Cyclooxygenase-2 inhibitors prevent trinitrobenzene sulfonic acid-induced P-glycoprotein up-regulation in vitro and in vivo.

摘要: Abstract Failed medical therapy is a common problem in inflammatory bowel disease. P-glycoprotein (P-gp), an efflux pump encoded by MDR1 (ABCB1) gene can actively drugs out of cells conferring the phenotype multidrug resistance. Various studies evoked that cyclooxygenase (COX) system may be involved regulation P-gp activity. Since COX-2 isoform overexpressed colic states, we examined inhibitory effect COX-2-inhibitors on expression and function under stimulated conditions mediated trinitrobenzene sulfonic acid (TNBS) vitro , Caco-2 cells, TNBS-induced colitis mice. expressions were evaluated real-time PCR western blot. The activity was measured intracellular accumulation rhodamine123 (Rho123) Rho123 using intestinal everted loop method We showed stimulation 0.1 mM TNBS exposure for 24 h induced protein This activation reversed simultaneous COX-2-inhibitor treatment. Moreover, this reproduced vivo mice, where increased observed post intra-rectal administration. Induced could blocked oral pre-treatment with indomethacin heptyl ester (IHE) (20 mg/kg). Administration had also protective colitis. Our observations suggest inhibition contribute to improvement response finding have relevance treatment disease patients.