Regulation of NGF and BDNF by dexamethasone and theophylline in human peripheral eosinophils in allergics and non-allergics.
BACKGROUND
Recent studies have shown that the neurotrophins NGF and BDNF are produced by eosinophils. The influence of neurotrophins in allergic diseases including asthma has been described. The regulation by pharmacological substance remains unclear.


OBJECTIVE
The aim of this study was to assess whether approved pharmacological substances in the treatment of asthma such as corticosteroids or theophylline regulate neurotrophins on a cellular level.


METHODS
Eosinophils were purified by negative immunoselection from allergics and non-allergic donors. Eosinophils were incubated with dexamethasone and theophylline and supernatants were collected for measurement of neurotrophic factors. The content of neurotrophins in eosinophil lysates was determined by ELISA. Regulation of stored NGF and BDNF was demonstrated by Western-blotting and flow cytometry while influence on transcription level was demonstrated by RT-PCR.


RESULTS
Eosinophils produce and release the neurotrophins NGF and BDNF at different levels in allergics and non-allergics. Dexamethason lead to a significant downregulation of NGF in eosinophils of allergics. The levels of BDNF were not significantly reduced. Theophylline did not influence the levels of NGF nor BDNF significantly.


CONCLUSIONS
The production of the neurotrophin NGF was downregulated by an established substance such as dexamethasone. This might further contribute to the pharmacological potential of corticosteroids in allergic asthma.
Noga
Oliver
O
Allergy and Asthma Clinic, Dept. of Medicine Infectious and Respiratory Diseases, Charité, Virchow Klinikum, Humboldt University, Augustenburger Platz 1, Berlin 13353, Germany. oliver.noga@charite.de
Hanf
Gerald
G
Görges
Dunja
D
Dinh
Q Thai
QT
Groneberg
David A
DA
Suttorp
Norbert
N
Kunkel
Gert
G
D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D001993:Bronchodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020932:Nerve Growth Factor / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology* / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D019208:Brain-Derived Neurotrophic Factor; D001993:Bronchodilator Agents; D003907:Dexamethasone; D020932:Nerve Growth Factor; D013806:Theophylline