Endotoxin에 의해 유도되는 tissue factor 및 plasminogen activator inhibitor-1 유전자의 발현조절에 관한 연구

Abstract

The effects of protein kinase inhibitors on the expression of tissue factor and plasminogen activator inhibitor-1 (PAI-1) genes was investigated in U937 human monocyte cell line using reverse transcriptase polymerase chain reaction (RT-PCR). Treatment of U937 cells with PD98059, extracellular signal-regulated protein kinase 1/2 (ERK1/2) pathway inhibitor, for 8 hrs decreased LPS-induced production of both tissue factor and PAI-1 mRNA. PD98059 also inhibited NF-kB and AP-1 which are important in the gene expression of tissue factor and PAI-1, respectively. Inhibition of LPS-induced expression of tissue factor and PAI-1 by SB203580, p38 MAPK inhibitor, was less than the inhibition by PD98059. Collectively, the experiments indicate that ERK1/2 pathways positively regulate tissue factor and PAI-1 gene expression through the activation of NF-kB and AP-1. Due to the critical role that tissue factor and PAI-1 play in mediating microthrombosis induced by endotoxin, the inhibitory effects of PD98059 on the gene expression suggest that ERK1/2 pathway may be a target to prevent endotoxin-induced thrombosis.