title: Unfractionated heparin attenuates LPS-induced IL-8 secretion via PI3K/Akt/NF-κB signaling pathway in human endothelial cells.
abstract: Unfractionated heparin (UFH) is largely used as anti-thrombotic drug. While UFH has been shown to suppress lipopolysaccharide (LPS)-induced nuclear factor-κB (NF-κB) activation, intracellular upstream events that cause NF-κB down-regulation in response to UFH remain unclear. Thus, we investigated the involvement of phosphoinositide-3-OH kinase (PI3K)/Akt in the inhibition of LPS-activated NF-κB pathway by UFH in human pulmonary microvascular endothelial cells (HPMECs). Pretreatment with UFH (0.1-1U/ml) significantly inhibited LPS (10μg/ml)-stimulated interleukin (IL)-6 and IL-8 production in HPMECs. LPS activated Akt and NF-κB, whereas UFH suppresses LPS-induced Akt phosphorylation and NF-κB nuclear translocation, which were required for IL-6 and IL-8 gene transcription. Inhibition studies by using wortmannin abrogated NF-κB-mediated IL-6 and IL-8 expression, suggesting the requirement of PI3K/Akt pathway. Our data provided the first evidence that UFH might repress LPS-activated PI3K/Akt pathway, leading to inhibitory effect of NF-κB activation with diminished IL-6 and IL-8 expression in HPMECs.
authors.affiliation: Department of Intensive Care Unit, The First Affiliated Hospital, China Medical University, Bei-er Road 92, Shenyang 110001, Liaoning Province, PR China. Electronic address: vincentzh002@outlook.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Intensive Care Unit, The First Affiliated Hospital, China Medical University, Bei-er Road 92, Shenyang 110001, Liaoning Province, PR China.
authors.forename: Yina
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Intensive Care Unit, The First Affiliated Hospital, China Medical University, Bei-er Road 92, Shenyang 110001, Liaoning Province, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Intensive Care Unit, The First Affiliated Hospital, China Medical University, Bei-er Road 92, Shenyang 110001, Liaoning Province, PR China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Intensive Care Unit, The First Affiliated Hospital, China Medical University, Bei-er Road 92, Shenyang 110001, Liaoning Province, PR China. Electronic address: lx2008yy@gmail.com.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Ma
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000276:immunology*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism*; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D006493:Heparin; D051550:I-kappa B Kinase; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin; C508606:CXCL8 protein, human; C508600:IL6 protein, human; C496560:IKBKB protein, human
keywords: Endothelial cells; Lipopolysaccharide; Nuclear factor-κB; Phosphoinositide-3-kinase; Unfractionated heparin