VA694, a promising cyclooxigenase-2 (COX-2)-inhibiting hybrid drug endowed with nitric oxide (NO) releasing properties (NO-COXIB), showed COX-2-selective inhibitory effects, associated with interesting anti-inflammatory and anti-nociceptive activities. Therefore, we studied the effects of VA694 on cartilage metabolism, in comparison with Naproxcinod, a COX inhibitor and NO donor (CINOD), and Naproxen, a traditional non-steroidal-anti-inflammatory drug (NSAID) on human osteoarthritic chondrocyte cultures. IL-1β-stimulated chondrocytes showed a significant decrease in cell viability (P<0.001). VA694, Naproxcinod and Naproxen alone didn't significantly affect cell viability, while it restored cell viability in cultures stimulated by IL-1β. The presence of IL-1β determined a significant increase (P<0.001) in PGE2 levels measured by an ELISA assay, and in COX-2 and MMP-3, -9, and -13 gene expression analyzed by RT-PCR. VA694, Naproxcinod and Naproxen, at both concentrations analyzed, significantly counteracted the negative effects induced by IL-1β. VA694, Naproxcinod and Naproxen pre-treatment were able to inhibit IL-1β-induced NF-κB activation, when measured as its nuclear translocation (p50 and p65 subunits). Naproxcinod and Naproxen pre-treatment didn't affect cytoplasmic NF-κB levels; VA694 decreased the cytoplasmic levels of both subunits. Our data suggest that VA694, Naproxcinod and Naproxen, exert anti-inflammatory and chondroprotective effects on OA chondrocytes.

CHELESCHI, S., PASCARELLI, N.A., Valacchi, G., DI CAPUA, A., Biava, M., Belmonte, G., et al. (2015). Chondroprotective effect of three different classes of anti-inflammatory agents on human osteoarthritic chondrocytes exposed to IL-1β. S. Cheleschi, N. A. Pascarelli, G. Valacchi, A. Di Capua, M. Biava, G. belmonte, A. Giordani, C. Sticozzi, M. Anzini, A. Fioravanti. INTERNATIONAL IMMUNOPHARMACOLOGY, 28(1), 794-801 [10.1016/j.intimp.2015.07.003].

Chondroprotective effect of three different classes of anti-inflammatory agents on human osteoarthritic chondrocytes exposed to IL-1β. S. Cheleschi, N. A. Pascarelli, G. Valacchi, A. Di Capua, M. Biava, G. belmonte, A. Giordani, C. Sticozzi, M. Anzini, A. Fioravanti

CHELESCHI, SARA;PASCARELLI, NICOLA ANTONIO;DI CAPUA, ANGELA;Belmonte, Giuseppe;ANZINI, MAURIZIO;
2015

Abstract

VA694, a promising cyclooxigenase-2 (COX-2)-inhibiting hybrid drug endowed with nitric oxide (NO) releasing properties (NO-COXIB), showed COX-2-selective inhibitory effects, associated with interesting anti-inflammatory and anti-nociceptive activities. Therefore, we studied the effects of VA694 on cartilage metabolism, in comparison with Naproxcinod, a COX inhibitor and NO donor (CINOD), and Naproxen, a traditional non-steroidal-anti-inflammatory drug (NSAID) on human osteoarthritic chondrocyte cultures. IL-1β-stimulated chondrocytes showed a significant decrease in cell viability (P<0.001). VA694, Naproxcinod and Naproxen alone didn't significantly affect cell viability, while it restored cell viability in cultures stimulated by IL-1β. The presence of IL-1β determined a significant increase (P<0.001) in PGE2 levels measured by an ELISA assay, and in COX-2 and MMP-3, -9, and -13 gene expression analyzed by RT-PCR. VA694, Naproxcinod and Naproxen, at both concentrations analyzed, significantly counteracted the negative effects induced by IL-1β. VA694, Naproxcinod and Naproxen pre-treatment were able to inhibit IL-1β-induced NF-κB activation, when measured as its nuclear translocation (p50 and p65 subunits). Naproxcinod and Naproxen pre-treatment didn't affect cytoplasmic NF-κB levels; VA694 decreased the cytoplasmic levels of both subunits. Our data suggest that VA694, Naproxcinod and Naproxen, exert anti-inflammatory and chondroprotective effects on OA chondrocytes.
CHELESCHI, S., PASCARELLI, N.A., Valacchi, G., DI CAPUA, A., Biava, M., Belmonte, G., et al. (2015). Chondroprotective effect of three different classes of anti-inflammatory agents on human osteoarthritic chondrocytes exposed to IL-1β. S. Cheleschi, N. A. Pascarelli, G. Valacchi, A. Di Capua, M. Biava, G. belmonte, A. Giordani, C. Sticozzi, M. Anzini, A. Fioravanti. INTERNATIONAL IMMUNOPHARMACOLOGY, 28(1), 794-801 [10.1016/j.intimp.2015.07.003].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/982154
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