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

作者：Thapa Bikash; Kim Yeon Hyang; Kwon Hyung Joo; Kim Doo Sik^*

来源：Molecular Immunology, 2012, 49(4): 572-581.

DOI：10.1016/j.molimm.2011.10.004

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

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-kappa B 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.

• 出版日期2012-1