Vitronectin-derived bioactive peptide prevents spondyloarthritis by modulating Th17/Treg imbalance in mice with curdlan-induced spondyloarthritis.
Animals
Celecoxib
/ administration & dosage
Cytokines
/ genetics
Disease Models, Animal
Disease Progression
Female
Gene Expression Regulation
/ drug effects
Humans
Integrin alphaVbeta3
/ metabolism
Integrin beta1
/ metabolism
Mice
Peptides
/ administration & dosage
STAT3 Transcription Factor
/ genetics
Signal Transduction
Spleen
/ immunology
Spondylarthritis
/ chemically induced
T-Lymphocytes, Regulatory
/ metabolism
Th17 Cells
/ metabolism
Vitronectin
/ chemistry
beta-Glucans
/ adverse effects
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2022
2022
Historique:
received:
12
10
2021
accepted:
17
12
2021
entrez:
5
1
2022
pubmed:
6
1
2022
medline:
19
2
2022
Statut:
epublish
Résumé
Spondyloarthritis (SpA) is a systemic inflammatory arthritis mediated mainly by interleukin (IL)-17. The vitronectin-derived bioactive peptide, VnP-16, exerts an anti-osteoporotic effect via β1 and αvβ3 integrin signaling. SpA is associated with an increased risk of osteoporosis, and we investigated the effect of VnP-16 in mice with SpA. SpA was induced by curdlan in SKG ZAP-70W163C mice, which were treated with vehicle, celecoxib, VnP-16, or VnP-16+celecoxib. The clinical score, arthritis score, spondylitis score, and proinflammatory cytokine expression of the spine were evaluated by immunohistochemical staining. Type 17 helper T cell (Th17) and regulatory T cell (Treg) differentiation in the spleen was evaluated by flow cytometry and in the spine by confocal staining. Splenocyte expression of signal transducer and activator of transcription (STAT) 3 and pSTAT3 was evaluated by in vitro Western blotting. The clinical score was significantly reduced in the VnP16+celecoxib group. The arthritis and spondylitis scores were significantly lower in the VnP-16 and VnP16+celecoxib groups than the vehicle group. In the spine, the levels of IL-1β, IL-6, tumor necrosis factor-α, and IL-17 expression were reduced and Th17/Treg imbalance was regulated in the VnP-16 alone and VnP-16+celecoxib groups. Flow cytometry of splenocytes showed increased polarization of Tregs in the VnP-16+celecoxib group. In vitro, VnP-16 suppressed pSTAT3. VnP-16 plus celecoxib prevented SpA progression in a mouse model by regulating the Th17/Treg imbalance and suppressing the expression of proinflammatory cytokines.
Identifiants
pubmed: 34986165
doi: 10.1371/journal.pone.0262183
pii: PONE-D-21-32711
pmc: PMC8730421
doi:
Substances chimiques
Cytokines
0
Integrin alphaVbeta3
0
Integrin beta1
0
Peptides
0
STAT3 Transcription Factor
0
Stat3 protein, mouse
0
Vitronectin
0
beta-Glucans
0
curdlan
6930DL209R
Celecoxib
JCX84Q7J1L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0262183Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Rheumatology (Oxford). 2021 Aug 2;60(8):3923-3935
pubmed: 33237331
J Exp Med. 2007 Jan 22;204(1):41-7
pubmed: 17227914
J Clin Immunol. 2013 Jan;33(1):151-61
pubmed: 22926407
Eur J Immunol. 2015 May;45(5):1426-40
pubmed: 25689841
Arthritis Rheumatol. 2014 Feb;66(2):231-41
pubmed: 24504793
Ann Rheum Dis. 2020 Oct;79(10):1327-1332
pubmed: 32660979
Arthritis Rheumatol. 2019 Oct;71(10):1599-1613
pubmed: 31436036
Ann Rheum Dis. 2009 Jun;68 Suppl 2:ii1-44
pubmed: 19433414
Nat Rev Immunol. 2008 Jul;8(7):523-32
pubmed: 18566595
J Transl Med. 2019 Jan 10;17(1):18
pubmed: 30630513
Ann Rheum Dis. 2019 Sep;78(9):1167-1178
pubmed: 31278139
Nat Rev Rheumatol. 2010 Jul;6(7):399-405
pubmed: 20517295
J Clin Invest. 2010 Dec;120(12):4445-52
pubmed: 21099114
Arthritis Rheum. 2012 Jul;64(7):2211-22
pubmed: 22328069
Cell Death Differ. 2018 Feb;25(2):268-281
pubmed: 28937683
J Immunol. 2018 Jun 15;200(12):4012-4023
pubmed: 29703862
Int J Mol Sci. 2018 Feb 06;19(2):
pubmed: 29415483
Osteoporos Int. 2011 Feb;22(2):421-33
pubmed: 20552328
J Rheumatol. 2010 Nov;37(11):2247-50
pubmed: 20889599
Ann Rheum Dis. 2005 Feb;64(2):338-9
pubmed: 15096328
Arthritis Rheum. 2005 Jun;52(6):1756-65
pubmed: 15934081
Arthritis Care Res (Hoboken). 2016 Sep;68(9):1320-31
pubmed: 26713432
Curr Opin Rheumatol. 2007 Jul;19(4):340-5
pubmed: 17551363
Arthritis Rheumatol. 2020 May;72(5):733-749
pubmed: 31960614
Curr Pharm Des. 2010;16(27):2950-60
pubmed: 20722616
Curr Rheumatol Rep. 2010 Oct;12(5):332-6
pubmed: 20680529
Rheumatology (Oxford). 2003 Aug;42(8):1018-20
pubmed: 12869678
J Transl Med. 2016 Jun 27;14(1):190
pubmed: 27350608
RMD Open. 2015 Jul 14;1(1):e000052
pubmed: 26509065
Arthritis Rheum. 2011 Oct;63(10):2939-48
pubmed: 21618207
Cell Rep. 2016 Aug 2;16(5):1339-1351
pubmed: 27452457
PLoS One. 2012;7(4):e31000
pubmed: 22485125
Nat Rev Dis Primers. 2015 Jul 09;1:15013
pubmed: 27188328
Med Res Rev. 2020 Jan;40(1):245-262
pubmed: 31215680
Ann Rheum Dis. 2018 Jan;77(1):63-69
pubmed: 28939631
Arthritis Res Ther. 2018 Jun 7;20(1):115
pubmed: 29880011
Front Med (Lausanne). 2019 Oct 04;6:214
pubmed: 31637243
Clin Rheumatol. 2019 Feb;38(2):465-475
pubmed: 30206711
Immune Netw. 2019 Feb 20;19(1):e2
pubmed: 30838157
Lancet. 1989 Dec 23-30;2(8678-8679):1483-5
pubmed: 2574769
Arthritis Rheumatol. 2019 Jan;71(1):82-90
pubmed: 29984487
Cancer Immunol Res. 2014 Apr;2(4):288-94
pubmed: 24764575
Cell. 2015 Sep 24;163(1):160-73
pubmed: 26406376
Ann Rheum Dis. 2019 Sep;78(9):1220-1225
pubmed: 31122911
Ann Rheum Dis. 2014 Oct;73(10):1819-25
pubmed: 23852807