American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Sep 2014
Polymeric Immunoglobulin Receptor Downregulation in COPD: Persistence in the Cultured Epithelium and Role of Transforming Growth Factor-β.
The generation of protective secretory IgA relies on the epithelial polymeric immunoglobulin receptor (pIgR). pIgR expression is reduced in chronic obstructive pulmonary disease (COPD), but correlation to disease severity and underlying mechanisms remains unknown. ⋯ pIgR down-regulation in COPD correlates with disease severity, and the bronchial epithelium reconstituted in vitro from these patients retains its aberrant imprinting for pIgR expression. This study also links pIgR down-regulation to TGF-β-driven reprogramming of the bronchial epithelium, which results in impaired lung IgA immunity in patients with COPD.
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Am. J. Respir. Crit. Care Med. · Sep 2014
A Novel TNF-mediated Mechanism of Direct Epithelial Sodium Channel Activation.
Alveolar liquid clearance is regulated by Na(+) uptake through the apically expressed epithelial sodium channel (ENaC) and basolaterally localized Na(+)-K(+)-ATPase in type II alveolar epithelial cells. Dysfunction of these Na(+) transporters during pulmonary inflammation can contribute to pulmonary edema. ⋯ These results demonstrate a novel TNF-mediated mechanism of direct ENaC activation and indicate a physiological role for the lectin-like domain of TNF in the resolution of alveolar edema during inflammation.