title: Roles of mPGES-1, an inducible prostaglandin E synthase, in enhancement of LPS-induced lymphangiogenesis in a mouse peritonitis model.
abstract: OBJECTIVE
  Lymphangiogenesis is frequently observed during inflammation, and this inflammation-induced lymphangiogenesis (IL) is a phenomenon actively involved in the pathophysiology of inflammation. We explored the roles of an inducible prostaglandin E synthase, mPGES-1, in IL elicited by lipopolysaccharide (LPS).
  
  
  METHODS
  Peritonitis was induced in mice by intraperitoneal injection of LPS (E. coli 0111-B4; 25μg/mouse every 2days), and IL was evaluated by LYVE-1 immunostaining of whole-mount diaphragm tissues.
  
  
  RESULTS
  Compared to vehicle-treated wild-type (WT) mice, lymphatics in the diaphragms of mice injected with LPS were widened and the number of LYVE-1-positive ladder-structured lymphatics increased temporally. This increase in lymphangiogenesis was accompanied by increased expression of vascular endothelial growth factor (VEGF)-C/D in the diaphragms. In mice treated with celecoxib, a cyclooxygenase-2 inhibitor, IL was suppressed with reduced expression of VEGF-C/D. This was also observed in mPGES-1 knockout mice (KO). Immunoreactive COX-2 and mPGES-1 were detected in both CD11b-positive and CD3ε-positivecells in the diaphragm. When FITC-dextran was injected into the peritoneal cavities, the amount of residual FITC-dextran was reduced significantly in WT mice injected with LPS, and this reduction was significantly decreased in mPGES-1 KO mice.
  
  
  CONCLUSIONS
  The present results suggest that mPGES-1 plays a significant role in lymphangiogenesis during inflammation, and represents a novel target for controlling IL.
authors.affiliation: Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan; Department of Anesthesiology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan; Department of Molecular Pharmacology, Graduate School of Medical Sciences, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Matsuda
authors.affiliation: Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan; Department of Molecular Pharmacology, Graduate School of Medical Sciences, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Hosono
authors.affiliation: Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan; Department of Anesthesiology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan; Department of Molecular Pharmacology, Graduate School of Medical Sciences, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Seri
authors.initials: S
authors.lastname: Tsuru
authors.affiliation: Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan; Department of Anesthesiology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan; Department of Molecular Pharmacology, Graduate School of Medical Sciences, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Kurashige
authors.affiliation: Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan; Department of Molecular Pharmacology, Graduate School of Medical Sciences, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sekiguchi
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.affiliation: International Research and Development Center for Mucosal Vaccine, Institute of Medical Science, Shirokanedai, Tokyo 108-8639, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uematsu
authors.affiliation: Department of Anesthesiology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan; Department of Molecular Pharmacology, Graduate School of Medical Sciences, Sagamihara, Kanagawa 252-0374, Japan. Electronic address: mmajima@med.kitasato-u.ac.jp.
authors.forename: Masataka
authors.initials: M
authors.lastname: Majima
mesh_terms: D000818:Animals; D000068579:Celecoxib / Q000494:pharmacology; D003964:Diaphragm / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D042583:Lymphangiogenesis / Q000187:drug effects* / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D010538:Peritonitis / Q000139:chemically induced* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000071876:Prostaglandin-E Synthases; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism
chemical_list: D000068579:Celecoxib; D006023:Glycoproteins; D019746:Intramolecular Oxidoreductases; D008070:Lipopolysaccharides; D026901:Membrane Transport Proteins; D000071876:Prostaglandin-E Synthases; D042582:Vascular Endothelial Growth Factor C; C492273:LYVE1 protein, mouse; C440499:lipopolysaccharide, Escherichia coli O111 B4; C467483:vascular endothelial growth factor C, mouse; C000605865:Ptges protein, mouse
keywords: Cyclooxygenase-2; Inflammation; Lymphangiogenesis; Peritonitis; Prostaglandin; Synthase; mPGES-1