Mechanical stretch enhances IL-8 production in pulmonary microvascular endothelial cells.
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.
Iwaki
Mai
M
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Ito
Satoru
S
Morioka
Masataka
M
Iwata
Susumu
S
Numaguchi
Yasushi
Y
Ishii
Masakazu
M
Kondo
Masashi
M
Kume
Hiroaki
H
Naruse
Keiji
K
Sokabe
Masahiro
M
Hasegawa
Yoshinori
Y
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
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