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

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

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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

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Celecoxib
Chemical activation
Anti-Inflammatory Agents
Degradation
Cyclooxygenase 2 Inhibitors

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Celecoxib potently inhibits TNFα-induced nuclear translocation and activation of NF-κB. / Tago, Megumi; Shimizu, Taeko; Tago, Kenji; Nakamura, Motohiro; Itoh, Hiroshi; Sonoda, Yoshiko; Kasahara, Tadashi.

In: Biochemical Pharmacology, Vol. 76, No. 5, 01.09.2008, p. 662-671.

Research output: Contribution to journalArticle

Tago, M, Shimizu, T, Tago, K, Nakamura, M, Itoh, H, Sonoda, Y & Kasahara, T 2008, 'Celecoxib potently inhibits TNFα-induced nuclear translocation and activation of NF-κB', Biochemical Pharmacology, vol. 76, no. 5, pp. 662-671. https://doi.org/10.1016/j.bcp.2008.06.015
Tago, Megumi ; Shimizu, Taeko ; Tago, Kenji ; Nakamura, Motohiro ; Itoh, Hiroshi ; Sonoda, Yoshiko ; Kasahara, Tadashi. / Celecoxib potently inhibits TNFα-induced nuclear translocation and activation of NF-κB. In: Biochemical Pharmacology. 2008 ; Vol. 76, No. 5. pp. 662-671.
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