PMID- 32155958
OWN - NLM
STAT- MEDLINE
DCOM- 20210311
LR  - 20210311
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 9
IP  - 3
DP  - 2020 Mar 6
TI  - The Peroxisome Proliferator-Activated Receptor alpha- Agonist Gemfibrozil Promotes 
      Defense Against Mycobacterium abscessus Infections.
LID - 10.3390/cells9030648 [doi]
LID - 648
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) shows promising potential to 
      enhance host defenses against Mycobacterium tuberculosis infection. Herein we 
      evaluated the protective effect of PPARalpha against nontuberculous mycobacterial 
      (NTM) infections. Using a rapidly growing NTM species, Mycobacterium abscessus 
      (Mabc), we found that the intracellular bacterial load and histopathological 
      damage were increased in PPARalpha-null mice in vivo. In addition, PPARalpha deficiency 
      led to excessive production of proinflammatory cytokines and chemokines after 
      infection of the lung and macrophages. Notably, administration of gemfibrozil 
      (GEM), a PPARalpha activator, significantly reduced the in vivo Mabc load and 
      inflammatory response in mice. Transcription factor EB was required for the 
      antimicrobial response against Mabc infection. Collectively, these results 
      suggest that manipulation of PPARalpha activation has promising potential as a 
      therapeutic strategy for NTM disease.
FAU - Kim, Yi Sak
AU  - Kim YS
AUID- ORCID: 0000-0003-4477-0018
AD  - Department of Microbiology, Chungnam National University School of Medicine, 
      Daejeon 35015, Korea.
AD  - Infection Control Convergence Research Center, Chungnam National University 
      School of Medicine, Daejeon 35015, Korea.
FAU - Kim, Jin Kyung
AU  - Kim JK
AD  - Department of Microbiology, Chungnam National University School of Medicine, 
      Daejeon 35015, Korea.
AD  - Infection Control Convergence Research Center, Chungnam National University 
      School of Medicine, Daejeon 35015, Korea.
FAU - Hanh, Bui Thi Bich
AU  - Hanh BTB
AD  - Molecular Mechanisms of Antibiotics, Division of Life Science, Research Institute 
      of Life Science, Gyeongsang National University, Jinju 52828, Korea.
AD  - Division of Applied Life Science (BK21plus Program), Gyeongsang National 
      University, Jinju 52828, Korea.
FAU - Kim, Soo Yeon
AU  - Kim SY
AD  - Drug & Disease Target Research Team, Division of Bioconvergence Analysis, Korea 
      Basic Science Institute (KBSI), Cheongju 28119, Korea.
FAU - Kim, Hyeon Ji
AU  - Kim HJ
AD  - Department of Microbiology, Chungnam National University School of Medicine, 
      Daejeon 35015, Korea.
AD  - Infection Control Convergence Research Center, Chungnam National University 
      School of Medicine, Daejeon 35015, Korea.
FAU - Kim, Young Jae
AU  - Kim YJ
AD  - Department of Microbiology, Chungnam National University School of Medicine, 
      Daejeon 35015, Korea.
AD  - Infection Control Convergence Research Center, Chungnam National University 
      School of Medicine, Daejeon 35015, Korea.
FAU - Jeon, Sang Min
AU  - Jeon SM
AD  - Department of Microbiology, Chungnam National University School of Medicine, 
      Daejeon 35015, Korea.
AD  - Infection Control Convergence Research Center, Chungnam National University 
      School of Medicine, Daejeon 35015, Korea.
FAU - Park, Cho Rong
AU  - Park CR
AD  - Department of Microbiology, Chungnam National University School of Medicine, 
      Daejeon 35015, Korea.
AD  - Infection Control Convergence Research Center, Chungnam National University 
      School of Medicine, Daejeon 35015, Korea.
FAU - Oh, Goo Taeg
AU  - Oh GT
AD  - Department of Life Science, Ewha Womans University, Seoul 03760, Korea.
FAU - Park, June-Woo
AU  - Park JW
AUID- ORCID: 0000-0002-7235-4241
AD  - Environmental Risk Assessment Research Division, Korea Institute of Toxicology, 
      Jinju 52834, Korea.
AD  - Human and Environmental Toxicology Program, Korea University of Science and 
      Technology (UST), Daejeon 34113, Korea.
FAU - Kim, Jin-Man
AU  - Kim JM
AD  - Department of Pathology, Chungnam National University School of Medicine, Daejeon 
      35015, Korea.
FAU - Jang, Jichan
AU  - Jang J
AD  - Molecular Mechanisms of Antibiotics, Division of Life Science, Research Institute 
      of Life Science, Gyeongsang National University, Jinju 52828, Korea.
AD  - Division of Applied Life Science (BK21plus Program), Gyeongsang National 
      University, Jinju 52828, Korea.
FAU - Jo, Eun-Kyeong
AU  - Jo EK
AD  - Department of Microbiology, Chungnam National University School of Medicine, 
      Daejeon 35015, Korea.
AD  - Infection Control Convergence Research Center, Chungnam National University 
      School of Medicine, Daejeon 35015, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200306
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Hypolipidemic Agents)
RN  - 0 (PPAR alpha)
RN  - Q8X02027X3 (Gemfibrozil)
SB  - IM
MH  - Animals
MH  - Gemfibrozil/pharmacology/*therapeutic use
MH  - Humans
MH  - Hypolipidemic Agents/pharmacology/*therapeutic use
MH  - Male
MH  - Mice
MH  - Mycobacterium Infections, Nontuberculous/*drug therapy
MH  - PPAR alpha/pharmacology/*therapeutic use
PMC - PMC7140404
OTO - NOTNLM
OT  - Mycobacterium abscessus
OT  - PPARalpha
OT  - TFEB
OT  - gemfibrozil
OT  - inflammation
COIS- The authors declare no competing interests.
EDAT- 2020/03/12 06:00
MHDA- 2021/03/12 06:00
PMCR- 2020/03/01
CRDT- 2020/03/12 06:00
PHST- 2020/01/13 00:00 [received]
PHST- 2020/02/24 00:00 [revised]
PHST- 2020/03/03 00:00 [accepted]
PHST- 2020/03/12 06:00 [entrez]
PHST- 2020/03/12 06:00 [pubmed]
PHST- 2021/03/12 06:00 [medline]
PHST- 2020/03/01 00:00 [pmc-release]
AID - cells9030648 [pii]
AID - cells-09-00648 [pii]
AID - 10.3390/cells9030648 [doi]
PST - epublish
SO  - Cells. 2020 Mar 6;9(3):648. doi: 10.3390/cells9030648.