Epithelial-Derived Inflammation Disrupts Elastin Assembly and Alters Saccular Stage Lung Development.

Epithelial-Derived Inflammation Disrupts Elastin Assembly and Alters Saccular Stage Lung Development. Am J Pathol. 2016 May 12; Authors: Benjamin JT, van der Meer R, Im AM, Plosa EJ, Zaynagetdinov R, Burman A, Havrilla ME, Gleaves LA, Polosukhin VV, Deutsch GH, Yanagisawa H, Davidson JM, Prince LS, Young LR, Blackwell TS Abstract The highly orchestrated interactions between the epithelium and mesenchyme required for normal lung development can be disrupted by perinatal inflammation in preterm infants, although the mechanisms are incompletely understood. We used transgenic (inhibitory κB kinase transactivated) mice that conditionally express an activator of the NF-κB pathway in airway epithelium to investigate the impact of epithelial-derived inflammation during lung development. Epithelial NF-κB activation selectively impaired saccular stage lung development, with a phenotype comprising rapidly progressive distal airspace dilation, impaired gas exchange, and perinatal lethality. Epithelial-derived inflammation resulted in disrupted elastic fiber organization and down-regulation of the elastin assembly components, including fibulins 4 and 5, lysyl oxidase like-1, and fibrillin-1. Fibulin-5 expression by saccular stage lung fibroblasts was consistently inhibited by treatment with bronchoalveolar lavage fluid from inhibitory κB kinase transactivated mice, Escherichia coli lipopolysaccharide, or tracheal aspirates from preterm infant...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research