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. OBJECTIVES: 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.
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. OBJECTIVES: 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.
Authors: Erin L Foster; Eric L Simpson; Lorna J Fredrikson; James J Lee; Nancy A Lee; Allison D Fryer; David B Jacoby Journal: PLoS One Date: 2011-07-21 Impact factor: 3.240