PMID- 32058145 OWN - NLM STAT- MEDLINE DCOM- 20200911 LR - 20211204 IS - 1096-0953 (Electronic) IS - 0013-9351 (Linking) VI - 183 DP - 2020 Apr TI - Inhibitory functions of maslinic acid on particulate matter-induced lung injury through TLR4-mTOR-autophagy pathways. PG - 109230 LID - S0013-9351(20)30122-5 [pii] LID - 10.1016/j.envres.2020.109230 [doi] AB - Particulate matter (PM), the collection of all liquid and solid particles suspended in air, includes both organic and inorganic particles, many of which are health-hazards. PM particles with a diameter equal to or less than 2.5 mum (PM(2.5)) is a form of air pollutant that causes significant lung damage when inhaled. Maslinic acid (MA) prevents oxidative stress and pro-inflammatory cytokine generation, but there is little information available regarding its role in PM-induced lung injury. Therefore, the purpose of this study was to determine the protective activity of MA against PM(2.5)-induced lung injury. The mice were divided into seven groups (n = 10 each): a mock control group, an MA control (0.8 mg/kg mouse body weight) group, an opted PM(2.5) produced from diesel (10 mg/kg mouse body weight) group, a diesel PM(2.5)+MA (0.2, 0.4, 0.6, and 0.8 mg/kg mouse body weight) groups. Mice were treated with MA via tail-vein injection 30 min after the intratracheal instillation of a diesel PM(2.5). Changes in the wet/dry weight ratio of the lung tissue, total protein/total cell and lymphocyte counts, inflammatory cytokines in the bronchoalveolar lavage fluid (BALF), vascular permeability, and histology were monitored in diesel PM(2.5)-treated mice. The results showed that MA reduced pathological lung injury, the wet/dry weight ratio of the lung tissue, and hyperpermeability caused by diesel PM(2.5). MA also inhibited diesel PM(2.5)-induced myeloperoxidase (MPO) activity in the lung tissue, decreased the levels of diesel PM(2.5)-induced inflammatory cytokines, including tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, reduced nitric oxide (NO) and total protein in the BALF, and effectively attenuated diesel PM(2.5)-induced increases in the number of lymphocytes in the BALF. In addition, MA increased the protein phosphorylation of the mammalian target of rapamycin (mTOR) and dramatically suppressed diesel PM(2.5)-stimulated expression of toll-like receptor 4 (TLR4), MyD88, and the autophagy-related proteins LC3 II and Beclin 1. In conclusion, these findings indicate that MA has a critical anti-inflammatory effect due to its ability to regulate both the TLR4-MyD88 and mTOR-autophagy pathways and may thus be a potential therapeutic agent against diesel PM(2.5)-induced lung injury. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Jeong, So Yeon AU - Jeong SY AD - College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu, 41566, Republic of Korea. FAU - Kim, Jaehong AU - Kim J AD - Department of Biochemistry, College of Medicine, Gachon University, Incheon, 21999, Republic of Korea. FAU - Park, Eui Kyun AU - Park EK AD - Department of Pathology and Regenerative Medicine, School of Dentistry, Kyungpook National University, Daegu, 41940, Republic of Korea. FAU - Baek, Moon-Chang AU - Baek MC AD - Department of Molecular Medicine, CMRI, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea. FAU - Bae, Jong-Sup AU - Bae JS AD - College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu, 41566, Republic of Korea. Electronic address: baejs@knu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200205 PL - Netherlands TA - Environ Res JT - Environmental research JID - 0147621 RN - 0 (Cytokines) RN - 0 (Particulate Matter) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 4) RN - 0 (Triterpenes) RN - E233J88OHQ (maslinic acid) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - *Autophagy MH - Bronchoalveolar Lavage Fluid MH - Cytokines MH - Lung/drug effects MH - *Lung Injury MH - Mice MH - *Particulate Matter/toxicity MH - *Signal Transduction/drug effects MH - *TOR Serine-Threonine Kinases/drug effects MH - *Toll-Like Receptor 4/drug effects MH - *Triterpenes/pharmacology OTO - NOTNLM OT - Lung injury OT - Maslinic acid OT - Particulate matter OT - TLR4-mTOR-autophagy COIS- Declaration of competing interest The authors declare no conflicts of interest. EDAT- 2020/02/15 06:00 MHDA- 2020/09/12 06:00 CRDT- 2020/02/15 06:00 PHST- 2019/12/15 00:00 [received] PHST- 2020/01/30 00:00 [revised] PHST- 2020/02/04 00:00 [accepted] PHST- 2020/02/15 06:00 [pubmed] PHST- 2020/09/12 06:00 [medline] PHST- 2020/02/15 06:00 [entrez] AID - S0013-9351(20)30122-5 [pii] AID - 10.1016/j.envres.2020.109230 [doi] PST - ppublish SO - Environ Res. 2020 Apr;183:109230. doi: 10.1016/j.envres.2020.109230. Epub 2020 Feb 5.