Phosphatidylserine enhances anti-inflammatory effects of reconstituted HDL in macrophages via distinct intracellular pathways

Phosphatidylserine (PS) is a minor phospholipid constituent of high-density lipoprotein (HDL) that exhibits potent anti-inflammatory activity. It remains indeterminate whether PS incorporation can enhance anti-inflammatory effects of reconstituted HDL (rHDL). Human macrophages were treated with rHDL...

Full description

Saved in:
Bibliographic Details
Published in:The FASEB journal Vol. 36; no. 5; p. e22274
Main Authors: Darabi, Maryam, Lhomme, Marie, Dahik, Veronica D, Guillas, Isabelle, Frisdal, Eric, Tubeuf, Emilie, Poupel, Lucie, Patel, Mili, Gautier, Emmanuel L, Huby, Thierry, Guerin, Maryse, Rye, Kerry-Anne, Lesnik, Philippe, Le Goff, Wilfried, Kontush, Anatol
Format: Journal Article
Language:English
Published: United States 01.05.2022
Subjects:
Animals
Anti-Inflammatory Agents - metabolism
Anti-Inflammatory Agents - pharmacology
Lipoproteins, HDL - metabolism
Macrophages - metabolism
Mice
p38 Mitogen-Activated Protein Kinases - metabolism
Phosphatidylserines - metabolism
atherosclerosis
rHDL
phospholipids
inflammation
ISSN:1530-6860, 1530-6860
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Abstract Phosphatidylserine (PS) is a minor phospholipid constituent of high-density lipoprotein (HDL) that exhibits potent anti-inflammatory activity. It remains indeterminate whether PS incorporation can enhance anti-inflammatory effects of reconstituted HDL (rHDL). Human macrophages were treated with rHDL containing phosphatidylcholine alone (PC-rHDL) or PC and PS (PC/PS-rHDL). Interleukin (IL)-6 secretion and expression was more strongly inhibited by PC/PS-rHDL than PC-rHDL in both tumor necrosis factor (TNF)-α- and lipopolysaccharide (LPS)-stimulated macrophages. siRNA experiments revealed that the enhanced anti-inflammatory effects of PC/PS-rHDL required scavenger receptor class B type I (SR-BI). Furthermore, PC/PS-rHDL induced a greater increase in Akt1/2/3 phosphorylation than PC-rHDL. In addition, PC/PS but not PC-rHDL decreased the abundance of plasma membrane lipid rafts and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation. Finally, when these rHDL formulations were administered to dyslipidemic low-density lipoprotein (LDL)-receptor knockout mice fed a high-cholesterol diet, circulating IL-6 levels were significantly reduced only in PC/PS-rHDL-treated mice. In parallel, enhanced Akt1/2/3 phosphorylation by PC/PS-rHDL was observed in the mouse aortic tissue using immunohistochemistry. We concluded that the incorporation of PS into rHDLs enhanced their anti-inflammatory activity by modulating Akt1/2/3- and p38 MAPK-mediated signaling through SR-BI in stimulated macrophages. These data identify PS as a potent anti-inflammatory component capable of enhancing therapeutic potential of rHDL-based therapy.
AbstractList Phosphatidylserine (PS) is a minor phospholipid constituent of high-density lipoprotein (HDL) that exhibits potent anti-inflammatory activity. It remains indeterminate whether PS incorporation can enhance anti-inflammatory effects of reconstituted HDL (rHDL). Human macrophages were treated with rHDL containing phosphatidylcholine alone (PC-rHDL) or PC and PS (PC/PS-rHDL). Interleukin (IL)-6 secretion and expression was more strongly inhibited by PC/PS-rHDL than PC-rHDL in both tumor necrosis factor (TNF)-α- and lipopolysaccharide (LPS)-stimulated macrophages. siRNA experiments revealed that the enhanced anti-inflammatory effects of PC/PS-rHDL required scavenger receptor class B type I (SR-BI). Furthermore, PC/PS-rHDL induced a greater increase in Akt1/2/3 phosphorylation than PC-rHDL. In addition, PC/PS but not PC-rHDL decreased the abundance of plasma membrane lipid rafts and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation. Finally, when these rHDL formulations were administered to dyslipidemic low-density lipoprotein (LDL)-receptor knockout mice fed a high-cholesterol diet, circulating IL-6 levels were significantly reduced only in PC/PS-rHDL-treated mice. In parallel, enhanced Akt1/2/3 phosphorylation by PC/PS-rHDL was observed in the mouse aortic tissue using immunohistochemistry. We concluded that the incorporation of PS into rHDLs enhanced their anti-inflammatory activity by modulating Akt1/2/3- and p38 MAPK-mediated signaling through SR-BI in stimulated macrophages. These data identify PS as a potent anti-inflammatory component capable of enhancing therapeutic potential of rHDL-based therapy.
Phosphatidylserine (PS) is a minor phospholipid constituent of high-density lipoprotein (HDL) that exhibits potent anti-inflammatory activity. It remains indeterminate whether PS incorporation can enhance anti-inflammatory effects of reconstituted HDL (rHDL). Human macrophages were treated with rHDL containing phosphatidylcholine alone (PC-rHDL) or PC and PS (PC/PS-rHDL). Interleukin (IL)-6 secretion and expression was more strongly inhibited by PC/PS-rHDL than PC-rHDL in both tumor necrosis factor (TNF)-α- and lipopolysaccharide (LPS)-stimulated macrophages. siRNA experiments revealed that the enhanced anti-inflammatory effects of PC/PS-rHDL required scavenger receptor class B type I (SR-BI). Furthermore, PC/PS-rHDL induced a greater increase in Akt1/2/3 phosphorylation than PC-rHDL. In addition, PC/PS but not PC-rHDL decreased the abundance of plasma membrane lipid rafts and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation. Finally, when these rHDL formulations were administered to dyslipidemic low-density lipoprotein (LDL)-receptor knockout mice fed a high-cholesterol diet, circulating IL-6 levels were significantly reduced only in PC/PS-rHDL-treated mice. In parallel, enhanced Akt1/2/3 phosphorylation by PC/PS-rHDL was observed in the mouse aortic tissue using immunohistochemistry. We concluded that the incorporation of PS into rHDLs enhanced their anti-inflammatory activity by modulating Akt1/2/3- and p38 MAPK-mediated signaling through SR-BI in stimulated macrophages. These data identify PS as a potent anti-inflammatory component capable of enhancing therapeutic potential of rHDL-based therapy.Phosphatidylserine (PS) is a minor phospholipid constituent of high-density lipoprotein (HDL) that exhibits potent anti-inflammatory activity. It remains indeterminate whether PS incorporation can enhance anti-inflammatory effects of reconstituted HDL (rHDL). Human macrophages were treated with rHDL containing phosphatidylcholine alone (PC-rHDL) or PC and PS (PC/PS-rHDL). Interleukin (IL)-6 secretion and expression was more strongly inhibited by PC/PS-rHDL than PC-rHDL in both tumor necrosis factor (TNF)-α- and lipopolysaccharide (LPS)-stimulated macrophages. siRNA experiments revealed that the enhanced anti-inflammatory effects of PC/PS-rHDL required scavenger receptor class B type I (SR-BI). Furthermore, PC/PS-rHDL induced a greater increase in Akt1/2/3 phosphorylation than PC-rHDL. In addition, PC/PS but not PC-rHDL decreased the abundance of plasma membrane lipid rafts and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation. Finally, when these rHDL formulations were administered to dyslipidemic low-density lipoprotein (LDL)-receptor knockout mice fed a high-cholesterol diet, circulating IL-6 levels were significantly reduced only in PC/PS-rHDL-treated mice. In parallel, enhanced Akt1/2/3 phosphorylation by PC/PS-rHDL was observed in the mouse aortic tissue using immunohistochemistry. We concluded that the incorporation of PS into rHDLs enhanced their anti-inflammatory activity by modulating Akt1/2/3- and p38 MAPK-mediated signaling through SR-BI in stimulated macrophages. These data identify PS as a potent anti-inflammatory component capable of enhancing therapeutic potential of rHDL-based therapy.
Author Darabi, Maryam
Huby, Thierry
Kontush, Anatol
Le Goff, Wilfried
Lhomme, Marie
Lesnik, Philippe
Guerin, Maryse
Poupel, Lucie
Tubeuf, Emilie
Rye, Kerry-Anne
Patel, Mili
Frisdal, Eric
Dahik, Veronica D
Gautier, Emmanuel L
Guillas, Isabelle
Author_xml – sequence: 1
  givenname: Maryam
  surname: Darabi
  fullname: Darabi, Maryam
  organization: INSERM, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, Sorbonne Université, Paris, France
– sequence: 2
  givenname: Marie
  surname: Lhomme
  fullname: Lhomme, Marie
  organization: ICAN Analytics, Lipidomics Core, Foundation for Innovation in Cardiometabolism and Nutrition (IHU-ICAN, ANR-10-IAHU-05), Paris, France
– sequence: 3
  givenname: Veronica D
  surname: Dahik
  fullname: Dahik, Veronica D
  organization: INSERM, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, Sorbonne Université, Paris, France
– sequence: 4
  givenname: Isabelle
  surname: Guillas
  fullname: Guillas, Isabelle
  organization: INSERM, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, Sorbonne Université, Paris, France
– sequence: 5
  givenname: Eric
  surname: Frisdal
  fullname: Frisdal, Eric
  organization: INSERM, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, Sorbonne Université, Paris, France
– sequence: 6
  givenname: Emilie
  surname: Tubeuf
  fullname: Tubeuf, Emilie
  organization: INSERM, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, Sorbonne Université, Paris, France
– sequence: 7
  givenname: Lucie
  surname: Poupel
  fullname: Poupel, Lucie
  organization: INSERM, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, Sorbonne Université, Paris, France
– sequence: 8
  givenname: Mili
  surname: Patel
  fullname: Patel, Mili
  organization: School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
– sequence: 9
  givenname: Emmanuel L
  surname: Gautier
  fullname: Gautier, Emmanuel L
  organization: INSERM, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, Sorbonne Université, Paris, France
– sequence: 10
  givenname: Thierry
  surname: Huby
  fullname: Huby, Thierry
  organization: INSERM, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, Sorbonne Université, Paris, France
– sequence: 11
  givenname: Maryse
  surname: Guerin
  fullname: Guerin, Maryse
  organization: INSERM, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, Sorbonne Université, Paris, France
– sequence: 12
  givenname: Kerry-Anne
  surname: Rye
  fullname: Rye, Kerry-Anne
  organization: School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
– sequence: 13
  givenname: Philippe
  surname: Lesnik
  fullname: Lesnik, Philippe
  organization: INSERM, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, Sorbonne Université, Paris, France
– sequence: 14
  givenname: Wilfried
  surname: Le Goff
  fullname: Le Goff, Wilfried
  organization: INSERM, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, Sorbonne Université, Paris, France
– sequence: 15
  givenname: Anatol
  surname: Kontush
  fullname: Kontush, Anatol
  organization: INSERM, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, Sorbonne Université, Paris, France
BackLink https://www.ncbi.nlm.nih.gov/pubmed/35416331$$D View this record in MEDLINE/PubMed
BookMark eNpNkMtLxDAQxoOsuA89epUcvXRN-kjSo6yPFRYU0XOZTRObpU3XJFV68H834gqeZmB-8833zRxNbG8VQueULCkp2ZXeLVNCBSGCkucjNKNFRhImGJn866do7v2OEEIJZSdomhU5ZVlGZ-jrqen9voFg6rH1yhmrsLINWKk8BhtMYqxuoesg9G7ESmslg8e9xk7J3vpgwhBUjdc3G2ws7kC6Psq9xe0PA7g2kbAyxFlwIFXbDi04vIfQfMLoT9Gxhnj27FAX6PXu9mW1TjaP9w-r600ic87zRNQSKKdMc-BlTJByQdOMKqq3QtJCCS2gyPIy55DWRR6D5YJJEEpTvgXB0gW6_NXdu_59UD5UnfE_bsCqfvBVyvKyLAUvRUQvDuiw7VRd7Z3pwI3V38vSbytRcZ4
CitedBy_id crossref_primary_10_1186_s13104_024_06885_7
crossref_primary_10_1016_j_biopha_2024_117200
crossref_primary_10_3390_pharmaceutics15051504
crossref_primary_10_3390_membranes13010083
crossref_primary_10_3390_ijms242216036
crossref_primary_10_1186_s12872_025_04752_2
crossref_primary_10_3390_antiox13010057
crossref_primary_10_1152_ajpcell_00395_2025
crossref_primary_10_1111_1750_3841_70335
crossref_primary_10_1161_CIRCRESAHA_123_321563
crossref_primary_10_1016_j_jacl_2023_07_003
crossref_primary_10_1016_j_jlr_2024_100678
crossref_primary_10_1016_j_jlr_2025_100799
ContentType Journal Article
Copyright 2022 Federation of American Societies for Experimental Biology.
Copyright_xml – notice: 2022 Federation of American Societies for Experimental Biology.
DBID CGR
CUY
CVF
ECM
EIF
NPM
7X8
DOI 10.1096/fj.201800810R
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
MEDLINE - Academic
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
MEDLINE - Academic
DatabaseTitleList MEDLINE
MEDLINE - Academic
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: 7X8
  name: MEDLINE - Academic
  url: https://search.proquest.com/medline
  sourceTypes: Aggregation Database
DeliveryMethod no_fulltext_linktorsrc
Discipline Biology
EISSN 1530-6860
ExternalDocumentID 35416331
Genre Research Support, Non-U.S. Gov't
Journal Article
GroupedDBID ---
-DZ
-~X
.55
0R~
0VX
123
18M
1OB
1OC
29H
2WC
33P
34G
39C
3O-
4.4
53G
5GY
5RE
85S
AAHQN
AAMMB
AAMNL
AANLZ
AAYCA
ABCUV
ABDNZ
ABEFU
ABJNI
ABOCM
ACCZN
ACGFS
ACIWK
ACNCT
ACPOU
ACPRK
ACXQS
ACYGS
ADKYN
ADXHL
ADZMN
AEFGJ
AEIGN
AENEX
AEUYR
AEYWJ
AFFNX
AFFPM
AFRAH
AFWVQ
AGCDD
AGHNM
AGXDD
AGYGG
AHBTC
AI.
AIDQK
AIDYY
AITYG
AIURR
AIZAD
ALMA_UNASSIGNED_HOLDINGS
ALUQN
ALVPJ
AMYDB
BFHJK
BIYOS
C1A
CGR
CS3
CUY
CVF
DCZOG
DU5
D~5
E3Z
EBS
ECM
EIF
EJD
F5P
F9R
H13
HGLYW
HZ~
H~9
J5H
L7B
LATKE
LEEKS
MEWTI
MVM
NEJ
NPM
O9-
OHT
OVD
Q-A
RHI
RJQFR
ROL
SAMSI
SJN
SUPJJ
TEORI
TFA
TR2
TWZ
U18
VH1
W8F
WH7
WHG
WOQ
WXSBR
X7M
XJT
XOL
XSW
Y6R
YBU
YHG
YKV
YNH
YSK
Z0Y
ZCA
ZE2
ZGI
ZXP
~KM
7X8
ID FETCH-LOGICAL-c4774-8dca1716f7a790162781231e1fb8c15e8f8a534947a2d54331486ca8ef17ba862
IEDL.DBID 7X8
ISICitedReferencesCount 16
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000781730700001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN 1530-6860
IngestDate Wed Oct 01 13:41:21 EDT 2025
Mon Jul 21 06:00:19 EDT 2025
IsDoiOpenAccess false
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 5
Keywords atherosclerosis
rHDL
phospholipids
inflammation
Language English
License 2022 Federation of American Societies for Experimental Biology.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c4774-8dca1716f7a790162781231e1fb8c15e8f8a534947a2d54331486ca8ef17ba862
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
OpenAccessLink https://onlinelibrary.wiley.com/doi/pdfdirect/10.1096/fj.201800810R
PMID 35416331
PQID 2649998798
PQPubID 23479
ParticipantIDs proquest_miscellaneous_2649998798
pubmed_primary_35416331
PublicationCentury 2000
PublicationDate May 2022
PublicationDateYYYYMMDD 2022-05-01
PublicationDate_xml – month: 05
  year: 2022
  text: May 2022
PublicationDecade 2020
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle The FASEB journal
PublicationTitleAlternate FASEB J
PublicationYear 2022
SSID ssj0001016
Score 2.4718697
Snippet Phosphatidylserine (PS) is a minor phospholipid constituent of high-density lipoprotein (HDL) that exhibits potent anti-inflammatory activity. It remains...
SourceID proquest
pubmed
SourceType Aggregation Database
Index Database
StartPage e22274
SubjectTerms Animals
Anti-Inflammatory Agents - metabolism
Anti-Inflammatory Agents - pharmacology
Lipoproteins, HDL - metabolism
Macrophages - metabolism
Mice
p38 Mitogen-Activated Protein Kinases - metabolism
Phosphatidylserines - metabolism
Title Phosphatidylserine enhances anti-inflammatory effects of reconstituted HDL in macrophages via distinct intracellular pathways
URI https://www.ncbi.nlm.nih.gov/pubmed/35416331
https://www.proquest.com/docview/2649998798
Volume 36
WOSCitedRecordID wos000781730700001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText
inHoldings 1
isFullTextHit
isPrint
link http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS8NAEF7UKnjx_agvVvAaTDaP3ZxE1NKDliIKvYXNPkjFJrWplR78784kKT0JgpdcQsiyMzv7ze7M9xFyFbqSW6aQDM-XTmCFcmIjU4dpK6T2lBCmFpvgvZ4YDOJ-c-BWNmWVi5hYBWpdKDwjv4aNG7CM4LG4GX84qBqFt6uNhMYqacG_YvRqPliyhWNmWvOlQookIrfh2ATUfm3fsKxL4I7oPv-OLqtdprP93_HtkK0GX9Lb2iF2yYrJ98hGrTg53yff_awoxxmYQ8_fy6r1j5o8Q9OXFCZ56IDHgZOMqst32lR70MLSKnNuCgs07d4_0mFORxIVwDKISSWdDSXVGDFyNYV304nESwGscqUoe_wl5-UBee08vNx1nUaBwVEB4EJHaCWRT8dyyQE4RIwDHvA949lUKC80AgwaIsENl0yH2HwViEhJYazHUwnJ0iFZy4vcHBPqs5DF2g24YhZSnjSWyouDwPAotIGQcZtcLuY1AQ_HEcrcFJ9lspzZNjmqjZOMayqOxA8RUPreyR--PiWbDHsXqmrFM9KysL7NOVlXs-mwnFxUrgPPXv_pBwZu0Nc
linkProvider ProQuest
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Phosphatidylserine+enhances+anti-inflammatory+effects+of+reconstituted+HDL+in+macrophages+via+distinct+intracellular+pathways&rft.jtitle=The+FASEB+journal&rft.au=Darabi%2C+Maryam&rft.au=Lhomme%2C+Marie&rft.au=Dahik%2C+Veronica+D&rft.au=Guillas%2C+Isabelle&rft.date=2022-05-01&rft.issn=1530-6860&rft.eissn=1530-6860&rft.volume=36&rft.issue=5&rft.spage=e22274&rft_id=info:doi/10.1096%2Ffj.201800810R&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1530-6860&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1530-6860&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1530-6860&client=summon