BDNF and DPP-IV in polyps and middle turbinates epithelial cells.
OBJECTIVE
Neuropeptides released from sensory nerves may contribute to airway inflammation, particularly if their metabolism is impaired through defective inactivation and/or increased production. In the airways, neuropeptides are subjected to degradation by enzymes such as dipeptidyl peptidase (DPP-IV), and are upregulated by neurotrophins such as brain derived neurotrophic factor (BDNF). We therefore assessed in primary human nasal epithelial cells the expression of DPP-IV and BDNF under basal and inflammatory conditions.


METHODS
Human epithelial cells were isolated from nasal polyps and middle turbinates, and grown on collagen-coated polycarbonate filters with an air liquid-interface. After three weeks of culture, constitutive cellular expression of DPP-IV and BDNF was assessed by measuring its activity and by ELISA, respectively. To mimick in vivo inflammatory conditions, cells were exposed apically and basolaterally to 50 ng/ml of TNFalpha, IL-1beta, and IFN-gamma for two days. DPP-IV activity and BDNF protein expression were measured in cell lysates and in the apical and basolateral media.


RESULTS
Constitutive DPP-IV activity was similar in polyps and turbinates cells. In contrast, polyps epithelial cells expressed higher amounts of BDNF compared to turbinates derived cells. On the other hand, TNFalpha, IL-1beta, and IFN-gamma did not affect DPP-IV activity but significantly increased the cellular expression and the basolateral secretion of BDNF.


CONCLUSIONS
Our data show for the first time that primary human airway epithelial cells produced DPP-IV and BDNF under basal conditions. Furthermore, the production and secretion of BDNF were markedly increased in response to pro-inflammatory cytokines, confirming the involvement of BDNF in airway inflammation.
Jornot
L
L
Respiratory Division, Department of Internal Medicine, University Hospitals, Geneva, Switzerland. Lan.H.Jornot@hcuge.ch
Grouzmann
E
E
Lacroix
J S
JS
Rochat
T
T
D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000096:biosynthesis*; D002478:Cells, Cultured; D018819:Dipeptidyl Peptidase 4 / Q000032:analysis / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009296:Nasal Cavity / Q000166:cytology*; D009298:Nasal Polyps / Q000737:chemistry / Q000378:metabolism*; D014420:Turbinates
D019208:Brain-Derived Neurotrophic Factor; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4