| Autor: |
Ding YH; Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China., Song YD; Department of Clinical Laboratory, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China., Wu YX; Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China., He HQ; Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China., Yu TH; Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China., Hu YD; Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China., Zhang DP; Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China., Jiang HC; Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China., Yu KK; Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China., Li XZ; Department of Clinical Laboratory, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China., Sun L; Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China., Qian F; Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China. fengqian@sjtu.edu.cn.; Research Center for Cancer Precision Medicine, Department of Medical Oncology, Bengbu Medical College, Bengbu, 233003, China. fengqian@sjtu.edu.cn.; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, 221004, China. fengqian@sjtu.edu.cn. |
| Abstrakt: |
Isoalantolactone (IAL) is a sesquiterpene lactone extracted from roots of Inula helenium L and has shown anti-inflammatory effects. In this study we investigated the therapeutic effects of IAL on acute lung injury (ALI) and elucidated the mechanisms underlying its anti-inflammation potential in vitro and in vivo. Treatment with lipopolysaccharide (LPS, 100 ng/mL) drastically stimulated production of inflammatory mediators such as NO, TNF-α, IL-1β, and IL-6 in mouse bone marrow-derived macrophages (BMDMs), which was dose-dependently suppressed by pretreatment with IAL (2.5, 5, 10, 20 μM). We further revealed that IAL suppressed LPS-induced NF-κB, ERK, and Akt activation. Moreover, the downregulation of non-degradable K63-linked polyubiquitination of TRAF6, an upstream transcription factor of NF-κB, contributed to the anti-inflammatory effects of IAL. ALI was induced in mice by intratracheal injection of LPS (5 mg/kg). Administration of IAL (20 mg/kg, i.p.) significantly suppressed pulmonary pathological changes, neutrophil infiltration, pulmonary permeability, and pro-inflammatory cytokine expression. Our results demonstrate that IAL is a potential therapeutic reagent against inflammation and ALI. |
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