title: IL-22 contributes to TGF-β1-mediated epithelial-mesenchymal transition in asthmatic bronchial epithelial cells.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Meakins-Christie Laboratories, McGill University, 3626 St, Urbain Street, Montréal, QC H2X 2P2, Canada. qutayba.hamid@mcgill.ca.
authors.forename: Jill R
authors.initials: JR
authors.lastname: Johnson
authors.forename: Michiyoshi
authors.initials: M
authors.lastname: Nishioka
authors.forename: Jamila
authors.initials: J
authors.lastname: Chakir
authors.forename: Paul-André
authors.initials: PA
authors.lastname: Risse
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Almaghlouth
authors.forename: Ahmad N
authors.initials: AN
authors.lastname: Bazarbashi
authors.forename: Sophie
authors.initials: S
authors.lastname: Plante
authors.forename: James G
authors.initials: JG
authors.lastname: Martin
authors.forename: David
authors.initials: D
authors.lastname: Eidelman
authors.forename: Qutayba
authors.initials: Q
authors.lastname: Hamid
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001706:Biopsy; D001980:Bronchi / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D015820:Cadherins / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007378:Interleukins / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology / Q000502:physiology*; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D015820:Cadherins; D007378:Interleukins; D055271:Mucin 5AC; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D000097043:Interleukin-22; C524678:MUC5AC protein, human