6533b85ffe1ef96bd12c2608

RESEARCH PRODUCT

A novel cyclo-oxygenase-2 inhibitor modulates catabolic and antiinflammatory mediators in osteoarthritis.

Francisco GomarMaría José AlcarazMaria Isabel GuillénPedro MolinaPatricia FernandezEnrique Aller

subject

MaleOxygenaseIndazolesmedicine.medical_treatmentAnti-Inflammatory AgentsOsteoarthritisPharmacologyBiochemistryOsteoarthritismedicineHumansCyclooxygenase InhibitorsProstaglandin E2AgedPharmacologyCyclooxygenase 2 InhibitorsChemistryCatabolismCartilageAnti-Inflammatory Agents Non-SteroidalInterleukinMembrane ProteinsAzepinesTriazolesmedicine.diseaseIsoenzymesInterleukin 10Cytokinemedicine.anatomical_structureCartilageBiochemistryCyclooxygenase 2Prostaglandin-Endoperoxide SynthasesFemalemedicine.drug

description

ITB (6-(p-bromophenyl)amino-7-(p-chlorophenyl)indazolo[2',3':1,5]-1,2,4-triazolo[4,3-a]-1,3,5-benzotriazepine) is a novel inhibitor of cyclo-oxygenase-2 (COX-2) with antiinflammatory activity in animal models. In the present study, we investigated the effect of this compound on the production of catabolic or antiinflammatory mediators in osteoarthritis (OA) cartilage. In OA cartilage explants, ITB inhibited the production of prostaglandin E(2) (PGE(2)), tumour necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase-13 (MMP-13) in a concentration-dependent manner, whereas nitrite was partially reduced. On the contrary, ITB increased the production of interleukin (IL)-10 and the expression of heme oxygenase-1 (HO-1). ITB inhibited the production of catabolic mediators at concentrations able to increase IL-10 and HO-1 in OA cartilage, suggesting that this compound may be useful in the prevention of cartilage degradation.

yearjournalcountryeditionlanguage
2004-01-19Biochemical pharmacology
10.1016/j.bcp.2004.03.038https://pubmed.ncbi.nlm.nih.gov/15242808