title: Interleukin-25 induces pulmonary arterial remodeling via natural killer T cell-dependent mechanisms.
abstract: BACKGROUND
  Recent studies have shown that prolonged Th2-type immune inflammation in the lung induces pulmonary arterial remodeling, in part through the induction of resistin-like molecule α (RELMα) expression. However, the role of interleukin-25 (IL-25; which promotes this inflammation) in the development of the pulmonary arterial remodeling remains unknown.
  
  
  METHODS
  Ovalbumin (OVA)-sensitized C57BL/6 mice were challenged with OVA inhalation 3 times a week for 3 weeks. The effects of neutralizing anti-IL-25 antibody on OVA-induced pulmonary arterial remodeling and RELMα expression in the lung were examined. The pulmonary arterial remodeling and RELMα expression in the lung were examined in lung-specific IL-25 transgenic mice (CC10 IL-25 mice) and CC10 IL-25 mice in a natural killer T (NKT) cell-deficient background (CC10 IL-25 NKT(-/-) mice).
  
  
  RESULTS
  Repeated OVA inhalation induced pulmonary arterial wall thickening and the expression of IL-25 and RELMα mRNA in the lung in OVA-sensitized mice. Injection of neutralizing anti-IL-25 antibody inhibited OVA-induced pulmonary arterial wall thickening and RELMα expression in the lung. CC10 IL-25 mice, but not CC10 IL-25 NKT(-/-) mice, spontaneously developed pulmonary arterial wall thickening and RELMα expression in the lung at 6 months of age.
  
  
  CONCLUSIONS
  Prolonged expression of IL-25 in the lung induces pulmonary arterial wall thickening by NKT cell-dependent mechanisms.
authors.affiliation: Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Kawashima
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirose
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tamachi
authors.forename: Kei
authors.initials: K
authors.lastname: Ikeda
authors.forename: Koji
authors.initials: K
authors.lastname: Tokoyoda
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D005260:Female; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D011651:Pulmonary Artery / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D014598:Uteroglobin / Q000235:genetics / Q000276:immunology
chemical_list: D000941:Antigens; D020381:Interleukin-17; C556390:Scgb1a1 protein, mouse; D010047:Ovalbumin; D014598:Uteroglobin