Differential regulation of neurotrophin expression in human bronchial smooth muscle cells.
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.
Kemi
Cecilia
C
Division of Respiratory Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden. Cecilia.Kemi@ki.se
Grunewald
Johan
J
Eklund
Anders
A
Höglund
Caroline Olgart
CO
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
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