Cyclic mechanical stretch down-regulates cathelicidin antimicrobial peptide expression and activates a pro-inflammatory response in human bronchial epithelial cells

• Published in: PeerJ
• Main Authors: Karadottir, Harpa, Kulkarni, Nikhil Nitin, Gudjonsson, Thorarinn, Karason, Sigurbergur, Gudmundsson, Gudmundur Hrafn
• Other Authors: 1 Univ Iceland, Biomed Ctr, Reykjavik, Iceland 2 Univ Iceland, Dept Life & Environm Sci, Reykjavik, Iceland 3 Univ Iceland, Sch Hlth Sci, Fac Med, Biomed Ctr,Dept Anat,Stem Cell Res Unit, Reykjavik, Iceland 4 Univ Iceland, Landspitali Univ Hosp, Dept Lab Hematol, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital University of Iceland 5 Landspitali Univ Hosp, Dept Anaesthesia & Intens Care, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital 6 Landspitali Univ Hosp, Fac Med, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital University of Iceland 7 Univ Iceland, Reykjavik, Iceland, Biomedical Center and Department of Life and Environmental Sciences, University of Iceland, Reykjavik, Iceland, Stem Cell Research Unit, Biomedical Center, Department of Anatomy, Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland, Department of Anaesthesia and Intensive Care and Faculty of Medicine, Landspitali University Hospital and University of Iceland, Reykjavik, Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: Peer J Inc 2015
• Subjects: Immunity; Innate; Ventilator-Induced Lung Injury; Vitamin D3 24-Hydroxylase; Iceland
• Online Access: http://hdl.handle.net/2336/592985; https://doi.org/10.7717/peerj.1483

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. Mechanical ventilation (MV) of patients can cause damage to bronchoalveolar epithelium, leading to a sterile inflammatory response, infection and in severe cases sepsis. Limited knowledge is available on the effects of MV on the innate immune defense system in the human lung. In this study, we demonstrate that cyclic stretch of the human bronchial epithelial cell lines VA10 and BCi NS 1.1 leads to down-regulation of cathelicidin antimicrobial peptide ( CAMP ) gene expression. We show that treatment of VA10 cells with vitamin D3 and/or 4-phenyl butyric acid counteracted cyclic stretch mediated down-regulation of CAMP mRNA and protein expression (LL-37). Further, we observed an increase in pro-inflammatory responses in the VA10 cell line subjected to cyclic stretch. The mRNA expression of the genes encoding pro-inflammatory cytokines IL-8 and IL-1 β was increased after cyclic stretching, where as a decrease in gene expression of chemokines IP-10 and RANTES was observed. Cyclic stretch enhanced oxidative stress in the VA10 cells. The mRNA expression of toll-like receptor ( TLR ) 3 , TLR5 and TLR8 was reduced, while the gene expression of TLR2 was increased in VA10 cells after cyclic stretch. In conclusion, our in vitro results indicate that cyclic stretch may differentially modulate innate immunity by down-regulation of antimicrobial peptide expression and increase in pro-inflammatory responses. LSH (Landspitali University Hospital) Ossur hf Oddur Olafsson fund University of Iceland RANNIS