title: Cyclic mechanical stretch down-regulates cathelicidin antimicrobial peptide expression and activates a pro-inflammatory response in human bronchial epithelial cells.
abstract: 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-1β 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.
authors.affiliation: Biomedical Center and Department of Life and Environmental Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Harpa
authors.initials: H
authors.lastname: Karadottir
authors.affiliation: Biomedical Center and Department of Life and Environmental Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Nikhil Nitin
authors.initials: NN
authors.lastname: Kulkarni
authors.affiliation: Stem Cell Research Unit, Biomedical Center, Department of Anatomy, Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.|Department of Laboratory Hematology, Landspitali University Hospital, University of Iceland, Reykjavik, Iceland.
authors.forename: Thorarinn
authors.initials: T
authors.lastname: Gudjonsson
authors.affiliation: Department of Anaesthesia and Intensive Care and Faculty of Medicine, Landspitali University Hospital and University of Iceland, Reykjavik, Iceland.
authors.forename: Sigurbergur
authors.initials: S
authors.lastname: Karason
authors.affiliation: Biomedical Center and Department of Life and Environmental Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Gudmundur Hrafn
authors.initials: GH
authors.lastname: Gudmundsson
keywords: Innate immunity; LL-37; Pro-inflammatory response; Ventilator induced lung injury; Vitamin D3