Chondroprotective effect of three different classes of anti-inflammatory agents on human osteoarthritic chondrocytes exposed to IL-1ß.
Int Immunopharmacol
; 28(1): 794-801, 2015 Sep.
Article
in En
| MEDLINE
| ID: mdl-26292179
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-1ß-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-1ß. The presence of IL-1ß 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-1ß. VA694, Naproxcinod and Naproxen pre-treatment were able to inhibit IL-1ß-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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrroles
/
Osteoarthritis, Hip
/
Anti-Inflammatory Agents, Non-Steroidal
/
Naproxen
/
Chondrocytes
/
Interleukin-1beta
/
Nitrates
Limits:
Aged
/
Humans
/
Middle aged
Language:
En
Journal:
Int Immunopharmacol
Journal subject:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Year:
2015
Document type:
Article