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

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

  • J Biomed Biotechnol. 2009;2009:478785. doi: 10.1155/2009/478785.
Fabrizio Montecucco 1 Maria Bertolotto Luciano Ottonello Alessandra Quercioli François Mach Franco Dallegri
Affiliations

Affiliation

  • 1 Division of Cardiology, Faculty of Medicine, Foundation for Medical Researches, University Hospital of Geneva, 1211 Geneva, Switzerland. fabrizio.montecucco@medecine.unige.ch
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.

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