Research Papers:
KGF2 ameliorates acute lung injury via inhibiting TH17 cellsNFκBdependent inflammation and activating the PI3K/Akt survival signaling pathway in mice
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Linlin Wang1,*, Jian Wang1,*, Shimeng Ji1, Dongni Hou1, Cuicui Chen1, Chunxue Bai1, Jian Zhou1 and Yuanlin Song1,2,3
1Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
2Shanghai Public Health Clinical Center, Shanghai 201508, China
3Zhongshan Hospital, Qingpu Branch, Fudan University, Shanghai 201700, China
*Co-author
Correspondence to:
Yuanlin Song, email: [email protected]
Jian Zhou, email: [email protected]
Chunxue Bai, email: [email protected]
Keywords: LPS induced ALI; Th17 and Treg cells; KGF-2; PI3K/Akt; NF-κB
Received: October 20, 2017 Accepted: January 03, 2018 Published: January 13, 2018
ABSTRACT
Acute lung injury is characterized by alveolar injury, inflammation, and infiltration of inflammatory cells. Although the protective effects of keratinocyte growth factor-2 on ALI have been defined, the mechanisms remain unclear. Lipopolysaccharides (Pseudomonas aeruginosa) was administered intratracheally into mice lungs, and peak lung injury occurred on day 6 after the LPS challenge, with resolution on day 10. A progressive influx of CD4+CD25+Foxp3+T cells into the lungs and spleen on day 1, which peaked on day 6, and was maintained at high level on day 10. The percentage of Th17 cells in lung tissue and blood was higher in the ALI group than in the control group, which peaked on day 2, and returned to nearly normal on day 10. KGF-2 attenuated lung injury by inhibiting the prevalence of Th17 cells through STAT3 dysfunction and NF-κB signal, and improved survival rate by activating the PI3K/Akt signal. These results illustrated a new mechanism of KGF-2 on ALI by inhibiting Th17 cells mediated by STAT3-NF-κB, and activating the PI3k/Akt signal.