title: A novel cyclo-oxygenase-2 inhibitor modulates catabolic and antiinflammatory mediators in osteoarthritis.
abstract: 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.
authors.affiliation: Departamento de Farmacología, Facultad de Farmacia, Universidad de Valencia, Avda. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fernández
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Guillén
authors.forename: Francisco
authors.initials: F
authors.lastname: Gomar
authors.forename: Enrique
authors.initials: E
authors.lastname: Aller
authors.forename: Pedro
authors.initials: P
authors.lastname: Molina
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Alcaraz
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology*; D002356:Cartilage / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007191:Indazoles / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D008565:Membrane Proteins; D010003:Osteoarthritis / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases; D014230:Triazoles / Q000494:pharmacology*
chemical_list: C484507:6-(p-bromophenyl)amino-7-(p-chlorophenyl)indazolo(2',3':1,5)-1,2,4-triazolo(4,3-a)-1,3,5-benzotriazepine; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001381:Azepines; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007191:Indazoles; D007527:Isoenzymes; D008565:Membrane Proteins; D014230:Triazoles; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases