Dual effect of neutrophils on pIgR/secretory component in human bronchial epithelial cells: role of TGF-beta.
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.
Ratajczak
Céline
C
Institute of Experimental and Clinical Research, Pole Pneumology, ENT and Dermatology, Cliniques Universitaires St-Luc, Université Catholique de Louvain (UCL), Brussels B-1200, Belgium.
Guisset
Amélie
A
Detry
Bruno
B
Sibille
Yves
Y
Pilette
Charles
C
D001980:Bronchi / Q000166:cytology / Q000276:immunology*; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D009504:Neutrophils / Q000276:immunology*; D010084:Oxidation-Reduction; D019056:Receptors, Polymeric Immunoglobulin / Q000276:immunology*; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D012635:Secretory Component / Q000276:immunology*; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000494:pharmacology; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D019056:Receptors, Polymeric Immunoglobulin; C506814:SLPI protein, human; D012635:Secretory Component; D053481:Secretory Leukocyte Peptidase Inhibitor; D016212:Transforming Growth Factor beta