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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:677.)
© 2000 American Heart Association, Inc.

Vascular Biology

Cyclooxygenase-2 Regulates Granulocyte-Macrophage Colony–Stimulating Factor, but Not Interleukin-8, Production by Human Vascular Cells

Role of cAMP

Salome J. Stanford; John R. Pepper; Jane A. Mitchell

From the Unit of Critical Care (S.J.S., J.A.M.) and Department of Cardiothoracic Surgery (J.R.P.), The Royal Brompton and Harefield N.H.S. Trust, Imperial College School of Medicine, London, UK.

Correspondence to Dr J.A. Mitchell, Unit of Critical Care, The Royal Brompton and Harefield N.H.S. Trust, Imperial College School of Medicine, Sydney Street, London SW3 6NP, UK. E-mail j.a.mitchell{at}ic.ac.uk

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-1ß. 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.

Key Words: inflammation • neutrophils • aspirin • interleukin-8 • atherosclerosis

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