The Contribution of the Airway Epithelial Cell to Host Defense

Abstract

In the context of cystic fibrosis, the epithelial cell has been characterized in terms of its ion transport capabilities. The ability of an epithelial cell to initiate CFTR-mediated chloride and bicarbonate transport has been recognized early as a means to regulate the thickness of the epithelial lining fluid and recently as a means to regulate the pH, thereby determining critically whether or not host defense proteins such as mucins are able to fold appropriately. This review describes how the epithelial cell senses the presence of pathogens and inflammatory conditions, which, in turn, facilitates the activation of CFTR and thus directly promotes pathogens clearance and innate immune defense on the surface of the epithelial cell. This paper summarizes functional data that describes the effect of cytokines, chemokines, infectious agents, and inflammatory conditions on the ion transport properties of the epithelial cell and relates these key properties to the molecular pathology of cystic fibrosis. Recent findings on the role of cystic fibrosis modifier genes that underscore the role of the epithelial ion transport in host defense and inflammation are discussed.

Casticin inhibits interleukin-1β-induced ICAM-1 and MUC5AC expression by blocking NF-κB, PI3K-Akt, and MAPK signaling in human lung epithelial cells

“…These lung diseases involve relatively more mucin secretion in the epithelial layers of airways. Cilia are the principal cells on the surface epithelium of intrapulmonary airways for excluding inhaled microbes and dust [ 50 , 51 ]. Epithelial cells also release more antimicrobial molecules, including IgA and lysozyme, against microbial infections [ 1 ].…”

“…Neutrophils are essential for removing bacterial infections in acute inflammatory lung disease [ 31 ]. Lung epithelial cells of patients release IL-8 to attract more neutrophils against microbe infection [ 54 ], and inflammatory epithelial cells secrete more IL-1β, IL-6, TNF-α, CCL5, MCP-1, and IL-17 to activate the inflammatory warning signal [ 51 ]. However, those inflammatory responses of the airways also can cause lung injury and physical discomfort.…”

Epithelial Anion Transport as Modulator of Chemokine Signaling

“…These inflammatory mediators in concert with the production of reactive oxygen species (ROS) allow the epithelium to contribute to the host defense and to recruit specialized immune cells [ 4 – 7 ]. It is well established that the expression and function of ion channels and transporters, including the anion channel and transporters discussed in this review, are modulated by chemokines and cytokines [ 8 – 12 ]. Examples for these mechanisms include the inhibition and downregulation of the epithelial sodium channel (ENaC) by IL-4 and IL-13 [ 10 , 13 , 14 ], the IL-4 and IL-13-mediated increase in function and expression of CFTR [ 13 ], and TMEM16A [ 15 ] as well as pendrin (SLC26A4) [ 12 , 16 ] and SLC26A9 [ 17 ].…”

Biologicals in der Rhinologie – Individualisierte Konzepte der Zukunft

“…The cilia have multiple functions; it could be shown among others that they are chemosensory. At the same time, the intact respiratory epithelium is the basis for functionally intact defense 54 55 . At transition points to enhanced mechanical use, e. g., in the pharynx, the epithelium merges into a stratified squamous epithelium.…”

“…Die Zilien übernehmen multiple Funktionen, u. a. konnte gezeigt werden, dass sie chemosensorisch sind. Zugleich ist das intakte respiratorische Epithel die Grundlage für funktionell intakte Abwehrfunktionen 54 55 . An Stellen im Übergang zu verstärkter mechanischer Beanspruchung z.…”