Dual effect of neutrophils on pIgR/secretory component in human bronchial epithelial cells: Role of TGF-β

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 48hrs with intermediate neutrophil numbers (1.25 to 2.5 10 6), was favoured by the elastase inhibitor SLPI, and correlated with increased TGF-β production. Exogenous TGF-β stimulated SC production with a maximal effect at 48hrs and both TGF-β - 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-β -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. Copyright © 2010 Céline Ratajczak et al.