Monocyte interaction accelerates HCl-induced lung epithelial remodeling

BMC Pulmonary Medicine

Haibo Zhang⁴  Arthur S Slutsky¹  Bruce Hsin-Kuo Ko³  Bing Han²  Haibo Qiu⁵  Alice Aili Luo²  Qiuhua Chen⁵ 

[1] Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada;Keenan Research Center for Biomedical Science of St. Michael’s Hospital, Toronto, Ontario, Canada;Department of Respiratory Therapy, Taipei Veterans General Hospital and Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan;Department of Anesthesia and Department of Physiology, University of Toronto, Room 619, LKSKI, 209 Victoria St, Toronto, Ontario M5B 1T8, Canada;Department of Critical Care Medicine, Nanjing Zhong-Da Hospital, Southeast University School of Medicine, Nanjing, PR China

关键词: EMT;    Chemokine;    PDGF;    ARDS;   

Others  :  1109550
DOI  :  10.1186/1471-2466-14-135

 received in 2013-09-11, accepted in 2014-07-31,  发布年份 2014

【 摘 要 】

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 CD11a_237–246 or/and CD18_112–122 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.

【 授权许可】

   
2014 Chen et al.; licensee BioMed Central Ltd.

【 图 表 】

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