Mechanical stress upregulates intercellular adhesion molecule-1 in pulmonary epithelial cells.
BACKGROUND
Mechanical ventilation can affect the lung, causing edema and alveolar inflammation. Intercellular adhesion molecule-1 (ICAM-1) plays an important role in this inflammatory response.


OBJECTIVE
The aims of this study were to investigate whether cyclic cell stretch upregulates the production of ICAM-1 by human alveolar epithelium and to explore possible mechanisms of upregulation.


METHODS
Human type 2-like alveolar epithelial cells (A549 cells) were exposed to cyclic tensile strain via a four-point bending system, with strains of varying frequency (0.2, 0.5, and 1 Hz), duration (0, 1, 3, and 6 h), and magnitude (500, 1,000, and 2,000 microstrain). Strain was applied at varying frequency (0.2, 0.5, 1 Hz) but at constant time (3 h) and magnitude (1,000 microstrain), at varying duration (0, 1, 3, and 6 h) but at constant frequency (0.5 Hz) and magnitude (1,000 microstrain), or at varying magnitude (500, 1,000, and 2,000 microstrain) but at constant time (3 h) and frequency (0.5 Hz).


RESULTS
Mechanical loading induced ICAM-1 protein and mRNA production in a frequency- and duration-dependent manner. At the 3-hour time point, large loadings (1,000 or 2,000 microstrain) upregulated ICAM-1 protein production, but there was no statistically significant difference between these two groups (p > 0.05). PD98059, a specific inhibitor of extracellular signal-regulated kinase (ERK), and N-acetylcysteine (NAC), an antioxidant, partially abrogated the stretch-induced ICAM-1 protein upregulation at the 3-hour loading.


CONCLUSIONS
Mechanical strain can upregulate ICAM-1 production. The response is frequency and duration dependent, which may involve both ERK pathways and reactive oxidant species production.
Hu
Xiaobo
X
Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, PR China.
Zhang
Youyi
Y
Cheng
Deyun
D
Ding
Yu
Y
Yang
Dongmei
D
Jiang
Fei
F
Zhou
Chao
C
Ying
Binwu
B
Wen
Fuqiang
F
D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology*
D000975:Antioxidants; D005419:Flavonoids; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000111:Acetylcysteine