[Engagement of p38 mitogen-activated protein kinase in regulation of epithelial barrier of acute respiratory distress syndrome].
OBJECTIVE
To observe airway epithelial barrier dysfunction in acute respiratory distress syndrome (ARDS), and the possible regulatory role of p38 mitogen-activated protein kinase (p38MAPK).


METHODS
The primary human trachea-bronchial epithelial cells were incubated either in 1 f.Lg/mL lipopolysaccharide (LPS) , I J.Lg/mLLPS + 10 nmol/L p38MAPK inhibitor (SB203580), or in control medium. Cells were harvested at 3, 6, 24 and 48 hours after incubation. The cell count, trans-epithelial electrical resistance (TER) , macromolecular permeability (fluorescence staining), and proteomics were measured at different time points.


RESULTS
Compared with control group,the amount of airway epithelial cells in LPS group was significantly lowered at 24 hours and 48 hours [24 hours: (62.5 ± 12.0)% vs. (85.0 ± 15.0)% , 1'=-5.681, P=0.001 ; 48 hours: (67.5 ± 17.0)% vs. (79.0 ± 20.0)% , 1'=-4.260,P=0.00 1 J, TER was also significantly decreased at 3 hours and 48 hours (D/cm2 , 3 hours: 307 ± 108 vs. 376 ± 60,1'=-3.606, P=0.049; 48 hours: 290 ± 86 vs. 371 ± 43, 1'=6.971, P=0.037), and the macromolecular permeability was shown to he increased in LPS group [48 hours: (122.2 ± 22.0)% vs. (100.0 ± 18.0)%, 1'=3.182, P=0.036]; and phosphorylation-p38MAPK p-p38MAPK) was increased (relative intensity: 0.34 ± 0.16 vs. 0.28 ± 0.10,1'=4.303, P=0.029). However, SB203580 attenuated the damages induced by LPS both in the amount of epithelial cells [24 hours: (82.5±22.0)% vs. (62.5±25.0)%, 1'=-6.124, P=0.010; 48 hours: (79.5±28.0)% vs. (67.5 ± 16.0)% , 1'=-3.860, P=0.039 J, and TER of epithelial cells (Diem', 48 hours: 411 ± 118 vs. 290 ± 97,1'=3.560, P=0.022) . In addition, the down-regulation of expression of p-p38MAPK as induced hy LPS was significantly alleviate by SB203580 (relative intensity: 0.04 ±0.01 vs. 0.34 ±0.16, 1'=3.840; P=0.011).


CONCLUSIONS
LPS induced airway epithelial barrier dysfunction in ARDS, and p38MAPK may be involved in the pathway of LPS induced airway epithelial barrier dysfunction.
Jie
J
Ma
Bin
B
Ouyang
Jian-bo
JB
Lai
Xiang-dong
XD
Guan
D002470:Cell Survival; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D012128:Respiratory Distress Syndrome / Q000378:metabolism* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D048051:p38 Mitogen-Activated Protein Kinases