3‐O‐trans‐caffeoyloleanolic acid improves acute lung injury via antiinflammation and antioxidative stress involved PI3K/AKT pathway

Author(s):  
Jianhua Huang ◽  
Xueping Nong ◽  
Yanling Chen ◽  
Aimei Zhang ◽  
Lerong Chen
2019 ◽  
Vol 99 (12) ◽  
pp. 1795-1809 ◽  
Author(s):  
Jia Shi ◽  
Jianbo Yu ◽  
Yuan Zhang ◽  
Lili Wu ◽  
Shuan Dong ◽  
...  

Author(s):  
Xudong Wang ◽  
Chao Zhang ◽  
Chao Chen ◽  
Yi Guo ◽  
Xiaoyan Meng ◽  
...  

2012 ◽  
Vol 13 (1) ◽  
pp. 29 ◽  
Author(s):  
Wang Deng ◽  
Chang- Yi Li ◽  
Jin Tong ◽  
Wei Zhang ◽  
Dao-Xin Wang

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Yi Yang ◽  
Yang Cheng ◽  
Qing-Quan Lian ◽  
Li Yang ◽  
Wei Qi ◽  
...  

The lipoxins are the first proresolution mediators to be recognized and described as the endogenous “braking signals” for inflammation. We evaluated the anti-inflammatory and proresolution bioactions of lipoxin A4in our lipopolysaccharide (LPS-)induced lung injury model. We demonstrated that lipoxin A4significantly improved histology of rat lungs and inhibited IL-6 and TNF-αin LPS-induced lung injury. In addition, lipoxin A4increased alveolar fluid clearance (AFC) and the effect of lipoxin A4on AFC was abolished byCFTRinh-172(a specific inhibitor of CFTR). Moreover, lipoxin A4could increase cystic fibrosis transmembrane conductance regulator (CFTR) protein expressionin vitroandin vivo. In rat primary alveolar type II (ATII) cells, LPS decreased CFTR protein expression via activation of PI3K/Akt, and lipoxin A4suppressed LPS-stimulated phosphorylation of Akt. These results showed that lipoxin A4enhanced CFTR protein expression and increased AFC via PI3K/Akt pathway. Thus, lipoxin A4may provide a potential therapeutic approach for acute lung injury.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhonghua Lu ◽  
Wei Chang ◽  
Shanshan Meng ◽  
Xiuping Xu ◽  
Jianfeng Xie ◽  
...  

Abstract Background Mesenchymal stem cells (MSCs) have been shown to alleviate acute lung injury (ALI) via paracrine hepatocyte growth factor (HGF) and to induce the differentiation of dendritic cells (DCs) into tolerogenic dendritic cells (DCregs) and participate in the immune response. However, whether MSCs induce the production of DCregs by secreting HGF to alleviate early ALI remains unclear. We observed that the protective effect of mouse bone marrow-derived MSCs against lipopolysaccharide (LPS)-induced ALI was achieved by inducing mature DCs (mDCs) to differentiate into DCregs, and its mechanism is related to the activation of the HGF/Akt pathway. Methods MSCs or MSCs with overexpression or knockdown of HGF were cocultured with DCs derived from mouse bone marrow using a Transwell system for 3 days. Moreover, we used MSCs or MSCs with overexpression or knockdown of HGF to treat LPS-induced ALI mice for 24 h. Flow cytometry was performed to measure the phagocytosis, accumulation, and maturation of DCs, as well as proliferation of T cells. Lung injury was estimated by lung wet weight to body weight ratio (LWW/BW) and histopathological analysis. Furthermore, we used the Akt inhibitor MK-2206 in a coculture system to elucidate the role of the HGF/Akt pathway in regulating the differentiation of DCs into regulatory DCs and relieving lung injury in early ALI mice. Results Immature DCs (imDCs) were induced to mature after 24 h of LPS (50 ng/ml) stimulation. MSCs or HGF induced the differentiation of mDCs into regulatory DCs characterized by low expression of MHCII, CD86, and CD40 molecules, strong phagocytic function, and the ability to inhibit T cell proliferation. The effect of MSCs on DCregs was enhanced with the increase in HGF secretion and was weakened with the decrease in HGF secretion. DCregs induced by recombinant HGF were attenuated by the Akt inhibitor MK-2206. Lung DC aggregation and mDC ratio increased in LPS-induced ALI mice, while treatment with MSCs decreased lung DC aggregation and maturation and alleviated lung pathological injury. High expression of the HGF gene enhanced the above effect of MSCs, while decreased expression of HGF weakened the above effect of MSCs. Conclusions MSCs alleviate early ALI via paracrine HGF by inducing mDCs to differentiate into regulatory DCs. Furthermore, the mechanism of HGF-induced differentiation of mDCs into DCregs is related to the activation of the Akt pathway.


2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Zhiling Fu ◽  
Ze Zhang ◽  
Xiuying Wu ◽  
Jin Zhang

Background. Hydrogen-rich saline (HRS) has strong anti-inflammatory, antioxidative stress, and antiapoptotic properties. The study focused on the protection of HRS on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rat models and the relationship with autophagic regulation and mTOR/TFEB signaling pathway. Material and Methods. The LPS-induced ALI rats’ model was established. Pathohistological change in lung tissue was detected by hematoxylin-eosin staining. The inflammatory cytokines were examined by enzyme-linked immunosorbent assay (ELISA). The key apoptosis proteins and autophagy-relevant proteins were analyzed by western blotting. In vitro, HPMEC models of ALI were treated with LPS. The inflammatory cytokines were detected. Apoptosis rate was determined by flow cytometry. The autophagy and mTOR/TFEB signaling pathway-related proteins were detected by western blot and immunohistochemical staining. Results. HRS attenuated LPS-induced ALI and apoptosis both in vivo and in vitro. HRS attenuated inflammatory response, inhibited apoptosis, induced and activated autophagy in LPS-induced ALI model, and downregulated mTOR/TFEB signaling pathway. The protection of HRS can be blocked by autophagy inhibitor. Moreover, mTOR activator reversed HRS protection and mTOR inhibitor enhanced HRS protection in LPS-induced model and HRS activated autophagy via mTOR/TFEB signaling pathway. Conclusion. The results confirmed the protection of HRS in LPS-induced ALI by regulating apoptosis through inhibiting the mTOR/TFEB signaling pathway.


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