PMID- 31669889 OWN - NLM STAT- MEDLINE DCOM- 20200417 LR - 20200417 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 77 DP - 2019 Dec TI - Protostemonine alleviates heat-killed methicillin-resistant Staphylococcus aureus-induced acute lung injury through MAPK and NF-kappaB signaling pathways. PG - 105964 LID - S1567-5769(19)31836-3 [pii] LID - 10.1016/j.intimp.2019.105964 [doi] AB - Acute lung injury (ALI) and its most severe form acute respiratory distress syndrome (ARDS) caused by gram-positive bacteria threatens human life because effective treatments and medicines is unavailable. Protostemonine (PSN), an active alkaloid mainly isolated from the roots of Stemona sesslifolia, has anti-inflammatory effects on asthma and gram-negative bacteria-induced ALI. Here, we found that PSN exhibits anti-inflammatory effects and alleviates heat-killed methicillin-resistant Staphylococcus aureus (HKMRSA)-induced pneumonia. PSN treatment significantly attenuated HKMRSA-induced pathological injury, pulmonary neutrophil infiltration, tissue permeability and the production of pro-inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) in murine ALI model. In addition, PSN decreased the content of TNF-alpha, IL-1beta, IL-6 and the expression of iNOS, as well as the production of NO in HKMRSA-induced bone marrow derived macrophages (BMDMs). Furthermore, treatment with PSN suppressed the activation of MAPKs (e.g. p38 MAPK, JNK and ERK) and NF-kappaB. Collectively, our results suggest that PSN ameliorates gram-positive bacteria-induced ALI in mice by inhibition of the MAPK and NF-kappaB signaling pathways, and our studies suggest that PSN might be a novel candidate for treating ALI/ARDS. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Wu, Yaxian AU - Wu Y AD - Wuxi School of Medicine, Jiangnan University, 1800 Lihu Avenue, Wuxi 214122, PR China. FAU - Nie, Yunjuan AU - Nie Y AD - Wuxi School of Medicine, Jiangnan University, 1800 Lihu Avenue, Wuxi 214122, PR China. FAU - Huang, Jianfeng AU - Huang J AD - Department of Radiation Oncology, Affiliated Hospital of Jiangnan University, Wuxi 214062, PR China. FAU - Qiu, Yubao AU - Qiu Y AD - Wuxi School of Medicine, Jiangnan University, 1800 Lihu Avenue, Wuxi 214122, PR China. FAU - Wan, Binbin AU - Wan B AD - Wuxi School of Medicine, Jiangnan University, 1800 Lihu Avenue, Wuxi 214122, PR China. FAU - Liu, Gang AU - Liu G AD - Wuxi School of Medicine, Jiangnan University, 1800 Lihu Avenue, Wuxi 214122, PR China. FAU - Chen, Junliang AU - Chen J AD - Wuxi School of Medicine, Jiangnan University, 1800 Lihu Avenue, Wuxi 214122, PR China. FAU - Chen, Dan AU - Chen D AD - Wuxi School of Medicine, Jiangnan University, 1800 Lihu Avenue, Wuxi 214122, PR China; State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China. Electronic address: danchen09@163.com. FAU - Pang, Qingfeng AU - Pang Q AD - Wuxi School of Medicine, Jiangnan University, 1800 Lihu Avenue, Wuxi 214122, PR China. Electronic address: qfpang@jiangnan.edu.cn. LA - eng PT - Journal Article DEP - 20191024 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cytokines) RN - 0 (NF-kappa B) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Acute Lung Injury/*drug therapy/metabolism/microbiology MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Cytokines/metabolism MH - Hot Temperature MH - Inflammation/drug therapy/metabolism/microbiology MH - Lung/drug effects/metabolism/microbiology MH - Macrophages/drug effects/microbiology MH - Male MH - Methicillin-Resistant Staphylococcus aureus/*drug effects MH - Mice MH - Mice, Inbred C57BL MH - Mitogen-Activated Protein Kinases/*metabolism MH - NF-kappa B/*metabolism MH - Neutrophil Infiltration/drug effects MH - Pneumonia/drug therapy/metabolism/microbiology MH - Signal Transduction/*drug effects MH - Staphylococcal Infections/drug therapy/metabolism/microbiology MH - Stemonaceae/chemistry OTO - NOTNLM OT - Acute lung injury OT - MAPK OT - MRSA OT - Macrophage OT - NF-kappaB OT - Protostemonine EDAT- 2019/11/02 06:00 MHDA- 2020/04/18 06:00 CRDT- 2019/11/01 06:00 PHST- 2019/08/18 00:00 [received] PHST- 2019/09/27 00:00 [revised] PHST- 2019/10/03 00:00 [accepted] PHST- 2019/11/02 06:00 [pubmed] PHST- 2020/04/18 06:00 [medline] PHST- 2019/11/01 06:00 [entrez] AID - S1567-5769(19)31836-3 [pii] AID - 10.1016/j.intimp.2019.105964 [doi] PST - ppublish SO - Int Immunopharmacol. 2019 Dec;77:105964. doi: 10.1016/j.intimp.2019.105964. Epub 2019 Oct 24.