title: Modulation of lung inflammation by vessel dilator in a mouse model of allergic asthma.
abstract: BACKGROUND
  Atrial natriuretic peptide (ANP) and its receptor, NPRA, have been extensively studied in terms of cardiovascular effects. We have found that the ANP-NPRA signaling pathway is also involved in airway allergic inflammation and asthma. ANP, a C-terminal peptide (amino acid 99-126) of pro-atrial natriuretic factor (proANF) and a recombinant peptide, NP73-102 (amino acid 73-102 of proANF) have been reported to induce bronchoprotective effects in a mouse model of allergic asthma. In this report, we evaluated the effects of vessel dilator (VD), another N-terminal natriuretic peptide covering amino acids 31-67 of proANF, on acute lung inflammation in a mouse model of allergic asthma.
  
  
  METHODS
  A549 cells were transfected with pVD or the pVAX1 control plasmid and cells were collected 24 hrs after transfection to analyze the effect of VD on inactivation of the extracellular-signal regulated receptor kinase (ERK1/2) through western blot. Luciferase assay, western blot and RT-PCR were also performed to analyze the effect of VD on NPRA expression. For determination of VD's attenuation of lung inflammation, BALB/c mice were sensitized and challenged with ovalbumin and then treated intranasally with chitosan nanoparticles containing pVD. Parameters of airway inflammation, such as airway hyperreactivity, proinflammatory cytokine levels, eosinophil recruitment and lung histopathology were compared with control mice receiving nanoparticles containing pVAX1 control plasmid.
  
  
  RESULTS
  pVD nanoparticles inactivated ERK1/2 and downregulated NPRA expression in vitro, and intranasal treatment with pVD nanoparticles protected mice from airway inflammation.
  
  
  CONCLUSIONS
  VD's modulation of airway inflammation may result from its inactivation of ERK1/2 and downregulation of NPRA expression. Chitosan nanoparticles containing pVD may be therapeutically effective in preventing allergic airway inflammation.
authors.affiliation: Division of Allergy and Immunology, University of South Florida, Tampa, FL 33612, USA. xwang1@health.usf.edu
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Wang
authors.forename: Weidong
authors.initials: W
authors.lastname: Xu
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Kong
authors.forename: Dongqing
authors.initials: D
authors.lastname: Chen
authors.forename: Gary
authors.initials: G
authors.lastname: Hellermann
authors.forename: Terry A
authors.initials: TA
authors.lastname: Ahlert
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Giaimo
authors.forename: Stephania A
authors.initials: SA
authors.lastname: Cormier
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.forename: Richard F
authors.initials: RF
authors.lastname: Lockey
authors.forename: Subhra
authors.initials: S
authors.lastname: Mohapatra
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Mohapatra
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D016085:Bronchoconstrictor Agents; D002460:Cell Line; D048271:Chitosan; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006801:Humans; D008156:Luciferases / Q000737:chemistry; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology; D011014:Pneumonia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000502:physiology; D012130:Respiratory Hypersensitivity / Q000150:complications* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000378:metabolism; D014162:Transfection
chemical_list: D016085:Bronchoconstrictor Agents; D016207:Cytokines; D010446:Peptide Fragments; C054548:atrial natriuretic factor prohormone (31-67); D016210:Methacholine Chloride; D009320:Atrial Natriuretic Factor; D010047:Ovalbumin; D048271:Chitosan; D008156:Luciferases; D048049:Extracellular Signal-Regulated MAP Kinases; D017461:Receptors, Atrial Natriuretic Factor