PMID- 34575918
OWN - NLM
STAT- MEDLINE
DCOM- 20211101
LR  - 20211101
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 18
DP  - 2021 Sep 9
TI  - Dehydrocostus Lactone Attenuates Methicillin-Resistant Staphylococcus 
      aureus-Induced Inflammation and Acute Lung Injury via Modulating Macrophage 
      Polarization.
LID - 10.3390/ijms22189754 [doi]
LID - 9754
AB  - Dehydrocostus lactone (DHL), a natural sesquiterpene lactone isolated from the 
      traditional Chinese herbs Saussurea lappa and Inula helenium 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 IkappaBalpha, and the activation and nuclear translocation of 
      NF-kappaB 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-kappaB 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 Staphylococcus aureus (MRSA)-induced ALI. In addition, DHL 
      treatment significantly inhibited the p38 MAPK/NF-kappaB 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-kappaB 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.
FAU - Wu, Ya-Xian
AU  - Wu YX
AD  - Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
AD  - School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
FAU - Jiang, Feng-Juan
AU  - Jiang FJ
AD  - Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
FAU - Liu, Gang
AU  - Liu G
AD  - Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
FAU - Wang, Ying-Ying
AU  - Wang YY
AD  - Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
FAU - Gao, Zhi-Qi
AU  - Gao ZQ
AD  - Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
FAU - Jin, Si-Hao
AU  - Jin SH
AD  - Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
FAU - Nie, Yun-Juan
AU  - Nie YJ
AUID- ORCID: 0000-0002-6167-4258
AD  - Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
FAU - Chen, Dan
AU  - Chen D
AD  - Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
FAU - Chen, Jun-Liang
AU  - Chen JL
AD  - Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
FAU - Pang, Qing-Feng
AU  - Pang QF
AUID- ORCID: 0000-0003-0679-4780
AD  - Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
LA  - eng
GR  - 81871518, 81901522/National Natural Science Foundation of China/
GR  - 2020M671347, 2021M691292/China Postdoctoral Science Foundation/
GR  - JUSRP11955/Fundamental Research Funds for the Central Universities/
GR  - BK20200602/Natural Science Foundation of Jiangsu Province/
PT  - Journal Article
DEP - 20210909
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Lactones)
RN  - 0 (NF-kappa B)
RN  - 0 (Sesquiterpenes)
RN  - 477-43-0 (dehydrocostus lactone)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Cell Plasticity/drug effects/immunology
MH  - Disease Models, Animal
MH  - Lactones/*pharmacology
MH  - Macrophage Activation/*drug effects/immunology
MH  - Macrophages/*drug effects/*immunology/metabolism
MH  - Methicillin-Resistant Staphylococcus aureus/*drug effects
MH  - Mice
MH  - Models, Biological
MH  - NF-kappa B/metabolism
MH  - Phosphorylation
MH  - Pneumonia, Staphylococcal/drug therapy/*etiology/metabolism/pathology
MH  - RAW 264.7 Cells
MH  - Sesquiterpenes/*pharmacology
MH  - Signal Transduction/drug effects
PMC - PMC8472345
OTO - NOTNLM
OT  - Dehydrocostus lactone
OT  - LTA
OT  - MRSA
OT  - acute lung injury
OT  - macrophage polarization
COIS- The authors declare no conflict of interest.
EDAT- 2021/09/29 06:00
MHDA- 2021/11/03 06:00
PMCR- 2021/09/09
CRDT- 2021/09/28 01:17
PHST- 2021/07/06 00:00 [received]
PHST- 2021/09/05 00:00 [revised]
PHST- 2021/09/07 00:00 [accepted]
PHST- 2021/09/28 01:17 [entrez]
PHST- 2021/09/29 06:00 [pubmed]
PHST- 2021/11/03 06:00 [medline]
PHST- 2021/09/09 00:00 [pmc-release]
AID - ijms22189754 [pii]
AID - ijms-22-09754 [pii]
AID - 10.3390/ijms22189754 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Sep 9;22(18):9754. doi: 10.3390/ijms22189754.