title: Cyclooxygenase-2 regulates granulocyte-macrophage colony-stimulating factor, but not interleukin-8, production by human vascular cells: role of cAMP.
abstract: Vascular smooth muscle is now recognized as an important site of mediator generation under inflammatory conditions. Indeed, the release of leukocyte activators, such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-8, by human arterial smooth muscle cells has recently been demonstrated. However, the potential for venous cells to release GM-CSF has not been addressed. We have shown that human vascular smooth muscle cells express the "inflammatory" form of cyclooxygenase (COX), cyclooxygenase-2 (COX-2), when stimulated with cytokines. In some nonvascular cell types, the COX activity has been shown to regulate the release of GM-CSF and IL-8, although the nature of the isoform responsible was not addressed. We show that human venous smooth muscle cells, like their arterial counterparts, release GM-CSF after stimulation with IL-1beta. Similarly, both cell types released IL-8. Under the same conditions, we found that COX-2 activity suppressed GM-CSF, but not IL-8, release by both types of human vascular cells. Moreover, the prostacyclin mimetic, cicaprost, and the cAMP analogue, dibutyryl cAMP, inhibited GM-CSF release from these cells. These observations suggest that COX-2 activity suppresses GM-CSF release via a cAMP-dependent pathway in human vascular cells and illustrates a novel mechanism by which this enzyme can modulate immune and inflammatory events.
authors.affiliation: Unit of Critical Care, The Royal Brompton and Harefield N. H.S. Trust, Imperial College School of Medicine, London, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Stanford
authors.forename: J R
authors.initials: JR
authors.lastname: Pepper
authors.forename: J A
authors.initials: JA
authors.lastname: Mitchell
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001161:Arteriosclerosis / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D001241:Aspirin / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007189:Indans / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism* / Q000494:pharmacology; D008323:Mammary Arteries / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D000077239:Meloxicam; D008565:Membrane Proteins; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism* / Q000494:pharmacology; D012501:Saphenous Vein / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D013449:Sulfonamides / Q000494:pharmacology; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007189:Indans; D007375:Interleukin-1; D016209:Interleukin-8; D007527:Isoenzymes; C093700:L 745337; D008565:Membrane Proteins; D013449:Sulfonamides; D013843:Thiazines; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D003994:Bucladesine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011464:Epoprostenol; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; C043867:cicaprost; D001241:Aspirin; C012655:nimesulide; D000077239:Meloxicam; D007213:Indomethacin