Dual Effect of Neutrophils on pIgR/Secretory Component in Human Bronchial Epithelial Cells: Role of TGF-beta.
(2010) Journal of Biomedicine and Biotechnology — Vol. 2010 (2010)
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- 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.
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Ratajczak, C., Pilette, C., Guisset, A., Detry, B., & Sibille, Y. (2010). Dual Effect of Neutrophils on pIgR/Secretory Component in Human Bronchial Epithelial Cells: Role of TGF-beta. Journal of Biomedicine and Biotechnology, 2010. https://doi.org/10.1155/2010/428618 (Original work published 2010)