Interleukin-1alpha stimulated prostacyclin release by increasing gene transcription of prostaglandin H synthase and phospholipase A2 in human vascular endothelial cells.
This study was conducted to evaluate the effects of interleukin-1alpha (IL-1alpha) on prostacyclin (PGI2) production in cultured human vascular endothelial cells in association with intracellular Ca2+, inositol 1,4,5-trisphosphate (IP3), and with prostaglandin H synthase (PGHS) and phospholipase A2 (PLA2) gene expression by using the competitive polymerase chain reaction (PCR) method. IL-1alpha did not increase PGI2 production for 15 min, but induced an increase of about three-fold relative to that in controls at 60 and 180 min. IL- 1alpha had no effect on intracellular Ca2+ levels throughout the experimental period. In this study, consistent with previous reports, PGHS-1 messenger RNA (mRNA) was constitutively expressed, whereas PLA2 mRNA was not. After stimulation with IL-1alpha, PLA2 mRNA level showed an eightfold increase within 15 min, and PGHS-2 mRNA level increased by 76-fold within 180 min. PGHS-1 mRNA level was increased 1.6-fold at 180 min. These results suggest the existence of regulatory mechanisms of IL-1alpha-induced PGI2 production, which involve PGHS and PLA2 gene transcription.
Toratani
A
A
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Sawada
S
S
Kono
Y
Y
Higaki
T
T
Imamura
H
H
Tada
Y
Y
Yamasaki
S
S
Sato
T
T
Komatsu
S
S
Akamatsu
N
N
Tamagaki
T
T
Nakagawa
K
K
Tsuji
H
H
Nakagawa
M
M
D001483:Base Sequence; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D018929:Cell Culture Techniques; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000032:analysis / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000187:drug effects / Q000235:genetics*; D054467:Phospholipases A2; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
D007375:Interleukin-1; D012333:RNA, Messenger; D015544:Inositol 1,4,5-Trisphosphate; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium