Selective induction of nerve growth factor and brain-derived neurotrophic factor by LPS and allergen in dendritic cells.
BACKGROUND
Neurotrophins are produced by various cells upon different stimuli and participate in the initiation and regulation of inflammation in various diseases including allergy and asthma, but little is known about the production and control of neurotrophins by dendritic cells (DCs). The aim of this study was to assess whether DCs produce the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), and whether inflammatory stimuli or allergens are able to induce the production of neurotrophic factors.


METHODS
Monocyte-derived dendritic cells (MoDCs) were generated from different donors. The neurotrophins NGF and BDNF were demonstrated by RT-PCR, Western blotting, flow cytometry analysis and fluorescence microscopy. MoDCs were cultured and stimulated with lipopolysaccharide (LPS) or allergen for 24 h. The supernatants and cells were collected. Measurement for NGF and BDNF was performed by ELISA.


RESULTS
DCs express mRNA for the neurotrophins NGF and BDNF. Proteins were detectable by Western blot, FACS analysis and fluorescence microscopy. LPS led to an up-regulation of BDNF, while NGF was unaffected. Cell lysates demonstrated an increased amount of BDNF after stimulation with LPS or allergen, while NGF was not affected significantly.


CONCLUSIONS
DCs are a source of neurotrophins. LPS selectively regulates the production of BDNF. Allergen stimulation leads to an LPS-independent regulation. This contributes to a complex involvement of neurotrophins in allergic diseases.
Noga
O
O
Department of Infectious and Respiratory Diseases, Charité, University Medicine, Berlin, Germany. oliver.noga@charite.de
Peiser
M
M
Altenähr
M
M
Schmeck
B
B
Wanner
R
R
Dinh
Q T
QT
Hanf
G
G
Suttorp
N
N
D000485:Allergens / Q000494:pharmacology*; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D006967:Hypersensitivity / Q000097:blood*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000473:pathology; D020932:Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D000485:Allergens; D019208:Brain-Derived Neurotrophic Factor; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D020932:Nerve Growth Factor