PMID- 32395118
OWN - NLM
STAT- MEDLINE
DCOM- 20210331
LR  - 20210331
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - 1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol (PLAG) Mitigates Monosodium Urate 
      (MSU)-Induced Acute Gouty Inflammation in BALB/c Mice.
PG  - 710
LID - 10.3389/fimmu.2020.00710 [doi]
LID - 710
AB  - Acute gouty arthritis is an auto-inflammatory disease caused by the deposition of 
      monosodium urate (MSU) crystals in joints or tissues. Excessive neutrophil 
      recruitment into gouty lesions is a general clinical sign and induces a pain 
      phenotype. Attenuation of successive periods of neutrophil infiltration might be 
      a beneficial approach to achieve therapeutic efficacy. In this study, the 
      activity of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) in attenuation 
      of excess neutrophil infiltration was assessed in gout-induced lesions of BALB/c 
      mice. Neutrophil infiltration in MSU-induced gouty lesions was analyzed using 
      immunohistochemical staining. ELISA and RT-PCR were used to measure attenuation 
      of expression of the major neutrophil chemoattractant, CXC motif chemokine ligand 
      8 (CXCL8), in a PLAG-treated animal model and in cells in vitro. The animal model 
      revealed massive increased neutrophil infiltration in the MSU-induced gouty 
      lesions, but the PLAG-treated mice had significantly reduced neutrophil numbers 
      in these lesions. The results also indicated that the MSU crystals stimulated a 
      damage-associated molecular pattern that was recognized by the P2Y6 purinergic 
      receptor. This MSU-stimulated P2Y6 receptor was destined to intracellular 
      trafficking. During intracellular endosomal trafficking of the receptor, 
      endosome-dependent signaling provided expression of CXCL8 chemokines for 
      neutrophil recruitment. PLAG accelerated initiation of the intracellular 
      trafficking of the P2Y6 receptor and returning the receptor to the membrane. This 
      process shortened the intracellular retention time of the receptor anchoring 
      endosome and subsequently attenuated endosome-dependent signaling for CXCL8 
      expression. These study results suggested that PLAG could be used for resolution 
      of acute inflammation induced in gout lesions.
CI  - Copyright (c) 2020 Shin, Jeong, Kim, Sohn, Yoon and Kim.
FAU - Shin, Su-Hyun
AU  - Shin SH
AD  - Division of Systems Biology and Bioengineering, Cell Factory Research Center, 
      Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
AD  - Department of Functional Genomics, University of Science and Technology, Daejeon, 
      South Korea.
FAU - Jeong, Jinseon
AU  - Jeong J
AD  - Division of Global New Drug Development, ENZYCHEM Lifesciences, Seoul, South 
      Korea.
FAU - Kim, Joo Heon
AU  - Kim JH
AD  - Department of Pathology, EulJi University School of Medicine, Daejeon, South 
      Korea.
FAU - Sohn, Ki-Young
AU  - Sohn KY
AD  - Division of Global New Drug Development, ENZYCHEM Lifesciences, Seoul, South 
      Korea.
FAU - Yoon, Sun Young
AU  - Yoon SY
AD  - Division of Global New Drug Development, ENZYCHEM Lifesciences, Seoul, South 
      Korea.
FAU - Kim, Jae Wha
AU  - Kim JW
AD  - Division of Systems Biology and Bioengineering, Cell Factory Research Center, 
      Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
AD  - Department of Functional Genomics, University of Science and Technology, Daejeon, 
      South Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200424
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (1-palmitoyl-2-linoleoyl-3-acetyl-rac glycerol)
RN  - 0 (CXCL8 protein, human)
RN  - 0 (Diglycerides)
RN  - 0 (Interleukin-8)
RN  - 0 (Receptors, Purinergic P2)
RN  - 0 (purinoceptor P2Y6)
RN  - 268B43MJ25 (Uric Acid)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Arthritis, Gouty/*chemically induced/*drug therapy/immunology
MH  - Cell Movement/immunology
MH  - Diglycerides/*therapeutic use
MH  - Disease Models, Animal
MH  - Humans
MH  - Inflammation/chemically induced/drug therapy
MH  - Interleukin-8/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neutrophil Infiltration/drug effects
MH  - Neutrophils/immunology
MH  - Receptors, Purinergic P2/metabolism
MH  - Signal Transduction/drug effects
MH  - THP-1 Cells
MH  - Uric Acid/*adverse effects
PMC - PMC7196669
OTO - NOTNLM
OT  - GPCR
OT  - chemokine
OT  - gouty inflammation
OT  - neutrophil
OT  - receptor trafficking
EDAT- 2020/05/13 06:00
MHDA- 2021/04/01 06:00
PMCR- 2020/01/01
CRDT- 2020/05/13 06:00
PHST- 2019/10/24 00:00 [received]
PHST- 2020/03/30 00:00 [accepted]
PHST- 2020/05/13 06:00 [entrez]
PHST- 2020/05/13 06:00 [pubmed]
PHST- 2021/04/01 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.00710 [doi]
PST - epublish
SO  - Front Immunol. 2020 Apr 24;11:710. doi: 10.3389/fimmu.2020.00710. eCollection 
      2020.