Reference - Detail
|Author||Thapa B, Kim YH, Kwon HJ, Kim DS.|
|Title||Novel regulatory mechanism and functional implication of plasminogen activator inhibitor-1 (PAI-1) expression in CpG-ODN-stimulated macrophages.|
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.
|MeSH||Animals Cell Line Cell Movement / genetics Cellular Microenvironment Extracellular Matrix / genetics Extracellular Matrix / metabolism Extracellular Signal-Regulated MAP Kinases / metabolism Fibronectins / metabolism MAP Kinase Kinase 1 / metabolism MAP Kinase Kinase 2 / metabolism MAP Kinase Signaling System / genetics Macrophages / cytology Macrophages / drug effects* Macrophages / metabolism Male Mice Mice, Inbred BALB C Mice, Knockout NF-kappa B / metabolism Oligodeoxyribonucleotides / genetics Oligodeoxyribonucleotides / metabolism Oligodeoxyribonucleotides / pharmacology* Promoter Regions, Genetic Protein Kinases / metabolism Serpin E2 / biosynthesis* Serpin E2 / genetics Serpin E2 / metabolism Toll-Like Receptor 9 / metabolism Up-Regulation Vitronectin / metabolism ets-Domain Protein Elk-1 / metabolism|
|WOS Category||IMMUNOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY|
|DNA material||MSM Mouse BAC (RDB04214) MSMg01-392H15|