Therefore, it is still challenging to develop new and specific th

Therefore, it is still challenging to develop new and specific therapies for UC. Several researches have reported that COX-2 inhibitors may exacerbate the inflammation of colitis with mice. 5-LOX inhibitors were superior to placebo in remission maintenance in ulcerative colitis, but failed to show that selleck products it was better than placebo. The possible reason is that COX-2 and 5-LOX are co-expression and up-regulated consistently increased in inflamed tissue of UC. COX-2 and 5-LOX pathways have converging function in inflammation. Inhibition of one pathway may lead to a shunt of arachidonic acid metabolism towards another pathway. SASP, an anti-inflammatory drug that has been used in the treatment

of IBD for more than 50 years. It suppresses arachidonic acid (AA) metabolism and eicosanoids formation. However, the particular mechanism is unclear. SASP is now recognized as a ligand for PPARγ. By promoting PPARγ. Expression and its nuclear translocation, 5-ASA of SASP interfered with the NF-KB pathway by reducing NF-kB P65 translocation/activation. There was a good correlation among the expression of COX-2, 5-LOX, PPARγ and NF-kB P65. IL-13 and IL-8 are important proinflammatory

cytokines. They have good collelation with PPARγ and. AA metabolism and the activity of UC. We have found that higher expression Doxorubicin ic50 of COX-2, 5-LOX mRNA and protein was related to development of UC in foregoing study. They may play a more pivotal role in inflammation of UC. Regulating mechanisms of COX-2 and 5-LOX may be resembled. Therefore, we hypothesized that 5-ASA simultaneous inhibitor COX-2 and 5-LOX pathways could activation of PPARγ, inhibit NF-kB and suppress intestinal inflammation DSS-induced colitis, it might represent a new class of anti-inflammatory agents in UC. The purposes of this study are to observe the effects of celecoxib, AA861 and 5-ASA on dextran sulphate sodium-induced colitis experiment with mice via PPAR and NF-kappaB transduction pathway, and to investigate whether there exists a relationship between COX-2 and 5-LOX pathway, and whether dual inhibition of COX-2 and 5-LOX has a better effect

on the dextran sulphate sodium (DSS)-induced colitis experiment 上海皓元 with mice. Methods: Setting up colitis models with six to eight weeks healthy female Balb/c mice and dividing in five groups: negetive control group, DSS-induced model group, celecoxib interfering group; AA861 interfering group and SASP interfering group respectively. The effects of each group were assessed by gross and histopathological examination. Immunohistochemistry study for the expression of 5-LOX, COX-2, PPARγ and NF-kB P65 in colonic mucosa of DSS-induced colitis. Western blotting for the expression of 5-LOX, COX-2, PPARγ. 和 NF-kB P65 in colonic mucosa of DSS-induced colitis. ELASA for the expression of PGE2, LTB4, IL-13 and IL-8 in the supernatant of mucosa for DSS-induced colitis.

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