Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2014 Feb 3;9(2):e87768.
doi: 10.1371/journal.pone.0087768. eCollection 2014.

High degree of overlap between responses to a virus and to the house dust mite allergen in airway epithelial cells

Korneliusz Golebski  1 , Silvia Luiten  1 , Danielle van Egmond  1 , Esther de Groot  1 , Kristina Irene Lisolette Röschmann  1 , Wytske Johanna Fokkens  1 , Cornelis Maria van Drunen  1
Affiliations
Comparative Study

High degree of overlap between responses to a virus and to the house dust mite allergen in airway epithelial cells

Korneliusz Golebski et al. PLoS One. .

Abstract

Background: Airway epithelium is widely considered to play an active role in immune responses through its ability to detect changes in the environment and to generate a microenvironment for immune competent cells. Therefore, besides its role as a physical barrier, epithelium affects the outcome of the immune response by the production of various pro-inflammatory mediators.

Methods: We stimulated airway epithelial cells with viral double stranded RNA analogue poly(I:C) or with house dust mite in a time course of 24 hours. In order to determine cytokines production by stimulated cells, we performed multiplex enzyme linked immunosorbant assay (ELISA).

Results: We demonstrate that the temporal pattern of the genes that respond to virus exposure in airway epithelium resembles to a significant degree their pattern of response to HDM. The gene expression pattern of EGR1, DUSP1, FOSL1, JUN, MYC, and IL6 is rather similar after viral (poly(I:C)) and HDM exposure. However, both triggers also induce a specific response (e.g. ATF3, FOS, and NFKB1). We confirmed these data by showing that epithelial cells produce a variety of similar mediators in response to both poly(I:C) and HDM challenge (IL1-RA, IL-17, IFN-α and MIP1-α), sometimes with a quantitative difference in response (IL2-R, IL-6, IL-8, MCP-1, MIG, and HGF). Interestingly, only four mediators (IL-12, IP-10, RANTES and VEGF) where up-regulated specifically by poly(I:C) and not by HDM. Additionally, we report that pre-exposure to HDM deregulates production of cytokines and mediators in response to poly(I:C).

Conclusions: Epithelial cells responses to the HDM-allergen and a virus strongly resemble both in gene expression and in protein level explaining why these two responses may affect each other.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: WF and CvD have received private sector support for research and/or clinical trials related to treatment of allergic and non-allergic rhinitis by Allergopharma, ALK-Abello, GlaxoSmithKline, HAL Allergy, MSD, Optinose UK, and public sector research support by InterUniversity Attraction Poles (Belgium), ZonMW (The Netherlands), and Global Allergy and Asthma European Network (EU). The authors declare that this does not alter their adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Network interaction model of the genes that make up the core response of airway epithelial cells upon HDM allergen exposure.
The principal cellular locations of the gene products (extra cellular region, membrane, cytoplasm, and nucleus) are indicated and their transcriptional interaction.
Figure 2
Figure 2. Detailed expression analysis of selected genes in response to HDM challenge.
The NCI-H292 cell line was stimulated with HDM in a time course over 24 hours and expression profiles of: ATF3, EGR1, DUSP1, FOS, FOSL1, MYC, JUN, IL6, NKB1, and NFKB2 were investigated. Graphs show genes that are: A) induced rapidly upon HDM stimulation; B) induced 2 hours after HDM; C) late-induced; D) not affected by HDM stimulation. Each time point represents an average of three biological replicates ± standard deviation.
Figure 3
Figure 3. Detailed expression analysis of selected genes in response to poly(I:C) challenge.
The NCI-H292 cell line was stimulated with poly(I:C) in a time course over 24 hours and expression profiles of: ATF3, EGR1, DUSP1, FOS, FOSL1, MYC, JUN, IL6, NKB1, and NFKB2 were investigated. Graphs show genes that are: A) induced rapidly after stimulation with poly(I:C); B) induced 2 hours after poly(I:C); C) late-induced; D) not affected by poly(I:C) stimulation. Each time point represents an average of three biological replicates ± standard deviation.
Figure 4
Figure 4. Detailed gene expression analysis.
Temporal patterns of genes: A) and B): differentially expressed after stimulation with HDM or poly(I:C); C) with similar expression pattern triggered by HDM or poly(I:C). Each time point represents an average value of three biological replicates ± standard deviation. Statistically significant differences (p<0.05) in the gene up-regulation levels between HDM and poly(I:C) stimulation are indicated (*).
See this image and copyright information in PMC

References

    1. Vroling AB, Fokkens WJ, van Drunen CM (2008) How epithelial cells detect danger: aiding the immune response. Allergy 63: 1110–1123. - PubMed
    1. Roschmann K, Farhat K, Konig P, Suck R, Ulmer AJ, et al. (2009) Timothy grass pollen major allergen Phl p 1 activates respiratory epithelial cells by a non-protease mechanism. Clin Exp Allergy 39: 1358–1369. - PubMed
    1. Roschmann KI, van Kuijen AM, Luiten S, Jonker MJ, Breit TM, et al. (2012) Purified Timothy grass pollen major allergen Phl p 1 may contribute to the modulation of allergic responses through a pleiotropic induction of cytokines and chemokines from airway epithelial cells. Clin Exp Immunol 167: 413–421. - PMC - PubMed
    1. Toppila-Salmi S, Renkonen J, Joenvaara S, Mattila P, Renkonen R (2011) Allergen interactions with epithelium. Curr Opin Allergy Clin Immunol 11: 29–32. - PubMed
    1. Golebski K, Roschmann KI, Toppila-Salmi S, Hammad H, Lambrecht BN, et al. (2013) The multi-faceted role of allergen exposure to the local airway mucosa. Allergy 68: 152–160. - PubMed

Publication types

MeSH terms