IL-22 contributes to TGF-β1-mediated epithelial-mesenchymal transition in asthmatic bronchial epithelial cells.
Author(s)
Type
Journal Article
Abstract
BACKGROUND: Allergic asthma is characterized by airway inflammation in response to antigen exposure, leading to airway remodeling and lung dysfunction. Epithelial-mesenchymal transition (EMT) may play a role in airway remodeling through the acquisition of a mesenchymal phenotype in airway epithelial cells. TGF-β1 is known to promote EMT; however, other cytokines expressed in severe asthma with extensive remodeling, such as IL-22, may also contribute to this process. In this study, we evaluated the contribution of IL-22 to EMT in primary bronchial epithelial cells from healthy and asthmatic subjects. METHODS: Primary bronchial epithelial cells were isolated from healthy subjects, mild asthmatics and severe asthmatics (n=5 patients per group). The mRNA and protein expression of epithelial and mesenchymal cell markers and EMT-associated transcription factors was evaluated following stimulation with TGF-β1, IL-22 and TGF-β1+IL-22. RESULTS: Primary bronchial epithelial cells stimulated with TGF-β1 underwent EMT, demonstrated by decreased expression of epithelial markers (E-cadherin and MUC5AC) and increased expression of mesenchymal markers (N-cadherin and vimentin) and EMT-associated transcription factors. IL-22 alone had no effect on epithelial or mesenchymal gene expression. However, IL-22+TGF-β1 promoted the expression of some EMT transcription factors (Snail1 and Zeb1) and led to a more profound cadherin shift, but only in cells obtained from severe asthmatics. CONCLUSION: The impact of IL-22 on airway epithelial cells depends on the cytokine milieu and the clinical phenotype of the patient. Further studies are required to determine the molecular mechanism of IL-22 and TGF-β1 cooperativity in driving EMT in primary human bronchial epithelial cells.
Date Issued
2013
Date Acceptance
2013-09-20
Citation
Respiratory Research, 2013, 14, pp.118-118
ISSN
1465-993X
Publisher
BioMed Central
Start Page
118
End Page
118
Journal / Book Title
Respiratory Research
Volume
14
Copyright Statement
© 2013 Johnson et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/24283210
PII: 1465-9921-14-118
Subjects
Adolescent
Adult
Aged
Asthma
Biopsy
Bronchi
Cadherins
Case-Control Studies
Cells, Cultured
Epithelial Cells
Epithelial-Mesenchymal Transition
Female
Humans
In Vitro Techniques
Interleukins
Male
Middle Aged
Mucin 5AC
Phenotype
RNA, Messenger
Severity of Illness Index
Transforming Growth Factor beta1
Young Adult
Coverage Spatial
England