Dual effect of neutrophils on pIgR/secretory component in human bronchial epithelial cells: role of TGF-beta.
J Biomed Biotechnol
; 20102010.
Article
in En
| MEDLINE
| ID: mdl-20706611
ABSTRACT
Neutrophils have a dual affect on epithelial pIgR/SC, the critical receptor for transcellular routing of mucosal IgA, but mechanisms of pIgR/SC upregulation remain elusive. Requirements of cytokine, redox, and signalling pathways for pIgR/SC production were assessed in human bronchial epithelial (Calu-3) cells cocultured with increasing numbers of blood neutrophils. Increased SC production was observed after incubation for 48 hrs with intermediate neutrophil numbers (1.25 to 2.5 x 10(6)), was favoured by the elastase inhibitor SLPI, and correlated with increased TGF-beta production. Exogenous TGF-beta stimulated SC production with a maximal effect at 48 hrs and both TGF-beta- and neutrophil-driven SC upregulation were dependent on redox balance and p38 MAP-kinase activation. This paper shows that activated neutrophils could upregulate epithelial pIgR/SC production through TGF-beta-mediated activation of a redox-sensitive and p38 MAPK-dependent pathway. An imbalance between the two neutrophil-driven opposite mechanisms (SC upregulation and SC degradation) could lead to downregulation of pIgR/SC, as observed in severe COPD.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bronchi
/
Secretory Component
/
Transforming Growth Factor beta
/
Receptors, Polymeric Immunoglobulin
/
Respiratory Mucosa
/
Neutrophils
Limits:
Humans
Language:
En
Journal:
J Biomed Biotechnol
Journal subject:
BIOTECNOLOGIA
/
MEDICINA
Year:
2010
Type:
Article
Affiliation country:
Belgium