title: Lipoxin A4 attenuation of endothelial inflammation response mimicking pancreatitis-induced lung injury.
abstract: Lipoxins (LXs) and their analogues are known to display potent anti-inflammatory actions. Previously, we reported that lipoxin A4 (LXA4) possessed powerful anti-inflammatory properties in acute pancreatitis in rats and that it may ameliorate the concomitant acute lung injury by reducing cytokine generation and inhibiting neutrophil activation. Considering that the vascular endothelium plays an important role during adherence, migration and activation of leukocytes, the present study was designed to investigate the effects of LXA4 on the inflammatory response induced by tumor necrosis factor α (TNF-α) in human pulmonary microvascular endothelial cells (HPMECs) and explore the potential mechanisms involved in these processes. We found that LXA4 markedly down-regulated the expression of monocyte chemotactic protein-1 (MCP-1), E-selectin, and interleukin-6 (IL-6) mRNA, as well as intercellular adhesion molecule-1 (ICAM-1) in TNF-α-exposed HPMECs. Moreover, LXA4 inhibited the phosphorylation and nuclear translocation of nuclear factor-κB/p65 (NF-κB/p65) and phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) in HPMECs following TNF-α stimulation. Heme oxygenase-1 (HO-1), a cytoprotective enzyme, was up-regulated by LXA4 in both non- and TNF-α-stimulated HPMECs. In conclusion, the protective effects of LXA4 to ALI may be executed through inhibition inflammation pathways of NF-κB and p38 MAPK and up-regulation of cytoprotective HO-1.
authors.affiliation: Department of Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou 325000, Zhejiang Province, China.
authors.forename: Wanzhi
authors.initials: W
authors.lastname: Lv
authors.forename: Chongqing
authors.initials: C
authors.lastname: Lv
authors.forename: Suhui
authors.initials: S
authors.lastname: Yu
authors.forename: Yunxiu
authors.initials: Y
authors.lastname: Yang
authors.forename: Hongru
authors.initials: H
authors.lastname: Kong
authors.forename: Jianming
authors.initials: J
authors.lastname: Xie
authors.forename: Hongwei
authors.initials: H
authors.lastname: Sun
authors.forename: Roland
authors.initials: R
authors.lastname: Andersson
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.forename: Bicheng
authors.initials: B
authors.lastname: Chen
authors.forename: Mengtao
authors.initials: M
authors.lastname: Zhou
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015153:Blotting, Western; D002478:Cells, Cultured; D054412:Chemokine CCL8 / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D044045:Lipoxins / Q000627:therapeutic use*; D008168:Lung / Q000098:blood supply / Q000166:cytology / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D010195:Pancreatitis / Q000150:complications*; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019892:eIF-2 Kinase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D054412:Chemokine CCL8; D019040:E-Selectin; D015850:Interleukin-6; D044045:Lipoxins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C040527:lipoxin A4; D018799:Intercellular Adhesion Molecule-1; D019892:eIF-2 Kinase; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Human pulmonary microvascular endothelial cells; inflammation; lipoxin A4; nuclear factor-κB; tumor necrosis factor α