Release of GM-CSF and G-CSF by human arterial and venous smooth muscle cells: differential regulation by COX-2.
In addition to their traditional contractile function, vascular smooth muscle cells can be stimulated under inflammatory conditions to release a range of potent biological mediators. Indeed, we and others have shown that human vascular smooth muscle release the colony stimulating factors (CSF) granulocyte macrophage-CSF (GM-CSF) and granulocyte-CSF (G-CSF) as well as large amounts of prostaglandins following the induction of cyclo-oxygenase-2 (COX-2), when stimulated with cytokines. Here we demonstrate, for the first time, that co-induced COX-2 activity simultaneously suppresses GM-CSF release and potentiates G-CSF release by human vascular cells. Moreover, the differential regulation of GM-CSF and G-CSF release by COX-2 was mimicked by the prostacyclin (PGI(2)) mimetic, cicaprost. These observations suggest that PGI(2), released following the induction of COX-2, differentially regulates the release of GM-CSF (suppresses) and G-CSF (potentiates) from human vascular cells.
Stanford
S J
SJ
Unit of Critical Care, The Royal Brompton and Harefield N.H.S. Trust, Imperial College School of Medicine, Sydney Street, London SW3 6NP.
Pepper
J R
JR
Mitchell
J A
JA
D001158:Arteries / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D005663:Furans / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000502:physiology*; D008565:Membrane Proteins; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D013268:Stimulation, Chemical; D014680:Veins / Q000166:cytology / Q000201:enzymology / Q000378:metabolism
C106876:5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005663:Furans; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D011465:Prostaglandins, Synthetic; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C043867:cicaprost; D007213:Indomethacin