title: Neurokinin-1 receptor, a new modulator of lymphangiogenesis in obese-asthma phenotype.
abstract: OBJECTIVE
  Obesity and asthma are widely prevalent and associated disorders. Recent studies of our group revealed that Substance P (SP) is involved in pathophysiology of obese-asthma phenotype in mice through its selective NK1 receptor (NK1-R). Lymphangiogenesis is impaired in asthma and obesity, and SP activates contractile and inflammatory pathways in lymphatics. Our aim was to study whether NK1-R expression was involved in lymphangiogenesis on visceral (VAT) and subcutaneous (SAT) adipose tissues and in the lungs, in obese-allergen sensitized mice.
  
  
  METHODS
  Diet-induced obese and ovalbumin (OVA)-sensitized Balb/c mice were treated with a selective NK1-R antagonist (CJ 12,255, Pfizer Inc., USA) or placebo. Lymphatic structures (LYVE-1+) and NK1-R expression were analyzed by immunohistochemistry. A semi-quantitative score methodology was used for NK1-R expression.
  
  
  RESULTS
  Obesity and allergen-sensitization together increased the number of LYVE-1+ lymphatics in VAT and decreased it in SAT and lungs. NK1-R was mainly expressed on adipocyte membranes of VAT, blood vessel areas of SAT, and in lung epithelium. Obesity and allergen-sensitization combined increased the expression of NK1-R in VAT, SAT and lungs. NK1-R antagonist treatment reversed the effects observed in lymphangiogenesis in those tissues.
  
  
  CONCLUSIONS
  The obese-asthma phenotype in mice is accompanied by increased expression of NK1-R on adipose tissues and lung epithelium, reflecting that SP released during inflammation may act directly on these tissues. Blocking NK1-R affects lymphangiogenesis, implying a role of SP, with opposite physiological consequences in VAT, and in SAT and lungs. Our results provide a clue for a novel SP role in the obese-asthma phenotype.
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Porto, Portugal. renata.cg.ramalho@gmail.com
authors.forename: Renata
authors.initials: R
authors.lastname: Ramalho
authors.forename: Joana
authors.initials: J
authors.lastname: Almeida
authors.forename: Rubén
authors.initials: R
authors.lastname: Fernandes
authors.forename: Raquel
authors.initials: R
authors.lastname: Costa
authors.forename: Ana
authors.initials: A
authors.lastname: Pirraco
authors.forename: Luísa
authors.initials: L
authors.lastname: Guardão
authors.forename: Luís
authors.initials: L
authors.lastname: Delgado
authors.forename: André
authors.initials: A
authors.lastname: Moreira
authors.forename: Raquel
authors.initials: R
authors.lastname: Soares
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D050152:Intra-Abdominal Fat / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D042601:Lymphatic Vessels / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D018040:Receptors, Neurokinin-1 / Q000096:biosynthesis*; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D050507:Subcutaneous Fat, Abdominal / Q000378:metabolism / Q000473:pathology
chemical_list: D018040:Receptors, Neurokinin-1
keywords: Allergen-challenge; Asthma; LYVE-1; Lymphangiogenesis; NK1-R; Obesity; Substance P