Costunolide alleviates HKSA-induced acute lung injury via inhibition of macrophage activation  

作　　者：Yun-tian Chen Yao Du Bo Zhao Li-xing Gan Kai-kai Yu Lei Sun Jian Wang Feng Qian 

机构地区：[1]Department of Respiratory Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China [2]Department of Infectious Diseases, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai 200240, China [3]Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China

出　　处：《Acta Pharmacologica Sinica》2019年第8期1040-1048,共9页中国药理学报（英文版）

基　　金：supported by the National Key Research and Development Program of China (2017YFC0908500);National Natural Science Foundation of China (81773741,81573438,31741038,and 31770921)

摘　　要：Staphylococcus aureus (S. aureus) infection leads to a severe inflammatory response and causes acute lung injury (ALI), eventually threatening human life. Therefore, it is of importance to find an agent to inhibit infiammation and reduce ALI. Here, we found that costunolide, a sesquiterpene lactone, displays anti-infiammatory effects and ameliorates heat-killed S. aureus (HKSA)-induced pneumonia. Costunolide treatment attenuated HKSA-induced murine ALI in which pulmonary neutrophil infltration was inhibited, lung edema was decreased, and the production of pro-inflammatory cytokines was significantly reduced. In addition, costunolide dose-dependently inhibited the generation of IL-6, TNF-α, IL-1β, and keratinocyte-derived cytokine (KC), as well as the expression of iNOS, in HKSA-induced macrophages. Furthermore, costunolide attenuated the phosphorylation of p38 MAPK and cAMP response element-binding protein (CREB). Collectively, our findings suggested that costunolide is a promising agent for alleviating bacterial-induced ALI via the inhibition of the MAPK signaling pathways.Staphylococcus aureus(S.aureus)infection leads to a severe inflammatory response and causes acute lung injury(ALI),eventually threatening human life.Therefore,it is of importance to find an agent to inhibit inflammation and reduce ALI.Here,we found that costunolide,a sesquiterpene lactone,displays anti-inflammatory effects and ameliorates heat-killed S.aureus(HKSA)-induced pneumonia.Costunolide treatment attenuated HKSA-induced murine ALI in which pulmonary neutrophil infiltration was inhibited,lung edema was decreased,and the production of pro-inflammatory cytokines was significantly reduced.In addition,costunolide dose-dependently inhibited the generation of IL-6,TNF-α,IL-1β,and keratinocyte-derived cytokine(KC),as well as the expression of iNOS,in HKSA-induced macrophages.Furthermore,costunolide attenuated the phosphorylation of p38 MAPK and cAMP response element-binding protein(CREB).Collectively,our findings suggested that costunolide is a promising agent for alleviating bacterialinduced ALI via the inhibition of the MAPK signaling pathways.

关 键 词：COSTUNOLIDE STAPHYLOCOCCUS AUREUS PNEUMONIA MACROPHAGE MAPK signaling 

分 类 号：R[医药卫生]