Cell cycle-dependent expression of cyclooxygenase-2 in human fibroblasts.
The purpose of this investigation is to determine whether the levels of cyclooxygenase-2 (COX-2) expression are cell cycle dependent. We used a serum-starved human foreskin fibroblast model to determine changes in COX-2 mRNA, protein, and promoter activity in response to stimulation with interleukin-1b (IL-1b) and phorbol 12-myristate 13-acetate (PMA) at G0, G1, S and G2/M phases of the cell cycle. IL-1b (1 ng/ml) and PMA (100 nM) induced robust COX-2 expression in the G0 cells, and the level of COX-2 expression declined progressively after the cells had entered the cell cycle. The COX-2 mRNA level at G1, S and G2/M phases of the cell cycle was 76%, 46%, and 30% of that at G0, respectively. A 5-flanking promoter fragment of COX-2 constructed into a luciferase expression vector was transfected into cells. The promoter activity in response to PMA stimulation was significantly higher in G0 than in S phase cells. These results imply that G0 cells are the key players in inflammation and other COX-2-dependent pathophysiological processes. When the cells are in the proliferative phase, COX-2 inducibility becomes restrained probably by an endogenous control mechanism to avoid COX-2 mediated oxidative DNA damage.
Gilroy
D W
DW
Vascular Biology Research Center and Division of Hematology, Department of Medicine, University of Texas-Houston Medical School, Houston, Texas 77030-1503, USA.
Saunders
M A
MA
Sansores-Garcia
L
L
Matijevic-Aleksic
N
N
Wu
K K
KK
D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D005347:Fibroblasts / Q000166:cytology* / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins; D008954:Models, Biological; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D016196:S Phase; D012867:Skin / Q000166:cytology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D013755:Tetradecanoylphorbol Acetate