title: Monocyte interaction accelerates HCl-induced lung epithelial remodeling.
abstract: BACKGROUND
  Acute respiratory distress syndrome (ARDS) is characterized by overwhelming inflammatory responses and lung remodeling. We hypothesized that leukocyte infiltration during the inflammatory response modulates epithelial remodeling through a mechanism of epithelial-mesenchymal transition (EMT).
  
  
  METHODS
  Human lung epithelial cells were treated for 30 min with hydrochloric acid (HCl). Human monocytes were then cocultured with the epithelial cells for up to 48 h, in the presence or absence of blocking peptides against lymphocyte function-associated antigen-1 (LFA-1), or tyrphostin A9, a specific inhibitor for platelet-derived growth factor (PDGF) receptor tyrosine kinase.
  
  
  RESULTS
  Exposure of lung epithelial cells to HCl resulted in increased expression of intercellular adhesion molecule-1 (ICAM-1) and production of interleukin (IL)-8 at 24 h. The expression of the epithelial markers E-cadherin decreased while the mesenchymal markers vimentin and α-smooth muscle actin (α-SMA) increased at 24 h and remained high at 48 h. The addition of monocytes augmented the profiles of lower expression of epithelial markers and higher mesenchymal markers accompanied by increased collagen deposition. This EMT profile was associated with an enhanced production of IL-8 and PDGF. Treatment of the lung epithelial cells with the LAF-1 blocking peptides CD11a237-246 or/and CD18112-122 suppressed monocyte adhesion, production of IL-8, PDGF and hydroxyproline as well as EMT markers. Treatment with tyrphostin A9 prevented the EMT profile shift induced by HCl stimulation.
  
  
  CONCLUSIONS
  The interaction between epithelial cells and monocytes enhanced epithelial remodelling after initial injury through EMT signalling that is associated with the release of soluble mediators, including IL-8 and PDGF.
authors.forename: Qiuhua
authors.initials: Q
authors.lastname: Chen
authors.forename: Alice Aili
authors.initials: AA
authors.lastname: Luo
authors.forename: Haibo
authors.initials: H
authors.lastname: Qiu
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Bruce Hsin-Kuo
authors.initials: BH
authors.lastname: Ko
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Slutsky
authors.affiliation: Keenan Research Center for Biomedical Science of St, Michael's Hospital, Toronto, Ontario, Canada. zhangh@smh.ca.
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000199:Actins / Q000378:metabolism; D056809:Alveolar Epithelial Cells / Q000378:metabolism* / Q000473:pathology* / Q000502:physiology; D040881:CD11a Antigen; D018821:CD18 Antigens; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D006851:Hydrochloric Acid / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000187:drug effects / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects; D009000:Monocytes; D010455:Peptides / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000187:drug effects / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D040881:CD11a Antigen; D018821:CD18 Antigens; D015820:Cadherins; D016209:Interleukin-8; D016169:Lymphocyte Function-Associated Antigen-1; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D020032:Tyrphostins; D014746:Vimentin; C406122:tyrphostin A9; D018799:Intercellular Adhesion Molecule-1; D006851:Hydrochloric Acid
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