Glucocorticoid-induced leucine zipper (GILZ) mediates glucocorticoid action and inhibits inflammatory cytokine-induced COX-2 expression

Nianlan Yang, Weixi Zhang, Xing Ming Shi

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Cyclooxygenase-2 (COX-2) plays an important role in rheumatoid arthritis and therefore, has been a major target for anti-arthritis therapies. The expression of COX-2 is induced by inflammatory cytokines such as TNF-α and IL-1β, and inhibited by glucocorticoids. However, the molecular mechanisms underlying the anti-inflammatory and immune suppressive actions of glucocorticoids are not well defined. Here we report that glucocorticoid-induced leucine zipper (GILZ) mimics glucocorticoid action and inhibits inflammatory cytokine-induced COX-2 expression in bone marrow mesenchymal stem cells, the cells that have been recently implicated in the pathogenesis and progression of rheumatoid arthritis. Usinga retrovirus-mediated gene expression approach we demonstrate that overexpression of GILZ inhibits TNF-α and IL-1β-induced COX-2 mRNA and protein expression, and knockdown of GILZ by shRNA reduces glucocorticoid inhibition of cytokine-induced COX-2 expression. Consistent to these results, overexpression of GILZ also inhibits NF-κB-mediated COX-2 promoter activity. Finally, we show that GILZ inhibits COX-2 expression by blocking NF-κB nuclear translocation. Our results suggest that GILZ is a key glucocorticoid effect mediator and that GILZ may have therapeutic value for novel anti-inflammation therapies.

Original languageEnglish (US)
Pages (from-to)1760-1771
Number of pages12
JournalJournal of cellular biochemistry
Volume103
Issue number6
DOIs
StatePublished - Apr 15 2008

Keywords

  • Arthritis
  • COX-2
  • GILZ
  • Glucocorticoid
  • Mesenchymal stem cell

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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