IL-22 contributes to TGF-β1-mediated epithelial-mesenchymal transition in asthmatic bronchial epithelial cells

• Published in: Respiratory research Vol. 14; no. 1; p. 118
• Main Authors: Johnson, Jill R, Nishioka, Michiyoshi, Chakir, Jamila, Risse, Paul-André, Almaghlouth, Ibrahim, Bazarbashi, Ahmad N, Plante, Sophie, Martin, James G, Eidelman, David, Hamid, Qutayba
• Format: Journal Article
• Language: English
• Published: London BioMed Central 01.11.2013
• Subjects: Adolescent; Adult; Aged; Asthma - metabolism; Asthma - pathology; Asthma - physiopathology; Biopsy; Bronchi - drug effects; Bronchi - pathology; Bronchi - physiopathology; Cadherins - metabolism; Case-Control Studies; Cells, Cultured; Epithelial Cells - drug effects; Epithelial Cells - pathology; Epithelial Cells - physiology; Epithelial-Mesenchymal Transition - drug effects; Epithelial-Mesenchymal Transition - physiology; Female; Humans; In Vitro Techniques; Interleukin-22; Interleukins - pharmacology; Interleukins - physiology; Male; Medicine; Medicine & Public Health; Middle Aged; Mucin 5AC - metabolism; Phenotype; Pneumology/Respiratory System; RNA, Messenger - metabolism; Severity of Illness Index; Transforming Growth Factor beta1 - pharmacology; Transforming Growth Factor beta1 - physiology; Young Adult; Airway Smooth Muscle; Severe Asthmatic; Allergic Asthma; Bronchial Epithelial Cell; Airway Epithelial Cell
• ISSN: 1465-993X; 1465-9921; 1465-993X
• DOI: 10.1186/1465-9921-14-118

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.