Chemokine expression in the early response to injury in human airway epithelial cells.

Bingqing Xie,Bharathi Laxman,Natalia Maltsev,Randi Stern,Steven R White,Somaye Hashemifar,T Conrad Gilliam

doi:10.1371/journal.pone.0193334

Abstract

Basal airway epithelial cells (AEC) constitute stem/progenitor cells within the central airways and respond to mucosal injury in an ordered sequence of spreading, migration, proliferation, and differentiation to needed cell types. However, dynamic gene transcription in the early events after mucosal injury has not been studied in AEC. We examined gene expression using microarrays following mechanical injury (MI) in primary human AEC grown in submersion culture to generate basal cells and in the air-liquid interface to generate differentiated AEC (dAEC) that include goblet and ciliated cells. A select group of ~150 genes was in differential expression (DE) within 2–24 hr after MI, and enrichment analysis of these genes showed over-representation of functional categories related to inflammatory cytokines and chemokines. Network-based gene prioritization and network reconstruction using the PINTA heat kernel diffusion algorithm demonstrated highly connected networks that were richer in differentiated AEC compared to basal cells. Similar experiments done in basal AEC collected from asthmatic donor lungs demonstrated substantial changes in DE genes and functional categories related to inflammation compared to basal AEC from normal donors. In dAEC, similar but more modest differences were observed. We demonstrate that the AEC transcription signature after MI identifies genes and pathways that are important to the initiation and perpetuation of airway mucosal inflammation. Gene expression occurs quickly after injury and is more profound in differentiated AEC, and is altered in AEC from asthmatic airways. Our data suggest that the early response to injury is substantially different in asthmatic airways, particularly in basal airway epithelial cells.

Highlights

The epithelium lining human lung airways serves as a primary defense interface against particulates, inhaled pollutants, pathogens, and xenobiotics
To address the questions related to the early events that occur after injury, we examined epithelial cell expression in a well-established mechanical injury model in both normal and asthmatic airway epithelial cells (AEC) grown under two distinct conditions: (1) in submersion culture with uniformly basal AEC phenotype, and (2) in air-liquid interface (ALI) culture that generates a more differentiated AEC phenotype seen in a homeostatic airway
Epithelial transcriptomes of normal un-injured basal AEC and differentiated AEC (dAEC) are different under standard quiescent culture

Summary

Introduction

The epithelium lining human lung airways serves as a primary defense interface against particulates, inhaled pollutants, pathogens, and xenobiotics. Basal airway epithelial cells (AEC) comprise approximately 30 percent of the epithelium in the major airways. These cells operate as the progenitors for ciliated and goblet columnar cells within the airway [1,2,3], especially after.

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Conclusion