Transcriptional regulation of prostaglandin-H-synthase-1 in the amnion-derived AV3 cell line.
Prostaglandin-H-synthase-1 (PGHS-1), while constitutively expressed in most tissues, increases in abundance in human gestational membranes at term. This suggests that PGHS-1 may be up-regulated in preparation for labor, and thus might be a key determinant in timing labor onset. We conducted transient transfection experiments in amnion-derived AV3 cells utilizing pPGHS1CAT to identify substances that might regulate PGHS-1 expression in amnion. Transforming growth factor-beta (1 ng/ml) and 15-deoxy-delta(12,14) prostaglandin J2 (1 microM) significantly (P < 0.05) (33% and 44% respectively) increased PGHS-1 promoter activity. The activity decreased significantly (P < 0.05) in response to interleukin-1 (IL-1)beta (1 ng/ml) (45%), tumor necrosis factor (TNF)-alpha (50 ng/ml) (34%), epidermal growth factor (10 ng/ml) (54%), phorbol myristate acetate (10 nM) (70%), IL-4 (10 ng/ml) (50%), IL-8 (100 ng/ml) (72%) and Activin A (25 ng/ml) (32%). Whether this degree of change in promoter activity leads to physiologically relevant alterations in the amounts of PGHS-1 present in cells remains to be determined.
Eykholt
R L
RL
Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Faculty of Medical and Health Sciences, Grafton, New Zealand. r.eykholt@auckland.ac.nz
Potter
S
S
Marvin
K W
KW
Mitchell
M D
MD
D000650:Amnion / Q000201:enzymology*; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D051545:Cyclooxygenase 1; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D011401:Promoter Regions, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D014158:Transcription, Genetic; D001616:beta-Galactosidase / Q000235:genetics
D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015500:Chloramphenicol O-Acetyltransferase; D001616:beta-Galactosidase