title: Overexpression of uncoupling protein 2 in THP1 monocytes inhibits beta2 integrin-mediated firm adhesion and transendothelial migration.
abstract: OBJECTIVE
  Uncoupling protein 2 (UCP2) belongs to the mitochondrial anion carrier family and regulates production of reactive oxygen species in macrophages. Previous studies have shown that selective genetic disruption of UCP2 in bone marrow cells results in excess accumulation of monocytes/macrophages in the vascular wall of hypercholesterolemic low-density lipoprotein receptor-deficient (LDLR-/-) mice. Here we investigated whether UCP2 regulates expression of genes involved in monocyte recruitment.
  
  
  RESULTS
  UCP2 overexpression in THP1 monocytes, which induced a 10-fold increase in mitochondrial UCP2 protein levels, reduced steady-state level of intracellular reactive oxygen species (ROS) and H2O2-induced ROS production. THP1 monocytes with UCP2 overexpression showed lower intracellular calcium levels and less H2O2-triggered intracellular calcium mobilization, and less protein and mRNA levels of beta2 integrins, most notably CD11b. UCP2 overexpression reduced beta2 integrin-mediated firm adhesion of monocytes to either tumor necrosis factor-alpha (TNF-alpha)-stimulated human aortic endothelial cell (HAEC) monolayers or to plates coated with intercellular adhesion molecule-1, not vascular cell adhesion molecule-1. UCP2 overexpression also inhibited cell spreading and actin polymerization in monocytes treated with TNF-alpha and monocyte chemoattractant protein-1 (MCP-1), and reduced MCP-1-induced transmigration of monocytes through HAEC monolayers.
  
  
  CONCLUSIONS
  Mitochondrial UCP2 in circulating monocytes may prevent excessive accumulation of monocytes/macrophages in the arterial wall, thereby reducing atherosclerotic plaque formation.
authors.affiliation: Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Je-Won
authors.initials: JW
authors.lastname: Ryu
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Hong
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Maeng
authors.forename: Jae-Bum
authors.initials: JB
authors.lastname: Kim
authors.forename: Jesang
authors.initials: J
authors.lastname: Ko
authors.forename: Joong Yeol
authors.initials: JY
authors.lastname: Park
authors.forename: Ki-Up
authors.initials: KU
authors.lastname: Lee
authors.forename: Myeong Ki
authors.initials: MK
authors.lastname: Hong
authors.forename: Seong Wook
authors.initials: SW
authors.lastname: Park
authors.forename: You Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Ki Hoon
authors.initials: KH
authors.lastname: Han
mesh_terms: D000199:Actins / Q000378:metabolism; D001011:Aorta / Q000166:cytology; D001161:Arteriosclerosis / Q000378:metabolism; D001704:Biopolymers; D018821:CD18 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020013:Calcium Signaling; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D002460:Cell Line / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2 / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology; D015870:Gene Expression; D006801:Humans; D007473:Ion Channels; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000502:physiology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000071246:Uncoupling Protein 2
chemical_list: D000199:Actins; D001704:Biopolymers; C515334:CCR2 protein, human; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C000604389:UCP2 protein, human; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2