OBJECTIVE: To determine the in-vitro effects of several non-steroidal antiinflammatory drugs and the glucocorticoid @entity619 on the IL-1 altered expression and activity of @entity29626 , @entity31033 and @entity55618 by @entity291 articular chondrocytes. DESIGN: @entity291 chondrocytes were cultured in alginate gel beads. Cells were treated with @entity28283 in the presence of vehicle or drugs at various concentrations. After 48 h mRNA expression of @entity29626 , @entity31033 , and of the tissue inhibitor of metalloproteinases ( @entity55618 ) was analysed by RT-PCR-ELISA. The protein synthesis of @entity55618 and @entity31033 was determined by immunoprecipitation. The activity of enzymes and inhibitors was measured by functional assays. RESULTS: IL-1 increased the expression and activity of MMPs. In contrast, TIMP activity remained unchanged although @entity55618 expression was down-regulated. All tested NSAIDs and @entity619 inhibited collagenase activity induced by IL-1. Transcript levels of @entity29626 , however, were only reduced by @entity3352 , @entity9213 , @entity1623 and @entity619 . Proteoglycanase activity was only reduced by @entity3352 , @entity9213 and @entity619 . These effects were pre-translational as confirmed by immunoprecipitation. The IL-1 decreased expression of @entity55618 was further reduced by @entity619 , which resulted in a significant loss of TIMP activity. No effects on TIMP activity or @entity55618 biosynthesis were observed after treatment of chondrocytes with NSAIDs. CONCLUSION: Our studies clearly demonstrate that marked differences exist between individual NSAIDs with respect to their ability to modulate the imbalance between proteases and inhibitors during OA and RA, suggesting that the respective modes of action are independent of the inhibition of cyclooxygenases. Due to their co-regulation of MMPs and TIMP(s) glucocorticoids should be carefully studied for their overall effect on ECM proteolysis.

Effects of non-steroidal antiinflammatory drugs and @entity619 on the activity and expression of @entity29626 by XXXX articular chondrocytes.

@entity291 :: ('9913', 'Species') :: ['bovine', 'Bovine'] @entity31033 :: ('281309(Tax:9913)', 'Gene') :: ['MMP-3'] @entity28283 :: ('281250(Tax:9913)', 'Gene') :: ['IL-1alpha'] @entity619 :: ('MESH:D003907', 'Chemical') :: ['dexamethasone'] @entity9213 :: ('MESH:C065757', 'Chemical') :: ['meloxicam'] @entity1623 :: ('MESH:D009288', 'Chemical') :: ['naproxen'] @entity3352 :: ('MESH:D007213', 'Chemical') :: ['indomethacin'] @entity55618 :: ('282092(Tax:9913)', 'Gene') :: ['TIMP-1'] @entity29626 :: ('281308(Tax:9913)', 'Gene') :: ['MMP-1']
@entity291 :: (9913,Species) :: ['bovine']
