Barrier responses of human bronchial epithelial cells to grass pollen exposure

Abstract

The airway epithelium forms a physical, chemical and immunological barrier against inhaled environmental substances. In asthma, these barrier properties are thought to be abnormal. In this study, we analysed the effect of grass pollen on the physical and immunological barrier properties of differentiated human primary bronchial epithelial cells.Following exposure to Timothy grass (Phleum pratense) pollen extract, the integrity of the physical barrier was not impaired as monitored by measuring the transepithelial resistance and immunofluorescence staining of tight junction proteins. In contrast, pollen exposure affected the immunological barrier properties by modulating vectorial mediator release. CXC chemokine ligand (CXCL)8/interleukin (IL)-8 showed the greatest increase in response to pollen exposure with preferential release to the apical compartment. Inhibition of the extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase pathways selectively blocked apical CXCL8/IL-8 release via a post-transcriptional mechanism. Apical release of CC chemokine ligand (CCL)20/macrophage inflammatory protein-3a, CCL22/monocyte-derived chemokine and tumour necrosis factor-a was significantly increased only in severe asthma cultures, while CCL11/eotaxin-1 and CXCL10/interferon-c-induced protein-10 were reduced in nonasthmatic cultures.The bronchial epithelial barrier modulates polarised release of mediators in response to pollen without direct effects on its physical barrier properties. The differential response of cells from normal and asthmatic donors suggests the potential for the bronchial epithelium to promote immune dysfunction in asthma. @ERSpublications Bronchial epithelial barrier response to pollen exposure: does bronchial epithelium promote immune dysfunction in asthma?

Novel concepts in airway inflammation and remodelling in asthma

“…Epithelial cells actively secrete immune mediators in response to environmental stimuli [61], which are different in patients with asthma compared with controls [62]. Asthmatic epithelium also has altered barrier function [63], and is a critical bridge between external environmental exposures and pulmonary inflammatory and immune responses [64]. Bronchial epithelial cells dictate downstream responses, despite being structural components of the airway wall and not inflammatory or immune cells.…”

The expression of the eotaxins IL-6 and CXCL8 in human epithelial cells from various levels of the respiratory tract

“…It is known that nitric oxide, prostaglandin E2 and Toll-like receptor 5 regulate CXCL8 expression post-transcriptionally [38][39][40]. It is possible that these mechanisms are ERK1/2-and p38 MAPK-dependent [41]. Pre-stimulation with IFN-γ significantly decreased CCL26 expression and generally increased IL-6 and CXCL8 expression (except for CXCL8 in bronchial cells) after IL-4 or IL-13 stimulation in the nasal, bronchial and small airway epithelial cells.…”

Bronchial epithelium in children: a key player in asthma

“…TEER represents a marker of redifferentiation of the epithelial cells across the cell culture. There are some data from adults [43][44][45][46] showing lower TEER in asthmatic epithelial cultures, but fewer data are available in children. One study, using cultures derived from bronchial brushings, found no significant difference in TEER between asthmatic and non-asthmatic children hemokine gene expression ans laeoinflammatory transcription factors (NF-kB, AP-1 and STAT1/2) chemokine gene expression ans lae [36].…”