Myeloid differentiation factor 88-dependent transcriptional regulation of cyclooxygenase-2 expression by CpG DNA

Role of NF-κB and p38

Seon Ju Yeo, Demetrius Gravis, Jae Geun Yoon, Ae-Kyung Yi

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

CpG DNA induces macrophage cyclooxgenase-2 (Cox-2) production. In this study, we have investigated a biochemical signaling pathway and transcription factors responsible for transcriptional regulation of the Cox-2 gene expression induced by CpG DNA. CpG DNA-induced Cox-2 promoter activity was completely inhibited by an endosomal acidification inhibitor (chloroquine), a TLR9 antagonist inhibitory CpG DNA, or overexpression of a dominant negative (DN) form of MyD88. In contrast, overexpression of DN-IRAK1 or DN-TRAF6 only partially inhibited CpG DNA-induced Cox-2 promoter activity and NF-κB activation, indicating the presence of additional signaling modulators down-stream of MyD88. CpG DNA-induced Cox-2 promoter activity was substantially suppressed in cells overexpressing super-suppressive IκB (IκB-arachidonic acid), DN-p38, or DN-CREB. In addition, Cox-2 promoter-luciferase reporters with alterations in predicted cis-acting transcriptional regulatory elements revealed that C/EBP, Ets-1, NF-κB, and CREB-binding sites are essential for optimal Cox-2 expression in response to CpG DNA. Conclusively, these results demonstrate that endosomal DNA processing and TLR9/MyD88-dependent activation of NF-κB and p38 are required for transcriptional regulation of Cox-2 expression induced by CpG DNA, and suggest that interleukin-1 receptor-associated kinase and/or TRAF6 may be a diverging point for NF-κB activation in response to CpG DNA in RAW264.7 cells.

Original languageEnglish (US)
Pages (from-to)22563-22573
Number of pages11
JournalJournal of Biological Chemistry
Volume278
Issue number25
DOIs
StatePublished - Jun 20 2003

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Myeloid Differentiation Factor 88
Cyclooxygenase 2
DNA
TNF Receptor-Associated Factor 6
Chemical activation
Interleukin-1 Receptor-Associated Kinases
Transcriptional Regulatory Elements
Acidification
Macrophages
Chloroquine
Luciferases
Arachidonic Acid
Gene expression
Modulators
Transcription Factors

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Myeloid differentiation factor 88-dependent transcriptional regulation of cyclooxygenase-2 expression by CpG DNA : Role of NF-κB and p38. / Yeo, Seon Ju; Gravis, Demetrius; Yoon, Jae Geun; Yi, Ae-Kyung.

In: Journal of Biological Chemistry, Vol. 278, No. 25, 20.06.2003, p. 22563-22573.

Research output: Contribution to journalArticle

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