Effects of neurotrophins on human bronchial smooth muscle cell migration and matrix metalloproteinase-9 secretion.
The neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) have been found to be upregulated in inflammatory pulmonary diseases, including asthma. The functional role for the neurotrophins in the airways is still not known, but it has been proposed that neurotrophins induce airway hyperreactivity and tissue remodeling. Bronchial smooth muscle cells have been suggested to be involved in the remodeling process through their capacity to proliferate, migrate, and secrete inflammatory mediators and matrix metalloproteinases (MMPs). Therefore, we studied the effect of NGF, BDNF, and NT-3 on human bronchial smooth muscle cell (HBSMC) migration and MMP-2 and MMP-9 secretion. Immunocytochemistry studies showed that HBSMCs expressed the neurotrophin receptors TrkA, TrkB, and TrkC. BDNF, NT-3, and NGF increased MMP-9, but not MMP-2, secretion as shown by zymography. BDNF and NT-3, but not NGF, stimulated HBSMC migration as evaluated by Boyden chamber. Taken together, our data indicate that the neurotrophins may stimulate events important for airway remodeling.
Dagnell
Charlotta
C
Department of Medicine Solna, Division of Respiratory Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Kemi
Cecilia
C
Klominek
Julius
J
Eriksson
Per
P
Sköld
C Magnus
CM
Eklund
Anders
A
Grunewald
Johan
J
Olgart Höglund
Caroline
C
D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D020933:Neurotrophin 3 / Q000494:pharmacology; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor; D020780:Matrix Metalloproteinase 9