PMID- 29991449 OWN - NLM STAT- MEDLINE DCOM- 20190404 LR - 20211204 IS - 1873-2968 (Electronic) IS - 0006-2952 (Linking) VI - 155 DP - 2018 Sep TI - Protostemonine attenuates alternatively activated macrophage and DRA-induced asthmatic inflammation. PG - 198-206 LID - S0006-2952(18)30259-4 [pii] LID - 10.1016/j.bcp.2018.07.003 [doi] AB - Asthma is one of the most common pulmonary diseases that threatens human life because of lack of effective medicines. Protostemonine (PSN), an active alkaloid extracted from the roots of Stemona sesslifolia, has anti-inflammatory effects on acute lung injury and acute liver failure. However, it has not been defined whether PSN alleviates asthmatic inflammation. Here, we reported that PSN inhibits pulmonary eosinophil infiltration, goblet cell hyperplasia, mucus secretion, IgE and Th2 cytokine (IL-4, IL-5, IL-13 and IL-33) production by using DRA (dust mites, ragweed and aspergillus)-induced murine asthma model. Moreover, PSN also attenuated the expression of Arginase-1 (Arg-1), Ym-1 and Fizz-1, markers of AAM (alternatively activated macrophage) polarization, in lung tissues. In addition, PSN attenuated IL-4-induced expression of Arg-1, Ym-1 and Fizz-1 in bone marrow derived macrophages (BMDMs). Treatment with PSN decreased IL-4-induced STAT6 phosphorylation, KLF4 and IRF4 expression in BMDMs. Collectively, our results indicated that PSN ameliorates AAM polarization and asthmatic inflammation and might be a potential agent for treating asthma. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Song, Yunduan AU - Song Y AD - Department of Clinical Laboratory, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, PR China. FAU - Wu, Yaxian AU - Wu Y AD - Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China. Electronic address: yaxianwu@sjtu.edu.cn. FAU - Li, Xiaozong AU - Li X AD - Department of Clinical Laboratory, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, PR China. FAU - Shen, Yao AU - Shen Y AD - Department of Respiratory Medicine, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, PR China. FAU - Ding, Yunhe AU - Ding Y AD - Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China. Electronic address: yhding1993@sjtu.edu.cn. FAU - Zhu, Hongbo AU - Zhu H AD - Department of Pathology, Shanghai Pudong Hospital, Fudan University ,Shanghai 201399, PR China. FAU - Liu, Fangfang AU - Liu F AD - Department of Clinical Laboratory, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, PR China. FAU - Yu, Kaikai AU - Yu K AD - Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China. FAU - Sun, Lei AU - Sun L AD - Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China. Electronic address: sunlei_vicky@sjtu.edu.cn. FAU - Qian, Feng AU - Qian F AD - Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China; Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, Anhui Province 233003, PR China. Electronic address: fengqian@sjtu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180702 PL - England TA - Biochem Pharmacol JT - Biochemical pharmacology JID - 0101032 RN - 0 (KLF4 protein, human) RN - 0 (Klf4 protein, mouse) RN - 0 (Kruppel-Like Factor 4) RN - 0 (Plant Extracts) SB - IM MH - Ambrosia/*adverse effects MH - Animals MH - *Aspergillus fumigatus MH - Asthma/chemically induced/*drug therapy/metabolism MH - Cell Survival/drug effects/physiology MH - Dose-Response Relationship, Drug MH - Inflammation/chemically induced/drug therapy/metabolism MH - Kruppel-Like Factor 4 MH - Macrophages/*drug effects/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Plant Extracts/isolation & purification/pharmacology/*therapeutic use MH - *Pyroglyphidae MH - Random Allocation MH - Stemonaceae OTO - NOTNLM OT - Alternatively activated macrophage OT - Asthmatic inflammation OT - IL-4 OT - PSN OT - STAT6 EDAT- 2018/07/12 06:00 MHDA- 2019/04/05 06:00 CRDT- 2018/07/12 06:00 PHST- 2018/05/08 00:00 [received] PHST- 2018/07/01 00:00 [accepted] PHST- 2018/07/12 06:00 [pubmed] PHST- 2019/04/05 06:00 [medline] PHST- 2018/07/12 06:00 [entrez] AID - S0006-2952(18)30259-4 [pii] AID - 10.1016/j.bcp.2018.07.003 [doi] PST - ppublish SO - Biochem Pharmacol. 2018 Sep;155:198-206. doi: 10.1016/j.bcp.2018.07.003. Epub 2018 Jul 2.