A novel cyclo-oxygenase-2 inhibitor modulates catabolic and antiinflammatory mediators in osteoarthritis |
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| Authors: | Fernández Patricia Guillén Maria Isabel Gomar Francisco Aller Enrique Molina Pedro Alcaraz Maria José |
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| Affiliation: | Departamento de Farmacología, Facultad de Farmacia, Universidad de Valencia, Avda. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain. |
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| 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. |
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| Keywords: | COX-2, cyclo-oxygenase-2 DFU, 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone HO-1, heme oxygenase-1 IL, interleukin ITB, 6-(p-bromophenyl)amino-7-(p-chlorophenyl)indazolo[2′,3′:1,5]-1,2,4-triazolo[4,3-a]-1,3,5-benzotriazepine MMP-13, matrix metalloproteinase-13 MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide NO, nitric oxide NOS-2, nitric oxide synthase-2 OA, osteoarthritis PGE2, prostaglandin E2 TNF-α, tumour necrosis factor-α |
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