Celecoxib potently inhibits TNFα-induced nuclear translocation and activation of NF-κB

Megumi Funakoshi-Tago, Taeko Shimizu, Kenji Tago, Motohiro Nakamura, Hiroshi Itoh, Yoshiko Sonoda, Tadashi Kasahara

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)662-671
Number of pages10
JournalBiochemical Pharmacology
Volume76
Issue number5
DOIs
Publication statusPublished - 2008 Sep 1

Keywords

  • CCL2/MCP-1
  • CXCL1/KC
  • Celecoxib
  • NF-κB
  • TNFα

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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