Accelerative effect of a selective cyclooxygenase-2 inhibitor on Fas-mediated apoptosis in human neutrophils
| Autor: | Makiko Uchida, Sayaka Takaoka, Masao Nagumo, Hitoshi Watanabe, Gen Kondo, Masaru Ohashi, Masayasu Iwase |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Programmed cell death
medicine.medical_specialty Neutrophils medicine.medical_treatment Immunology Apoptosis Inflammation Granulocyte Biology Pharmacology Dinoprostone Internal medicine medicine Humans Immunology and Allergy RNA Messenger fas Receptor Prostaglandin E2 Nitrobenzenes Sulfonamides Cyclooxygenase 2 Inhibitors Interleukin medicine.anatomical_structure Endocrinology Cytokine Cyclooxygenase 2 Enzyme Induction Cytokines Tumor necrosis factor alpha medicine.symptom medicine.drug |
| Zdroj: | International Immunopharmacology. 6:334-341 |
| ISSN: | 1567-5769 |
| DOI: | 10.1016/j.intimp.2005.08.017 |
| Popis: | Inflammatory stimuli, such as cytokines, can induce cyclooxygenase-2 (COX-2) expression in neutrophils. Selective, anti-inflammatory COX-2 inhibitors have been developed for patients with acute inflammatory diseases. Recent work has shown that selective COX-2 inhibitors interfere with tumor cell growth. The purpose of this study was to examine the capability of selective COX-2 inhibitors on Fas-mediated apoptosis in cytokine-stimulated neutrophils. Tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced prostaglandin E2 (PGE2) release through the induction of COX-2 in neutrophils. This effect was not seen with either interleukin (IL)-1beta or IL-8. TNF-alpha-and GM-CSF-induced PGE2 release was blocked by the addition of the selective COX-2 inhibitor, N-(2-cyclohexyloxy-4-nitrophenyl)-methanesulfonamide (NS-398; 1 microM). GM-CSF, IL-1beta and IL-8 suppressed Fas-mediated apoptosis in neutrophils; however, this effect was not seen with TNF-alpha. The anti-apoptotic effect of cytokines on Fas-mediated neutrophil apoptosis was attenuated by the addition of NS-398 (100 microM). These results suggest that NS-398 operates via two distinct mechanisms for regulating apoptosis and COX-2 activation in neutrophils. This distinction is indicated by the difference in concentration of NS-398 required for acceleration of Fas-mediated neutrophil apoptosis, and the inhibition of PGE2 synthesis. Moreover, NS-398 suppressed the anti-apoptotic activity of IL-8 and IL-1beta, but did not induce COX-2; therefore, the pro-apoptotic mechanism of the selective COX-2 inhibitor may be unrelated to COX-2 activity. Thus, a selective COX-2 inhibitor may contribute to the reduction of acute inflammation through the enhancement of neutrophil apoptosis. |
| Databáze: | OpenAIRE |
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