Dehydrocostus Lactone Attenuates Methicillin-Resistant <i>Staphylococcus aureus</i>-Induced Inflammation and Acute Lung Injury via Modulating Macrophage Polarization
Dehydrocostus lactone (DHL), a natural sesquiterpene lactone isolated from the traditional Chinese herbs <i>Saussurea lappa</i> and <i>Inula helenium</i> L., has important anti-inflammatory properties used for treating colitis, fibrosis, and Gram-negative bacteria-induced acu...
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doaj-c700dc77a0224279bebd1fb886cc95d22021-09-26T00:22:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-01229754975410.3390/ijms22189754Dehydrocostus Lactone Attenuates Methicillin-Resistant <i>Staphylococcus aureus</i>-Induced Inflammation and Acute Lung Injury via Modulating Macrophage PolarizationYa-Xian Wu0Feng-Juan Jiang1Gang Liu2Ying-Ying Wang3Zhi-Qi Gao4Si-Hao Jin5Yun-Juan Nie6Dan Chen7Jun-Liang Chen8Qing-Feng Pang9Wuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaWuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaDehydrocostus lactone (DHL), a natural sesquiterpene lactone isolated from the traditional Chinese herbs <i>Saussurea lappa</i> and <i>Inula helenium</i> L., has important anti-inflammatory properties used for treating colitis, fibrosis, and Gram-negative bacteria-induced acute lung injury (ALI). However, the effects of DHL on Gram-positive bacteria-induced macrophage activation and ALI remains unclear. In this study, we found that DHL inhibited the phosphorylation of p38 MAPK, the degradation of IκBα, and the activation and nuclear translocation of NF-κB p65, but enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of Nrf2 and HO-1 in lipoteichoic acid (LTA)-stimulated RAW264.7 cells and primary bone-marrow-derived macrophages (BMDMs). Given the critical role of the p38 MAPK/NF-κB and AMPK/Nrf2 signaling pathways in the balance of M1/M2 macrophage polarization and inflammation, we speculated that DHL would also have an effect on macrophage polarization. Further studies verified that DHL promoted M2 macrophage polarization and reduced M1 polarization, then resulted in a decreased inflammatory response. An in vivo study also revealed that DHL exhibited anti-inflammatory effects and ameliorated methicillin-resistant <i>Staphylococcus aureus</i> (MRSA)-induced ALI. In addition, DHL treatment significantly inhibited the p38 MAPK/NF-κB pathway and activated AMPK/Nrf2 signaling, leading to accelerated switching of macrophages from M1 to M2 in the MRSA-induced murine ALI model. Collectively, these data demonstrated that DHL can promote macrophage polarization to an anti-inflammatory M2 phenotype via interfering in p38 MAPK/NF-κB signaling, as well as activating the AMPK/Nrf2 pathway in vitro and in vivo. Our results suggested that DHL might be a novel candidate for treating inflammatory diseases caused by Gram-positive bacteria.https://www.mdpi.com/1422-0067/22/18/9754Dehydrocostus lactoneLTAMRSAacute lung injurymacrophage polarization |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ya-Xian Wu Feng-Juan Jiang Gang Liu Ying-Ying Wang Zhi-Qi Gao Si-Hao Jin Yun-Juan Nie Dan Chen Jun-Liang Chen Qing-Feng Pang |
spellingShingle |
Ya-Xian Wu Feng-Juan Jiang Gang Liu Ying-Ying Wang Zhi-Qi Gao Si-Hao Jin Yun-Juan Nie Dan Chen Jun-Liang Chen Qing-Feng Pang Dehydrocostus Lactone Attenuates Methicillin-Resistant <i>Staphylococcus aureus</i>-Induced Inflammation and Acute Lung Injury via Modulating Macrophage Polarization International Journal of Molecular Sciences Dehydrocostus lactone LTA MRSA acute lung injury macrophage polarization |
author_facet |
Ya-Xian Wu Feng-Juan Jiang Gang Liu Ying-Ying Wang Zhi-Qi Gao Si-Hao Jin Yun-Juan Nie Dan Chen Jun-Liang Chen Qing-Feng Pang |
author_sort |
Ya-Xian Wu |
title |
Dehydrocostus Lactone Attenuates Methicillin-Resistant <i>Staphylococcus aureus</i>-Induced Inflammation and Acute Lung Injury via Modulating Macrophage Polarization |
title_short |
Dehydrocostus Lactone Attenuates Methicillin-Resistant <i>Staphylococcus aureus</i>-Induced Inflammation and Acute Lung Injury via Modulating Macrophage Polarization |
title_full |
Dehydrocostus Lactone Attenuates Methicillin-Resistant <i>Staphylococcus aureus</i>-Induced Inflammation and Acute Lung Injury via Modulating Macrophage Polarization |
title_fullStr |
Dehydrocostus Lactone Attenuates Methicillin-Resistant <i>Staphylococcus aureus</i>-Induced Inflammation and Acute Lung Injury via Modulating Macrophage Polarization |
title_full_unstemmed |
Dehydrocostus Lactone Attenuates Methicillin-Resistant <i>Staphylococcus aureus</i>-Induced Inflammation and Acute Lung Injury via Modulating Macrophage Polarization |
title_sort |
dehydrocostus lactone attenuates methicillin-resistant <i>staphylococcus aureus</i>-induced inflammation and acute lung injury via modulating macrophage polarization |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-09-01 |
description |
Dehydrocostus lactone (DHL), a natural sesquiterpene lactone isolated from the traditional Chinese herbs <i>Saussurea lappa</i> and <i>Inula helenium</i> L., has important anti-inflammatory properties used for treating colitis, fibrosis, and Gram-negative bacteria-induced acute lung injury (ALI). However, the effects of DHL on Gram-positive bacteria-induced macrophage activation and ALI remains unclear. In this study, we found that DHL inhibited the phosphorylation of p38 MAPK, the degradation of IκBα, and the activation and nuclear translocation of NF-κB p65, but enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of Nrf2 and HO-1 in lipoteichoic acid (LTA)-stimulated RAW264.7 cells and primary bone-marrow-derived macrophages (BMDMs). Given the critical role of the p38 MAPK/NF-κB and AMPK/Nrf2 signaling pathways in the balance of M1/M2 macrophage polarization and inflammation, we speculated that DHL would also have an effect on macrophage polarization. Further studies verified that DHL promoted M2 macrophage polarization and reduced M1 polarization, then resulted in a decreased inflammatory response. An in vivo study also revealed that DHL exhibited anti-inflammatory effects and ameliorated methicillin-resistant <i>Staphylococcus aureus</i> (MRSA)-induced ALI. In addition, DHL treatment significantly inhibited the p38 MAPK/NF-κB pathway and activated AMPK/Nrf2 signaling, leading to accelerated switching of macrophages from M1 to M2 in the MRSA-induced murine ALI model. Collectively, these data demonstrated that DHL can promote macrophage polarization to an anti-inflammatory M2 phenotype via interfering in p38 MAPK/NF-κB signaling, as well as activating the AMPK/Nrf2 pathway in vitro and in vivo. Our results suggested that DHL might be a novel candidate for treating inflammatory diseases caused by Gram-positive bacteria. |
topic |
Dehydrocostus lactone LTA MRSA acute lung injury macrophage polarization |
url |
https://www.mdpi.com/1422-0067/22/18/9754 |
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