کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2514762 | 1118482 | 2008 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Celecoxib potently inhibits TNFα-induced nuclear translocation and activation of NF-κB Celecoxib potently inhibits TNFα-induced nuclear translocation and activation of NF-κB](/preview/png/2514762.png)
Celecoxib is a specific inhibitor of cyclooxygenase 2 (COX2). While it has been used for the treatment of chronic inflammatory conditions, including rheumatoid arthritis, its detailed anti-inflammatory mechanism has not been clarified. Here, we found that Celecoxib potently inhibited TNFα-induced transcriptional activity and DNA binding activity of NF-κB; however, Celecoxib had no effect on TNFα-induced IKK activation and degradation of IκBα and IκBβ, suggesting that it inhibited NF-κB activation via suppressing downstream of IKK activation and IκBs degradation. Interestingly, it was also found that Celecoxib abrogated TNFα-induced nuclear accumulation of the NF-κB p65 subunit. As a result, TNFα-induced expression of inflammatory cytokines, CXCL1/KC and CCL2 /MCP-1, was clearly inhibited by Celecoxib. On the other hand, Celecoxib had no effect on the TNFα-induced nuclear translocation of c-jun and activation of ERK, JNK, p38 and Akt. Taken together, these data indicate that Celecoxib specifically inhibits TNFα-induced NF-κB activation at the level of its nuclear translocation. This negative regulation of NF-κB activation by Celecoxib might be an important mechanism leading to its anti-inflammatory activity.
Journal: Biochemical Pharmacology - Volume 76, Issue 5, 1 September 2008, Pages 662–671