Upregulation of COX-2 in cerebral microvascular endothelial cells by smooth muscle cell signals.

Cyclooxygenase (COX) isoform expression, intracellular localization, and function in endothelial cells from the newborn pig cerebral microvessels were investigated using COX-1- and COX-2-specific antibodies and the COX-2 inhibitor NS-398. Cerebral microvessels, microvascular endothelium, and cultured endothelial cells constitutively express both COX-1 and COX-2. NS-398 inhibits 70-90% of endothelial prostanoid production. Endothelial cells grown in noncontact coculture with smooth muscle cells for 24-48 h demonstrate a stable induction of COX-2 protein and an NS-398-sensitive increase in prostanoid synthesis. The induction of endothelial COX in mixed cell coculture is accompanied by intracellular redistribution of COX-2. In cocultured endothelial cells, COX-2 is observed in the nucleus, nuclear envelope, and cytoplasm, compared with the mainly intranuclear localization of COX-2 in cells cultured separately. No changes were observed in COX-1 protein, localized in endothelial cell cytoplasm and the nuclear envelope. These results indicate that smooth muscle cells may modify endothelial function by upregulating COX-2, which is a major functional COX isoform in cerebral microvascular endothelial cells.