A novel cyclo-oxygenase-2 inhibitor modulates catabolic and antiinflammatory mediators in osteoarthritis.
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.
Fernández
Patricia
P
Departamento de Farmacología, Facultad de Farmacia, Universidad de Valencia, Avda. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
Guillén
Maria Isabel
MI
Gomar
Francisco
F
Aller
Enrique
E
Molina
Pedro
P
Alcaraz
Maria José
MJ
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*
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