期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 378, 期 3, 页码 534-538出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.11.099
关键词
Prostaglandin; Peritoneal macrophage; Embryonic fibroblast; In vivo imaging; Inflammation
资金
- [NCI CA084572]
- [NCI CA123055]
- [P50 CA086306]
Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme for prostaglandin biosynthesis. Its inducible expression is regulated by complex pathways. To monitor Cox-2 transcriptional activity in vivo, we generated a knock-in mouse expressing a firefly luciferase reporter. In this study we examined, by comparing luciferase activity of Cox-2(luc/+) and Cox-2(luc/-) cells and mice, effects of prostanoid products on Cox-2 promoter transcriptional activation. In peritoneal macrophages. luciiferase induction by LPS in Cox-2(luc/-) cells was less than that of Cox-2(luc/+) cells. However, in the presence of PGE(2), induction was comparable, suggesting positive Cox-2 feedback regulation by PGE(2) Occurs for macrophages. In contrast. feedback modulation was not observed in TPA-induced Cox-2(luc/+) and Cox-2(luc/-) mouse embryonic fibroblasts (MEFs). Using non-invasive in vivo imaging, we observed negative feedback regulation of Cox-2 expression during paw inflammation in living mice. Out results suggest Cox-2 expression is regulated by cell type specific feedback mechanisms. both in Cultured cells and in living animals. (C) 2008 Elsevier Inc. All rights reserved.
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