PMID- 37094780
OWN - NLM
STAT- MEDLINE
DCOM- 20230612
LR  - 20231116
IS  - 1098-8823 (Print)
IS  - 1098-8823 (Linking)
VI  - 167
DP  - 2023 Aug
TI  - Microsomal prostaglandin E synthase-1 inhibition promotes shunting in arachidonic 
      acid metabolism during inflammatory responses in vitro.
PG  - 106738
LID - S1098-8823(23)00035-7 [pii]
LID - 10.1016/j.prostaglandins.2023.106738 [doi]
AB  - Microsomal Prostaglandin E Synthase 1 (mPGES-1) is the key enzyme for the 
      generation of the pro-inflammatory lipid mediator prostaglandin E(2) (PGE(2)), 
      which contributes to several pathological features of many diseases. Inhibition 
      of mPGES-1 has been shown to be a safe and effective therapeutic strategy in 
      various pre-clinical studies. In addition to reduced PGE(2) formation, it is also 
      suggested that the potential shunting into other protective and pro-resolving 
      prostanoids may play an important role in resolution of inflammation. In the 
      present study, we analysed the eicosanoid profiles in four in vitro inflammation 
      models and compared the effects of mPGES-1 inhibition with those of 
      cyclooxygenase-2 (Cox-2) inhibition. Our results showed a marked shift to the 
      PGD(2) pathway under mPGES-1 inhibition in A549 cells, RAW264.7 cells and mouse 
      bone marrow-derived macrophages (BMDMs), whereas enhanced prostacyclin production 
      was observed in rheumatoid arthritis synovial fibroblasts (RASFs) treated with an 
      mPGES-1 inhibitor. As expected, Cox-2 inhibition completely suppressed all 
      prostanoids. This study suggests that the therapeutic effects of mPGES-1 
      inhibition may be mediated by modulation of other prostanoids in addition to 
      PGE(2) reduction.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Liu, Jianyang
AU  - Liu J
AD  - Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet 
      and Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
FAU - Peng, Bing
AU  - Peng B
AD  - Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet 
      and Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
FAU - Steinmetz-Spah, Julia
AU  - Steinmetz-Spah J
AD  - Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet 
      and Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
FAU - Idborg, Helena
AU  - Idborg H
AD  - Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet 
      and Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
FAU - Korotkova, Marina
AU  - Korotkova M
AD  - Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet 
      and Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
FAU - Jakobsson, Per-Johan
AU  - Jakobsson PJ
AD  - Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet 
      and Karolinska University Hospital, SE-171 76 Stockholm, Sweden. Electronic 
      address: per-johan.jakobsson@ki.se.
LA  - eng
PT  - Journal Article
DEP - 20230423
PL  - United States
TA  - Prostaglandins Other Lipid Mediat
JT  - Prostaglandins & other lipid mediators
JID - 9808648
RN  - EC 5.3.99.3 (Prostaglandin-E Synthases)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 0 (Prostaglandins)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - 0 (Eicosanoids)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Prostaglandin-E Synthases/metabolism
MH  - Cyclooxygenase 2/metabolism
MH  - Arachidonic Acid
MH  - *Prostaglandins
MH  - *Inflammation/drug therapy/metabolism
MH  - Dinoprostone/metabolism
MH  - Eicosanoids
OTO - NOTNLM
OT  - A549
OT  - BMDM
OT  - LC-MS/MS
OT  - RASF
OT  - RAW 264.7
OT  - inflammation
OT  - mPGES-1
OT  - prostanoids
COIS- Declaration of Competing Interest The authors declare that they have no conflict 
      of interest.
EDAT- 2023/04/25 00:41
MHDA- 2023/06/12 06:42
CRDT- 2023/04/24 07:25
PHST- 2023/02/17 00:00 [received]
PHST- 2023/04/14 00:00 [revised]
PHST- 2023/04/21 00:00 [accepted]
PHST- 2023/06/12 06:42 [medline]
PHST- 2023/04/25 00:41 [pubmed]
PHST- 2023/04/24 07:25 [entrez]
AID - S1098-8823(23)00035-7 [pii]
AID - 10.1016/j.prostaglandins.2023.106738 [doi]
PST - ppublish
SO  - Prostaglandins Other Lipid Mediat. 2023 Aug;167:106738. doi: 
      10.1016/j.prostaglandins.2023.106738. Epub 2023 Apr 23.