Abstract
Exposure and sensitivity to ubiquitous airborne fungi such as Alternaria alternata have long been implicated in the development, onset, and exacerbation of chronic allergic airway disorders. This present study is the first to investigate global changes in host gene expression during the interaction of cultured human bronchial epithelial cells and live Alternaria spores. In in vitro experiments human bronchial epithelial cells (BEAS-2B) were exposed to spores or media alone for 24 h. RNA was collected from three biological replicates per treatment and was used to assess changes in gene expression patterns using Affymetrix Human Genome U133 Plus 2.0 Arrays. In cells treated with Alternaria spores compared to controls, 613 probe sets representing 460 individual genes were found differentially expressed (p ≤ 0.05). In this set of 460 statistically significant, differentially expressed genes, 397 genes were found to be up-regulated and 63 were down-regulated. Of these 397 up-regulated genes, 156 genes were found to be up-regulated ≥2 fold. Interestingly, none of the 63 down-regulated genes were found differentially expressed at ≤−2 fold. Differentially expressed genes were identified following statistical analysis and subsequently used for pathway and network evaluation. Interestingly, many cytokine and chemokine immune response genes were up-regulated with a particular emphasis on interferon-inducible genes. Genes involved in cell death, retinoic acid signaling, and TLR3 response pathways were also significantly up-regulated. Many of the differentially up-regulated genes have been shown in other systems to be associated with innate immunity, inflammation and/or allergic airway diseases. This study now provides substantial information for further investigating specific genes and innate immune system pathways activated by Alternaria in the context of allergic airway diseases.
Highlights
The airway epithelium has long been considered a physiochemical barrier characterized by having tight junctions or producing proteins and/or enzymes that collectively constitute a protective environment
This innate immune response often includes the production of a variety of cytokines, chemokines, extracellular matrix and growth factors that may function to recruit other effector cells such as macrophages, neutrophils, eosinophils, and lymphocytes and shape the development of adaptive immune responses associated with complex allergic diseases like allergic or atopic asthma (Mills et al, 1999; Shin and Lee, 2010)
In order to investigate global gene expression changes in airway epithelial cells in response to Alternaria we performed a comparative microarray analysis of a human bronchial epithelial cell line (BEAS-2B) stimulated with live spores of A. alternata with untreated cells serving as the control
Summary
The airway epithelium has long been considered a physiochemical barrier characterized by having tight junctions or producing proteins and/or enzymes that collectively constitute a protective environment. Respiratory epithelial cells play an active role in innate immunity via recognition and response to pathogen associated molecular patterns (PAMPs) and/or specific pathogen-secreted immunogenic proteins This innate immune response often includes the production of a variety of cytokines, chemokines, extracellular matrix and growth factors that may function to recruit other effector cells such as macrophages, neutrophils, eosinophils, and lymphocytes and shape the development of adaptive immune responses associated with complex allergic diseases like allergic or atopic asthma (Mills et al, 1999; Shin and Lee, 2010). Human airways are continuously exposed to ubiquitous environmental fungal spores and hyphae. This exposure often occurs at a higher level and for a longer duration than that of pollen or other types of airborne allergen sources. The most common airborne fungi include species found within the genera Cladosporium, Alternaria, Penicillium, and Aspergillus, a multitude of other species are commonly found in any type of environment and climate (Al-Doory and Domson, 1984; Bowyer and Denning, 2007)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
