PMID- 34829577
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211130
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 10
IP  - 11
DP  - 2021 Oct 27
TI  - S1P/S1P(2) Signaling Axis Regulates Both NLRP3 Upregulation and NLRP3 
      Inflammasome Activation in Macrophages Primed with Lipopolysaccharide.
LID - 10.3390/antiox10111706 [doi]
LID - 1706
AB  - The activation of NLRP3 inflammasome is a key factor for various inflammatory 
      diseases. Here, we provide experimental evidence supporting the regulatory role 
      of sphingosine-1-phosphate (S1P) in NLRP3 inflammasome activation in mouse 
      bone-marrow-derived macrophages (BMDMs), along with the S1P receptor subtype 
      involved and underlying regulatory mechanisms. During the priming stage, S1P 
      induced NLRP3 upregulation in BMDMs only when primed with lipopolysaccharide 
      (LPS). In this event, S1P(2), but not S1P(1), was involved based on the 
      attenuated NLRP3 upregulation with JTE013 (S1P(2) antagonist) or S1P(2) 
      knockdown. During the activation stage, S1P induced NLRP3 inflammasome activation 
      in LPS-primed BMDMs via caspase-1 activation, interleukin 1beta maturation, 
      apoptosis-associated speck-like protein containing a CARD (ASC) speck formation, 
      and IL-1beta secretion. Such NLRP3 inflammasome activation was blocked by either 
      pharmacological inhibition or genetic knockdown of S1P(2). NF-kappaB, PI3K/Akt, and 
      ERK1/2 were identified as effector pathways underlying S1P/S1P(2) signaling in 
      the regulation of NLRP3 upregulation in LPS-primed BMDMs. Further, reactive 
      oxygen species (ROS) production was dependent on the S1P/S1P(2) signaling axis in 
      these cells, and the ROS generated regulate NLRP3 inflammasome activation, but 
      not NLRP3 priming. Collectively, our findings suggest that S1P promotes NLRP3 
      upregulation and NLRP3 inflammasome activation in LPS-primed BMDMs via S1P(2) and 
      subsequent effector pathways.
FAU - Lee, Chi-Ho
AU  - Lee CH
AUID- ORCID: 0000-0002-3466-2104
AD  - Laboratory of Neuropharmacology, College of Pharmacy and Gachon Institute of 
      Pharmaceutical Sciences, Incheon 21936, Korea.
FAU - Choi, Ji Woong
AU  - Choi JW
AD  - Laboratory of Neuropharmacology, College of Pharmacy and Gachon Institute of 
      Pharmaceutical Sciences, Incheon 21936, Korea.
LA  - eng
GR  - NRF-2021R1A2C1005520/National Research Foundation of Korea/
GR  - NRF-2020R1A6A1A03043708/National Research Foundation of Korea/
PT  - Journal Article
DEP - 20211027
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC8614891
OTO - NOTNLM
OT  - LPS
OT  - NLRP3 inflammasome activation
OT  - NLRP3 upregulation
OT  - S1P
OT  - S1P2
OT  - bone marrow-derived macrophage
COIS- The authors declare no conflict of interest.
EDAT- 2021/11/28 06:00
MHDA- 2021/11/28 06:01
PMCR- 2021/10/27
CRDT- 2021/11/27 01:09
PHST- 2021/10/01 00:00 [received]
PHST- 2021/10/21 00:00 [revised]
PHST- 2021/10/25 00:00 [accepted]
PHST- 2021/11/27 01:09 [entrez]
PHST- 2021/11/28 06:00 [pubmed]
PHST- 2021/11/28 06:01 [medline]
PHST- 2021/10/27 00:00 [pmc-release]
AID - antiox10111706 [pii]
AID - antioxidants-10-01706 [pii]
AID - 10.3390/antiox10111706 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2021 Oct 27;10(11):1706. doi: 10.3390/antiox10111706.