Arachidonic Acid Cascade and Eicosanoid Production Are Elevated While LTC4 Synthase Modulates the Lipidomics Profile in the Brain of the HIVgp120-Transgenic Mouse Model of NeuroHIV.
HANDs
HIV
LTC4S
arachidonic acid
cell signaling
eicosanoids
lipidomics
mRNA
neuroinflammation
sexual dimorphism
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
05 07 2022
05 07 2022
Historique:
received:
21
05
2022
revised:
24
06
2022
accepted:
26
06
2022
entrez:
9
7
2022
pubmed:
10
7
2022
medline:
14
7
2022
Statut:
epublish
Résumé
Combination antiretroviral therapy (cART) has transformed HIV infection from a terminal disease to a manageable chronic health condition, extending patients' life expectancy to that of the general population. However, the incidence of HIV-associated neurocognitive disorders (HANDs) has persisted despite virological suppression. Patients with HIV display persistent signs of immune activation and inflammation despite cART. The arachidonic acid (AA) cascade is an important immune response system responsible for both pro- and anti-inflammatory processes. Lipidomics, mRNA and Western blotting analysis provide valuable insights into the molecular mechanisms surrounding arachidonic acid metabolism and the resulting inflammation caused by perturbations thereof. Here, we report the presence of inflammatory eicosanoids in the brains of a transgenic mouse model of NeuroHIV that expresses soluble HIV-1 envelope glycoprotein in glial cells (HIVgp120tg mice). Additionally, we report that the effect of LTC4S knockout in HIVgp120tg mice resulted in the sexually dimorphic transcription of COX- and 5-LOX-related genes. Furthermore, the absence of LTC4S suppressed ERK1/2 and p38 MAPK signaling activity in female mice only. The mass spectrometry-based lipidomic profiling of these mice reveals beneficial alterations to lipids in the brain. Targeting the AA cascade may hold potential in the treatment of neuroinflammation observed in NeuroHIV and HANDs.
Sections du résumé
BACKGROUND
Combination antiretroviral therapy (cART) has transformed HIV infection from a terminal disease to a manageable chronic health condition, extending patients' life expectancy to that of the general population. However, the incidence of HIV-associated neurocognitive disorders (HANDs) has persisted despite virological suppression. Patients with HIV display persistent signs of immune activation and inflammation despite cART. The arachidonic acid (AA) cascade is an important immune response system responsible for both pro- and anti-inflammatory processes.
METHODS
Lipidomics, mRNA and Western blotting analysis provide valuable insights into the molecular mechanisms surrounding arachidonic acid metabolism and the resulting inflammation caused by perturbations thereof.
RESULTS
Here, we report the presence of inflammatory eicosanoids in the brains of a transgenic mouse model of NeuroHIV that expresses soluble HIV-1 envelope glycoprotein in glial cells (HIVgp120tg mice). Additionally, we report that the effect of LTC4S knockout in HIVgp120tg mice resulted in the sexually dimorphic transcription of COX- and 5-LOX-related genes. Furthermore, the absence of LTC4S suppressed ERK1/2 and p38 MAPK signaling activity in female mice only. The mass spectrometry-based lipidomic profiling of these mice reveals beneficial alterations to lipids in the brain.
CONCLUSION
Targeting the AA cascade may hold potential in the treatment of neuroinflammation observed in NeuroHIV and HANDs.
Identifiants
pubmed: 35805207
pii: cells11132123
doi: 10.3390/cells11132123
pmc: PMC9265961
pii:
doi:
Substances chimiques
Eicosanoids
0
HIV Envelope Protein gp120
0
Arachidonic Acid
27YG812J1I
Glutathione Transferase
EC 2.5.1.18
leukotriene-C4 synthase
EC 4.4.1.20
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIMH NIH HHS
ID : R01 MH105330
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH104131
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG044271
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA052209
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH087332
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG013319
Pays : United States
Références
J Neuroimmunol. 1992 May;38(1-2):155-61
pubmed: 1315794
Adv Drug Deliv Rev. 2003 Nov 14;55(11):1515-24
pubmed: 14597144
Ann Neurol. 1994 May;35(5):592-7
pubmed: 7910004
J Leukoc Biol. 2000 Sep;68(3):423-8
pubmed: 10985260
Sci Rep. 2017 Jun 19;7(1):3759
pubmed: 28630405
J Acquir Immune Defic Syndr. 2019 Jul 1;81(3):274-283
pubmed: 30893126
Anal Chem. 2009 Jun 1;81(11):4356-68
pubmed: 19408941
Lipids. 1995 Dec;30(12):1127-35
pubmed: 8614303
J Neuroimmune Pharmacol. 2013 Dec;8(5):1136-46
pubmed: 24203462
Biochem Biophys Res Commun. 1998 Mar 27;244(3):819-24
pubmed: 9535750
Adv Nutr. 2020 Jul 1;11(4):760-772
pubmed: 32190891
Adv Drug Deliv Rev. 2020;159:198-213
pubmed: 31987838
Neurobiol Aging. 2000 May-Jun;21(3):383-421
pubmed: 10858586
CNS Neurosci Ther. 2016 Dec;22(12):943-951
pubmed: 27542570
Anal Bioanal Chem. 2015 Aug;407(21):6391-404
pubmed: 25935670
J Neurovirol. 2011 Feb;17(1):3-16
pubmed: 21174240
Neurology. 2016 Jan 26;86(4):334-40
pubmed: 26718568
Nature. 2014 May 22;509(7501):503-6
pubmed: 24828044
J Biol Chem. 2000 Jun 30;275(26):20146-56
pubmed: 10867029
Int Immunol. 2019 Aug 23;31(9):559-567
pubmed: 30772915
AIDS. 2004 Jan 1;18 Suppl 1:S79-86
pubmed: 15075502
J Neurochem. 2021 Jul;158(1):25-35
pubmed: 32402091
PLoS Comput Biol. 2007 Mar 23;3(3):e55
pubmed: 17381237
Nat Rev Immunol. 2015 Aug;15(8):511-23
pubmed: 26139350
Adv Biol Regul. 2017 Jan;63:15-21
pubmed: 27671966
Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12746-51
pubmed: 25139986
Ann Rheum Dis. 2003 Jun;62(6):501-9
pubmed: 12759283
Cell. 1993 Jan 29;72(2):269-78
pubmed: 8381049
Brain Pathol. 2005 Apr;15(2):159-66
pubmed: 15912889
Nature. 2014 May 22;509(7501):507-11
pubmed: 24828040
Front Immunol. 2018 Jan 29;9:38
pubmed: 29434586
BMC Infect Dis. 2013 May 04;13:203
pubmed: 23641933
J Clin Exp Neuropsychol. 2014;36(4):356-67
pubmed: 24645772
Sci Rep. 2020 Sep 3;10(1):14509
pubmed: 32884056
Biochim Biophys Acta. 1994 Oct 6;1214(3):303-8
pubmed: 7918613
Neuropsychol Rev. 2009 Jun;19(2):204-14
pubmed: 19430907
J Neurochem. 2005 Aug;94(3):850-61
pubmed: 16001969
Front Neurol. 2020 May 21;11:437
pubmed: 32528400
J Neural Transm (Vienna). 2000;107(8-9):1027-63
pubmed: 11041281
Cell Death Differ. 2007 Feb;14(2):296-305
pubmed: 16841089
Biochem Pharmacol. 2017 Dec 1;145:1-11
pubmed: 28647490
Retrovirology. 2012 Jan 11;9:4
pubmed: 22236409
Front Cell Neurosci. 2019 Jan 23;13:2
pubmed: 30728767
J Acquir Immune Defic Syndr. 2003 Jun 1;33 Suppl 2:S93-S105
pubmed: 12853858
Nature. 1994 Jan 13;367(6459):188-93
pubmed: 8114918
J Neurovirol. 2012 Aug;18(4):256-63
pubmed: 22528478
Signal Transduct Target Ther. 2021 Feb 26;6(1):94
pubmed: 33637672
J Acquir Immune Defic Syndr. 2018 Sep 1;79(1):101-107
pubmed: 29847476
Am J Pathol. 2010 Oct;177(4):1576-91
pubmed: 20813960
Neurology. 2017 Apr 4;88(14):1349-1357
pubmed: 28258081
J Neurovirol. 2002 Apr;8(2):136-42
pubmed: 11935465
Rapid Commun Mass Spectrom. 2008 Jul;22(13):2115-24
pubmed: 18523984
Prog Lipid Res. 2001 Jan-Mar;40(1-2):1-94
pubmed: 11137568
J Clin Exp Neuropsychol. 2011 Feb;33(2):200-9
pubmed: 20694873
Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):8212-6
pubmed: 10393974
Trends Mol Med. 2008 Oct;14(10):461-9
pubmed: 18774339
Neural Regen Res. 2021 Oct;16(10):2028-2029
pubmed: 33642390
Trends Immunol. 2002 Mar;23(3):144-50
pubmed: 11864843
Trends Pharmacol Sci. 2012 Jun;33(6):304-11
pubmed: 22464140
J Cereb Blood Flow Metab. 2011 Feb;31(2):486-93
pubmed: 20664612
Toxicol Lett. 2003 Apr 4;139(2-3):199-206
pubmed: 12628755
J Assoc Nurses AIDS Care. 2013 Mar-Apr;24(2):112-25
pubmed: 22943982
Neurology. 2007 May 1;68(18):1481-7
pubmed: 17470750
J Neuroinflammation. 2020 Jul 29;17(1):226
pubmed: 32727588
Future Lipidol. 2007 Aug;2(4):403-422
pubmed: 18176634
J Neuroimmune Pharmacol. 2012 Mar;7(1):60-73
pubmed: 21932048
J Immunol. 2014 Aug 15;193(4):1895-910
pubmed: 25031461
Nat Rev Neurol. 2016 May;12(5):309
pubmed: 27080521
Mol Biosyst. 2012 Apr;8(5):1585-94
pubmed: 22446875
Clin Infect Dis. 2015 Feb 1;60(3):473-80
pubmed: 25362201
J Exp Med. 1992 Dec 1;176(6):1703-18
pubmed: 1460427
Neurology. 2007 Dec 11;69(24):2213-20
pubmed: 17914066
Proc Natl Acad Sci U S A. 1989 Jan;86(2):621-5
pubmed: 2536171
Eur J Pharm Sci. 2018 Jun 5;121:356-381
pubmed: 29883727
Mediators Inflamm. 2020 Mar 25;2020:3267172
pubmed: 32308554
J Neurochem. 2000 Jul;75(1):196-203
pubmed: 10854262
AIDS. 2004 Jan 1;18 Suppl 1:S11-8
pubmed: 15075493
Brain Behav Immun. 2020 Oct;89:184-199
pubmed: 32534984
J Neurochem. 2007 Apr;101(1):57-76
pubmed: 17241120
J Neurochem. 2006 Jun;97(5):1288-300
pubmed: 16539649
J Neurochem. 2002 Aug;82(4):809-18
pubmed: 12358786
PLoS One. 2013 Aug 20;8(8):e74016
pubmed: 23977395
Front Pharmacol. 2022 Jan 26;13:781889
pubmed: 35153778
Pharmacol Res. 2019 Jan;139:182-190
pubmed: 30468889
Ann Neurol. 2004 Feb;55(2):257-67
pubmed: 14755730
Acta Neuropathol Commun. 2017 Jul 27;5(1):56
pubmed: 28750656
J Neurovirol. 2010 Nov;16(6):445-56
pubmed: 21087113
J Neurovirol. 2011 Jun;17(3):230-8
pubmed: 21491143
PLoS Biol. 2018 Aug 3;16(8):e2006443
pubmed: 30074985
J Immunol. 2010 Oct 15;185(8):4883-95
pubmed: 20855878
Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1671-5
pubmed: 1311847
J Acquir Immune Defic Syndr. 2019 Jun 1;81(2):216-223
pubmed: 30865184
J Neuroinflammation. 2011 Aug 16;8:101
pubmed: 21846384
Front Neurosci. 2016 Nov 08;10:488
pubmed: 27877101
Psychiatry Clin Neurosci. 2008 Oct;62(5):494-502
pubmed: 18950367
Front Neurol. 2020 Dec 01;11:581346
pubmed: 33335509
Eur J Neurosci. 1995 Dec 1;7(12):2502-7
pubmed: 8845955
Neurology. 2013 Oct 22;81(17):1492-9
pubmed: 24027056
Curr Colorectal Cancer Rep. 2012 Dec;8(4):316-324
pubmed: 23293573
Adv Nutr. 2016 Nov 15;7(6):1139-1141
pubmed: 28140331
J Biol Chem. 2001 Jun 22;276(25):22608-13
pubmed: 11319240
J Neuroimmunol. 2004 Dec;157(1-2):27-38
pubmed: 15579277
J Neurovirol. 2018 Apr;24(2):156-167
pubmed: 29075998
AIDS Behav. 2012 Nov;16(8):2279-85
pubmed: 22677976
Virology. 2000 Apr 10;269(2):294-304
pubmed: 10753708
Annu Rev Pathol. 2008;3:279-312
pubmed: 18233953
Neurobiol Aging. 2010 Mar;31(3):398-408
pubmed: 18547682