PMID- 29755479
OWN - NLM
STAT- MEDLINE
DCOM- 20190624
LR  - 20190624
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 9
DP  - 2018
TI  - Lysophosphatidylcholine Promotes Phagosome Maturation and Regulates Inflammatory 
      Mediator Production Through the Protein Kinase A-Phosphatidylinositol 
      3 Kinase-p38 Mitogen-Activated Protein Kinase Signaling Pathway During 
      Mycobacterium tuberculosis Infection in Mouse Macrophages.
PG  - 920
LID - 10.3389/fimmu.2018.00920 [doi]
LID - 920
AB  - Tuberculosis is caused by the infectious agent Mycobacterium tuberculosis (Mtb). 
      Mtb has various survival strategies, including blockade of phagosome maturation 
      and inhibition of antigen presentation. Lysophosphatidylcholine (LPC) is a major 
      phospholipid component of oxidized low-density lipoprotein and is involved in 
      various cellular responses, such as activation of second messengers and 
      bactericidal activity in neutrophils. In this study, macrophages were infected 
      with a low infectious dose of Mtb and treated with LPC to investigate the 
      bactericidal activity of LPC against Mtb. In macrophages infected with Mtb 
      strain, H37Ra or H37Rv, LPC suppressed bacterial growth; however, this effect was 
      suppressed in bone marrow-derived macrophages (BMDMs) isolated from G2A (a G 
      protein-coupled receptor involved in some LPC actions) knockout mice. LPC also 
      promoted phagosome maturation via phosphatidylinositol 3 kinase (PI3K)-p38 
      mitogen-activated protein kinase (MAPK)-mediated reactive oxygen species 
      production and intracellular Ca(2+) release during Mtb infection. In addition, 
      LPC induced increased levels of intracellular cyclic adenosine monophosphate 
      (cAMP) and phosphorylated glycogen synthase kinase 3 beta (GSK3beta) in Mtb-infected 
      macrophages. Protein kinase A (PKA)-induced phosphorylation of GSK3beta suppressed 
      activation of NF-kappaB in LPC-treated macrophages during Mtb infection, leading to 
      decreased secretion of pro-inflammatory cytokines and increased secretion of 
      anti-inflammatory cytokines. These results suggest that LPC can effectively 
      control Mtb growth by promoting phagosome maturation via cAMP-induced activation 
      of the PKA-PI3K-p38 MAPK pathway. Moreover, LPC can regulate excessive production 
      of pro-inflammatory cytokines associated with bacterial infection of macrophages.
FAU - Lee, Hyo-Ji
AU  - Lee HJ
AD  - Department of Biological Sciences, Kangwon National University, Chuncheon, South 
      Korea.
AD  - Institute of Life Sciences, Kangwon National University, Chuncheon, South Korea.
FAU - Ko, Hyun-Jeong
AU  - Ko HJ
AD  - College of Pharmacy, Kangwon National University, Chuncheon, South Korea.
FAU - Song, Dong-Kun
AU  - Song DK
AD  - Department of Pharmacology, College of Medicine, Hallym University, Chuncheon, 
      South Korea.
FAU - Jung, Yu-Jin
AU  - Jung YJ
AD  - Department of Biological Sciences, Kangwon National University, Chuncheon, South 
      Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180427
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Cytokines)
RN  - 0 (Lysophosphatidylcholines)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/immunology/*metabolism
MH  - Cytokines/immunology
MH  - Cytoplasm/metabolism
MH  - Lysophosphatidylcholines/*pharmacology
MH  - Macrophages/drug effects/*microbiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mycobacterium tuberculosis
MH  - Phagosomes/drug effects/*physiology
MH  - Phosphatidylinositol 3-Kinase/*metabolism
MH  - Phosphorylation
MH  - RAW 264.7 Cells
MH  - Reactive Oxygen Species/metabolism
MH  - *Signal Transduction
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
PMC - PMC5934435
OTO - NOTNLM
OT  - Mycobacterium tuberculosis
OT  - inflammation
OT  - lysophosphatidylcholine
OT  - macrophage
OT  - phagosome maturation
EDAT- 2018/05/15 06:00
MHDA- 2018/05/15 06:01
PMCR- 2018/01/01
CRDT- 2018/05/15 06:00
PHST- 2018/01/09 00:00 [received]
PHST- 2018/04/13 00:00 [accepted]
PHST- 2018/05/15 06:00 [entrez]
PHST- 2018/05/15 06:00 [pubmed]
PHST- 2018/05/15 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2018.00920 [doi]
PST - epublish
SO  - Front Immunol. 2018 Apr 27;9:920. doi: 10.3389/fimmu.2018.00920. eCollection 
      2018.