title: Mechanical stretch enhances IL-8 production in pulmonary microvascular endothelial cells.
abstract: In patients with acute respiratory distress syndrome, mechanical over-distension of the lung by a large tidal volume causes further damage and inflammation, called ventilator-induced lung injury (VILI), however, it is unclear how mechanical stretch affects the cellular functions or morphology in human pulmonary microvascular endothelial cells (HPMVECs). IL-8 has been proposed to play an important role in the progression of VILI by activating neutrophils. We demonstrated that HPMVECs exposed to cyclic uni-axial stretch produce IL-8 protein with p38 activation in strain- and time-dependent manners. The IL-8 synthesis was not regulated by other signal transduction pathways such as ERK1/2, JNK, or stretch-activated Ca(2+) channels. Moreover, cyclic stretch enhanced IL-6 and monocyte chemoattractant protein-1 production and reoriented cell perpendicularly to the stretch axis accompanied by actin polymerization. Taken together, IL-8 production by HPMVECs due to excessive mechanical stretch may activate neutrophilic inflammation, which leads to VILI.
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Iwaki
authors.forename: Satoru
authors.initials: S
authors.lastname: Ito
authors.forename: Masataka
authors.initials: M
authors.lastname: Morioka
authors.forename: Susumu
authors.initials: S
authors.lastname: Iwata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Numaguchi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ishii
authors.forename: Masashi
authors.initials: M
authors.lastname: Kondo
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kume
authors.forename: Keiji
authors.initials: K
authors.lastname: Naruse
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sokabe
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hasegawa
mesh_terms: D002118:Calcium / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism / Q000503:physiopathology; D002460:Cell Line; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D008168:Lung / Q000378:metabolism / Q000503:physiopathology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D013314:Stress, Mechanical; D055397:Ventilator-Induced Lung Injury / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016209:Interleukin-8; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D002118:Calcium