Novel regulatory mechanism and functional implication of plasminogen activator inhibitor-1 (PAI-1) expression in CpG-ODN-stimulated macrophages

Bikash Thapa, Yeon Hyang Kim, Hyung Joo Kwon, Doo Sik Kim

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Macrophages are activated by recognizing bacterial DNA and CpG-oligodeoxynucleotides (CpG-ODNs) through Toll-like receptor-9 (TLR-9). Plasminogen activator inhibitor-1 (PAI-1) has been shown to be an important factor in inflammation-induced macrophage migration which is essential for defense functions. The aim of this study was to demonstrate the molecular mechanism associated with the regulation of PAI-1 expression and its biological significance in CpG-ODN-stimulated mouse macrophages. Our results clearly show that PAI-1 expression in macrophages was highly up-regulated by CpG-ODN-stimulation in vitro and in vivo. The TLR-9-mediated stimulation of PAI-1 expression was independent of the NF-κB pathway and involved the synergistic activation of Sp1 and Elk-1 by the MEK1/2-ERK and JNK signaling pathways. The elevated PAI-1 expression resulted in significantly enhanced transmigration of RAW264.7 cells through vitronectin but not through fibronectin. We suggest that CpG-ODN plays a role in regulating macrophage migration by stimulating the expression of PAI-1, and the migration is modulated depending on the microenvironmental extracellular matrix components.

Original languageEnglish
Pages (from-to)572-581
Number of pages10
JournalMolecular Immunology
Volume49
Issue number4
DOIs
StatePublished - Jan 2012
Externally publishedYes

Keywords

  • CpG-ODN
  • Macrophage
  • Migration
  • PAI-1
  • TLR-9
  • Vitronectin

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