title: Differential regulation of neurotrophin expression in human bronchial smooth muscle cells.
abstract: BACKGROUND
  Human bronchial smooth muscle cells (HBSMC) may regulate airway inflammation by secreting cytokines, chemokines and growth factors. The neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), have been shown to be elevated during airway inflammation and evoke airway hyperresponsiveness. We studied if HBSMC may be a source of NGF, BDNF and NT-3, and if so, how inflammatory cytokines may influence their production.
  
  
  METHODS
  Basal and cytokine (IL-1beta, IFN-gamma, IL-4)-stimulated neurotrophin expression in HBSMC cultured in vitro was quantified. The mRNA expression was quantified by real-time RT-PCR and the protein secretion into the cell culture medium by ELISA.
  
  
  RESULTS
  We observed a constitutive NGF, BDNF and NT-3 expression. IL-1beta stimulated a transient increase of NGF, while the increase of BDNF had a later onset and was more sustained. COX-inhibitors (indomethacin and NS-398) markedly decreased IL-1beta-stimulated secretion of BDNF, but not IL-1beta-stimulated NGF secretion. IFN-gamma increased NGF expression, down-regulated BDNF expression and synergistically enhanced IL-1beta-stimulated NGF expression. In contrast, IL-4 had no effect on basal NGF and BDNF expression, but decreased IL-1beta-stimulated NGF expression. NT-3 was not altered by the tested cytokines.
  
  
  CONCLUSIONS
  Taken together, our data indicate that, in addition to the contractile capacity, HBSMC can express NGF, BDNF and NT-3. The expression of these neurotrophins may be differently regulated by inflammatory cytokines, suggesting a dynamic interplay that might have a potential role in airway inflammation.
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden. Cecilia.Kemi@ki.se
authors.forename: Cecilia
authors.initials: C
authors.lastname: Kemi
authors.forename: Johan
authors.initials: J
authors.lastname: Grunewald
authors.forename: Anders
authors.initials: A
authors.lastname: Eklund
authors.forename: Caroline Olgart
authors.initials: CO
authors.lastname: Höglund
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004338:Drug Combinations; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D007375:Interleukin-1; D020933:Neurotrophin 3; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma; D020932:Nerve Growth Factor