PMID- 32098061
OWN - NLM
STAT- MEDLINE
DCOM- 20201119
LR  - 20211204
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 4
DP  - 2020 Feb 21
TI  - Biapenem as a Novel Insight into Drug Repositioning against Particulate 
      Matter-Induced Lung Injury.
LID - 10.3390/ijms21041462 [doi]
LID - 1462
AB  - The screening of biologically active chemical compound libraries can be an 
      efficient way to reposition Food and Drug Adminstration (FDA)-approved drugs or 
      to discover new therapies for human diseases. Particulate matter with an 
      aerodynamic 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. This study 
      illustrates drug repositioning with biapenem (BIPM) for the modulation of 
      PM-induced lung injury. Biapenem was used for the treatment of severe infections. 
      Mice were treated with BIPM via tail-vein injection after the intratracheal 
      instillation of PM(2.5). Alterations in the lung wet/dry weight, total 
      protein/total cell count and lymphocyte count, inflammatory cytokines in the 
      bronchoalveolar lavage fluid (BALF), vascular permeability, and histology were 
      monitored in the PM(2.5)-treated mice. BIPM effectively reduced the pathological 
      lung injury, lung wet/dry weight ratio, and hyperpermeability caused by PM(2.5). 
      Enhanced myeloperoxidase (MPO) activity by PM(2.5) in the pulmonary tissue was 
      inhibited by BIPM. Moreover, increased levels of inflammatory cytokines and total 
      protein by PM(2.5) in the BALF were also decreased by BIPM treatment. In 
      addition, BIPM markedly suppressed PM(2.5)-induced increases in the number of 
      lymphocytes in the BALF. Additionally, the activity of mammalian target of 
      rapamycin (mTOR) was increased by BIPM. Administration of PM(2.5) increased the 
      expression levels of toll-like receptor 4 (TLR4), MyD88, and the 
      autophagy-related proteins LC3 II and Beclin 1, which were suppressed by BIPM. In 
      conclusion, these findings indicate that BIPM 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 pulmonary injury.
FAU - Lee, Wonhwa
AU  - Lee W
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, Korea.
FAU - Baek, Moon-Chang
AU  - Baek MC
AD  - Department of Molecular Medicine, CMRI, School of Medicine, Kyungpook National 
      University, Daegu 41566, Korea.
FAU - Kim, Kyung-Min
AU  - Kim KM
AUID- ORCID: 0000-0003-4812-6297
AD  - Division of Plant Biosciences, School of Applied BioSciences, College of 
      Agriculture and Life Science, Kyungpook National University, Daegu 41566, Korea.
FAU - Bae, Jong-Sup
AU  - Bae JS
AUID- ORCID: 0000-0002-5756-9367
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, Korea.
LA  - eng
GR  - HI15C0001/a grant of the Korea Health Technology R&D Project through the Korea 
      Health Industry Development Institute (KHIDI), funded by the Ministry of Health & 
      Welfare, Republic of Korea/
GR  - 2017M3A9G8083382/by the National Research Foundation of Korea (NRF) grant funded 
      by the Korean government/
PT  - Journal Article
DEP - 20200221
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Beclin-1)
RN  - 0 (Becn1 protein, mouse)
RN  - 0 (Cytokines)
RN  - 0 (Map1lc3b protein, mouse)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Particulate Matter)
RN  - 0 (Thienamycins)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - YR5U3L9ZH1 (biapenem)
SB  - IM
MH  - Animals
MH  - Beclin-1/immunology
MH  - Bronchoalveolar Lavage
MH  - Cytokines/immunology
MH  - *Drug Repositioning
MH  - *Lung/immunology/pathology
MH  - *Lung Injury/chemically induced/drug therapy/immunology/pathology
MH  - Lymphocytes/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microtubule-Associated Proteins/immunology
MH  - Myeloid Differentiation Factor 88/immunology
MH  - Particulate Matter/*toxicity
MH  - TOR Serine-Threonine Kinases/immunology
MH  - Thienamycins/*pharmacology
MH  - Toll-Like Receptor 4/immunology
PMC - PMC7073049
OTO - NOTNLM
OT  - TLR4-mTOR-autophagy
OT  - biapenem
OT  - drug repositioning
OT  - lung injury
OT  - particulate matter
COIS- The authors declare no conflicts of interest.
EDAT- 2020/02/27 06:00
MHDA- 2020/11/20 06:00
PMCR- 2020/02/01
CRDT- 2020/02/27 06:00
PHST- 2020/01/29 00:00 [received]
PHST- 2020/02/15 00:00 [revised]
PHST- 2020/02/18 00:00 [accepted]
PHST- 2020/02/27 06:00 [entrez]
PHST- 2020/02/27 06:00 [pubmed]
PHST- 2020/11/20 06:00 [medline]
PHST- 2020/02/01 00:00 [pmc-release]
AID - ijms21041462 [pii]
AID - ijms-21-01462 [pii]
AID - 10.3390/ijms21041462 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Feb 21;21(4):1462. doi: 10.3390/ijms21041462.