title: Inhibition of angiogenesis by IL-32: possible role in asthma.
abstract: BACKGROUND
  IL-32 is a proinflammatory cytokine involved in various chronic inflammatory diseases. Chronic airway inflammation in asthmatic patients results in structural airway changes, including angiogenesis. Vascular endothelial growth factor (VEGF) is a key inducer of angiogenesis in the airways of asthmatic patients.
  
  
  OBJECTIVE
  The aim of the study was to investigate the expression and function of IL-32 in patients with angiogenesis and asthma.
  
  
  METHODS
  The expression and regulation of IL-32 in normal human bronchial epithelial (NHBE) cells was analyzed by using RT-PCR, ELISA, Western blotting, immunofluorescent staining, and flow cytometry. After knockdown of IL-32 in NHBE cells by small interfering RNA (siRNA) transfections, VEGF secretion was quantified by means of ELISA. New blood vessel formation was determined with human umbilical vein endothelial cells by culturing with supernatants from IL-32 siRNA-transfected NHBE cells. IL-32 was determined in serum and induced sputum samples of asthmatic patients and healthy control subjects by means of ELISA.
  
  
  RESULTS
  IL-32 is expressed in NHBE cells on stimulation with IFN-γ, TNF-α, T(H)1 cells, and rhinovirus. Inhibition of IL-32 expression resulted in significantly increased secretion of the proangiogenic factors VEGF and platelet-derived growth factor by NHBE cells. Human umbilical vein endothelial cells cultured in supernatants from IL-32 siRNA-transfected NHBE cells showed enhanced in vitro angiogenesis. IL-32 is detectable in induced sputum from asthmatic patients. IL-32 serum levels were significantly higher in asthmatic patients compared with those seen in healthy control subjects and correlated with response to asthma treatment.
  
  
  CONCLUSIONS
  IL-32 is induced by IFN-γ, TNF-α, T(H)1 cells, and rhinovirus in bronchial epithelial cells. It inhibits angiogenesis, and its serum levels are associated with a good treatment response in asthmatic patients.
authors.affiliation: Swiss Institute of Allergy and Asthma Research, Davos, Switzerland. norbert.meyer@siaf.uzh.ch
authors.forename: Norbert
authors.initials: N
authors.lastname: Meyer
authors.forename: Janine
authors.initials: J
authors.lastname: Christoph
authors.forename: Heidi
authors.initials: H
authors.lastname: Makrinioti
authors.forename: Philippe
authors.initials: P
authors.lastname: Indermitte
authors.forename: Claudio
authors.initials: C
authors.lastname: Rhyner
authors.forename: Michael
authors.initials: M
authors.lastname: Soyka
authors.forename: Thomas
authors.initials: T
authors.lastname: Eiwegger
authors.forename: Maciej
authors.initials: M
authors.lastname: Chalubinski
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wanke
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujita
authors.forename: Paulina
authors.initials: P
authors.lastname: Wawrzyniak
authors.forename: Simone
authors.initials: S
authors.lastname: Bürgler
authors.forename: Sherrie
authors.initials: S
authors.lastname: Zhang
authors.forename: Mübeccel
authors.initials: M
authors.lastname: Akdis
authors.forename: Günter
authors.initials: G
authors.lastname: Menz
authors.forename: Cezmi
authors.initials: C
authors.lastname: Akdis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D001980:Bronchi / Q000098:blood supply*; D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D010850:Picornaviridae Infections / Q000276:immunology / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D018927:Anti-Asthmatic Agents; C496971:IL32 protein, human; D007378:Interleukins; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D007371:Interferon-gamma