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Critical Care: Critical Care: ARDS/ALI |

p38MAPK Inhibitor Ameliorates Lipopolysaccharide-Induced Mild Acute Respiratory Distress Syndrome Through Regulating the Balance of Treg Cells and Th17 Cells FREE TO VIEW

Jingjing Feng; Jindong Shi; Shanqun Li; Zhijun Jie, PhD
Author and Funding Information

The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(4_S):A158. doi:10.1016/j.chest.2016.02.164
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SESSION TITLE: Critical Care: ARDS/ALI

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: p38MAPK, a mitogen-activated protein kinase, plays a negative regulating role in the pathogenesis of acute respiratory distress syndrome (ARDS) induced by lipopolysaccharide (LPS). A p38MAPK inhibitor has previously been shown to alleviate inflammatory reaction. We recently proposed that the balance of T helper17 (Th17) and Treg cells regulated in this inflammatory conditions. In the present study, we investigated in vivo the effect of Th17/Treg balance on p38MAPK inhibitor relieved mild ARDS induced by LPS.

METHODS: KM mice received SB203580 (0.5 and 5 mg/kg) intraperitoneally 1 h prior to the intratracheal instillation of lipopolysaccharide (LPS) challenge. All mice were killed on 12h respectively. Transcript expression of FOXP3 and RORrt was detected by real-time polymerase chain reaction; IL-6, IL-10, IL-17, IL-23, and transforming growth factor (TGF-b) in Lung tissue and IL-6, TNF-a in serum were measured by enzyme-linked immunosorbent assay. The Th17 and Treg subset distribution in Lung bronchial lymph nodes was determined by flow cytometry. We also investigated histopathological conditions in Lung tissue.

RESULTS: In a LPS-induced ARDS mouse model, we found that the IL-6 and TNF-α protein concentration in the serum were lower in pretreatmenting with SB203580 groups and the production of inflammatory cytokines associate with Th17, including interleukin-17 (IL-17), IL-23, RORrt, and TGF-β was inhibited, and the production of cytokines associate with Treg, such as IL-10 and FOXP3 in Lung tissue was increased. In addition, histopathological examination indicates that SB203580 significantly attenuated tissue injury of the lungs in LPS-induced ALI. Furthermore, SB203580 also inhibited the production of Th17 cells and improved the production of Tregs in Lung bronchial lymph nodes. And the changes of cytokines had concentration dependence with SB203580

CONCLUSIONS: These results suggest that p38MAPK plays a protective effect in a LPS-induced ARDS mice model via regulating Th17/Treg balance.

CLINICAL IMPLICATIONS: Our results further clarified the pathogenic mechanism of acute respiratory distress syndrome (ARDS) induced by lipopolysaccharide (LPS), and provided a novel basis for clinical treatment of ARDS

DISCLOSURE: Jingjing Feng: University grant monies: Natural Science Foundation of Minhang District of Shanghai of China (No. 2010MHZ018), University grant monies: Young Scholars foundation of Shanghai Municipal Health Bureau (No. 2010Y036) Jindong Shi: University grant monies: Natural Science Foundation of Minhang District of Shanghai of China (No. 2010MHZ018), University grant monies: Young Scholars foundation of Shanghai Municipal Health Bureau (No. 2010Y036) Shanqun Li: University grant monies: Natural Science Foundation of Minhang District of Shanghai of China (No. 2010MHZ018), University grant monies: Young Scholars foundation of Shanghai Municipal Health Bureau (No. 2010Y036) Zhijun Jie: University grant monies: Natural Science Foundation of Minhang District of Shanghai of China (No. 2010MHZ018), University grant monies: Young Scholars foundation of Shanghai Municipal Health Bureau (No. 2010Y036)

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