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Oxaprozin-induced apoptosis on CD40 ligand-treated human primary monocytes is associated with the modulation of defined intracellular pathways

Bertolotto, Maria
Ottonello, Luciano
Dallegri, Franco
Published in Journal of Biomedicine and Biotechnology. 2009, vol. 2009, p. 478785
Abstract The modulation of CD40L activity might represent a promising therapeutic target to reduce monocyte inflammatory functions in chronic diseases, such as rheumatoid arthritis. In the present study, we investigated the possible influence of nonsteroidal anti-inflammatory drugs (NSAIDs) on CD40L-induced monocyte survival. Monocytes were isolated from buffy coats by using Ficoll-Percoll gradients. Monocyte apoptosis was evaluated by fluorescence microscopy on cytopreps stained with acridine orange or using flow cytometry analysis of Annexin-V and Propidium Iodide staining. Akt and NF-kappaB activation was assessed using western blot. Caspase 3 activity was determined spectrophotometrically. Among different NSAIDs, only oxaprozin dose-dependently increased apoptosis of CD40L-treated monocytes. Oxaprozin pro-apoptotic activity was associated with the inhibition of CD40L-triggered Akt and NF-kappaB phosphorylation and the activation of caspase 3. In conclusion, our data suggest that oxaprozin-induced apoptosis in CD40L-treated human monocytes is associated with previously unknown cyclooxygenase (COX)-independent pathways. These intracellular proteins might be promising pharmacological targets to increase apoptosis in CD40L-treated monocytes.
Keywords Anti-Inflammatory Agents, Non-Steroidal/*pharmacologyApoptosis/*drug effectsCD40 Ligand/blood/*pharmacologyCaspase 3/metabolismCyclooxygenase Inhibitors/pharmacologyHumansInflammation/bloodMitogen-Activated Protein Kinases/bloodMonocytes/cytology/*drug effects/metabolismNF-kappa B p50 Subunit/bloodPhosphatidylinositol 3-Kinases/bloodPhosphorylationPropionic Acids/*pharmacologyProstaglandin-Endoperoxide Synthases/bloodProto-Oncogene Proteins c-akt/bloodSignal Transduction
PMID: 19672323
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Research groups Biologie du myocarde (22)
L'athérosclérose et ses complications cliniques (591)
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MONTECUCCO, Fabrizio et al. Oxaprozin-induced apoptosis on CD40 ligand-treated human primary monocytes is associated with the modulation of defined intracellular pathways. In: Journal of Biomedicine and Biotechnology, 2009, vol. 2009, p. 478785. doi: 10.1155/2009/478785 https://archive-ouverte.unige.ch/unige:19974

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Deposited on : 2012-04-23

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