The Phosphatidylinositol 3-Kinase-Akt Pathway Limits Lipopolysaccharide Activation of Signaling Pathways and Expression of Inflammatory Mediators in Human Monocytic Cells

摘要: Monocytes and macrophages express cytokines procoagulant molecules in various inflammatory diseases. In sepsis, lipopolysaccharide (LPS) from Gram-negative bacteria induces tumor necrosis factor-alpha (TNF-alpha) tissue factor (TF) monocytic cells via the activation of transcription factors Egr-1, AP-1, nuclear factor-kappa B. However, signaling pathways that negatively regulate LPS-induced TNF-alpha TF expression are currently unknown. We report inhibition phosphatidylinositol 3-kinase (PI3K)-Akt pathway enhances mitogen-activated protein kinase (ERK1/2, p38, JNK) downstream targets AP-1 Egr-1. addition, PI3K-Akt enhanced translocation B prevented Akt-dependent inactivation glycogen synthase kinase-beta, which increased transactivational activity p65. propose human monocytes limits LPS induction expression. Our study provides new insight into inhibitory mechanism by ensures transient these potent mediators.