharide (LPS), interleukin (IL)-1ß, and tumor
necrosis factor (TNF)-
formed PGE2 and PGI2
(evaluated as 6-oxo-PGF1
), and in the presence of
SnCl2 only a small amount of PGE2 was deviated
toward PGF2
. In contrast, resting and stimulated HUVECs
produced PGI2, PGE2, PGF2
, and
PGD2, and SnCl2 completely diverted
PGE2 and PGD2 toward PGF2
.
Reverse transcriptasepolymerase chain reaction analysis shows
that mRNA encoding for PGES was not present in HUVECs and in
endothelial cells from saphenous vein. Nevertheless,
PGES was expressed in SMCs and induced by IL-1ß and TNF-
, and by
PMA and LPS, although to a lesser extent. Whereas SMC stimulation led
to an increase in the synthesis of PGE2 and
PGI2 but not of untransformed PGH2, stimulation
of endothelial cells resulted in an enhanced release of
the vasoconstricting prostanoid PGH2.
Key Words: prostaglandin E synthase endothelium smooth muscle prostanoid cytokine
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