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Neurotrophins (NTs) such as brain\u2010derived neurotrophic factor (BDNF), well\u2010known in the nervous system, can regulate Ca<jats:sup>2+<\/jats:sup> signalling, and interact with cytokines in contributing to airway hyperreactivity. In this study, we determined whether and how BDNF regulates human ASM cell proliferation in the presence of inflammation, thus testing its potential role in airway remodelling. Cells were treated with 10 nM BDNF, 25 ng\/ml tumour necrosis factor (TNF\u2010\u03b1) or interleukin\u201013 (IL\u201013), or 10 ng\/ml platelet\u2010derived growth factor (PDGF). Proliferation was measured using CyQuant dye, with immunoblotting of cell cycle proteins predicted to change with proliferation. Forty\u2010eight hours of BDNF enhanced ASM proliferation to \u223c50% of that by PDGF or cytokines. Transfection with small interfering RNAs (siRNAs) targeting high\u2010affinity tropomyosin\u2010related kinase B receptor abolished BDNF effects on proliferation, whereas low\u2010affinity 75 kD neurotrophin receptor (p75NTR) siRNA had no effect. Systematic pharmacologic inhibition of different components of ERK1\/2 and PI3K\/Akt1 pathways blunted BDNF or TNF\u2010\u03b1\u2013induced proliferation. BDNF also induced I\u03baB phosphorylation and nuclear translocation of p50 and p65 NF\u2010\u03baB subunits, with electron mobility shift assay confirmation of NF\u2010\u03baB binding to consensus DNA sequence. These results demonstrate that NTs such as BDNF can enhance human ASM cell proliferation by activating proliferation\u2010specific signalling pathways and a versatile transcription factor such as NF\u2010\u03baB, which are common to cytokines and growth factors involved in asthma.<\/jats:p>","DOI":"10.1111\/j.1582-4934.2011.01356.x","type":"journal-article","created":{"date-parts":[[2011,6,9]],"date-time":"2011-06-09T05:14:19Z","timestamp":1307596459000},"page":"812-823","source":"Crossref","is-referenced-by-count":79,"title":["Brain\u2010derived neurotrophic factor induces proliferation of human airway smooth muscle cells"],"prefix":"10.1111","volume":"16","author":[{"given":"Bharathi","family":"Aravamudan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Pabelick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. 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