title: Aspirin treatment improved mesenchymal stem cell immunomodulatory properties via the 15d-PGJ2/PPARγ/TGF-β1 pathway.
abstract: Bone marrow mesenchymal stem cells (BMMSCs) have been used to treat a variety of autoimmune diseases in clinics. However, the therapeutic effects are largely dependent on the immunomodulatory capacity of culture-expanded BMMSCs. In the present study, we show that aspirin (acetylsalicylic acid, ASA)-treated BMMSCs have significantly improved immunomodulatory function, as indicated by upregulation of regulatory T cells (Tregs) and downregulation of Th17 cells via the 15d-PGJ2/PPARγ/TGF-β1 pathway. Furthermore, the therapeutic effect of ASA-pretreated BMMSCs was confirmed in a dextran sodium sulfate-induced experimental colitis mouse model, in which systemic infusion of ASA-pretreated BMMSCs significantly ameliorated disease activity index and colonic inflammation, along with an increased number of Tregs and decreased number of Th17 cells. Taken together, our results suggest that aspirin treatment is a feasible strategy to promote BMMSC-based immunomodulation.
authors.affiliation: 1 Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology , Beijing, People's Republic of China .
authors.forename: Jianxia
authors.initials: J
authors.lastname: Tang
authors.forename: Jimin
authors.initials: J
authors.lastname: Xiong
authors.forename: Tingting
authors.initials: T
authors.lastname: Wu
authors.forename: Zhangui
authors.initials: Z
authors.lastname: Tang
authors.forename: Gang
authors.initials: G
authors.lastname: Ding
authors.forename: Chunmei
authors.initials: C
authors.lastname: Zhang
authors.forename: Songlin
authors.initials: S
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001241:Aspirin / Q000494:pharmacology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003092:Colitis / Q000276:immunology / Q000628:therapy; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D056747:Immunomodulation / Q000187:drug effects*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: C477819:15-deoxyprostaglandin J2; D047495:PPAR gamma; D053773:Transforming Growth Factor beta1; D015232:Dinoprostone; D001241:Aspirin; D015230:Prostaglandin D2
references.citation: Cell Stem Cell. 2008 Feb 7;2(2):141-50
references.pmid: 18371435
references.citation: J Clin Periodontol. 2012 Dec;39(12):1174-82
references.pmid: 23005571
references.citation: Nat Med. 2011 Nov 20;17(12):1594-601
references.pmid: 22101767
references.citation: Pharmacology. 2005 Jun;74(3):152-6
references.pmid: 15775706
references.citation: Cell Immunol. 2012;273(1):30-40
references.pmid: 22196378
references.citation: Blood. 2007 Jan 1;109(1):228-34
references.pmid: 16985180
references.citation: Stem Cells. 2009 Jun;27(6):1421-32
references.pmid: 19489103
references.citation: Blood. 2012 Oct 11;120(15):3142-51
references.pmid: 22927248
references.citation: PLoS One. 2008 Jul 09;3(7):e2615
references.pmid: 18612428
references.citation: J Bone Miner Res. 2003 Oct;18(10):1795-802
references.pmid: 14584890
references.citation: Lancet. 2004 Jul 10-16;364(9429):149-55
references.pmid: 15246727
references.citation: Blood. 2001 Oct 15;98(8):2396-402
references.pmid: 11588036
references.citation: Inflamm Bowel Dis. 2009 Mar;15(3):341-52
references.pmid: 18942757
references.citation: Ann Rheum Dis. 2012 Oct;71(10):1733-40
references.pmid: 22586171
references.citation: Int J Biochem Cell Biol. 2012 Nov;44(11):2044-50
references.pmid: 22903019
references.citation: J Immunol. 2013 Mar 1;190(5):2372-80
references.pmid: 23359497
references.citation: Clin Immunol. 2011 Dec;141(3):328-37
references.pmid: 21944669
references.citation: Cell Stem Cell. 2012 May 4;10(5):544-55
references.pmid: 22542159
references.citation: ChemMedChem. 2009 Jun;4(6):939-45
references.pmid: 19301318
references.citation: Lancet. 2004 May 1;363(9419):1439-41
references.pmid: 15121408
references.citation: FASEB J. 2001 Aug;15(10):1822-4
references.pmid: 11481242
references.citation: Cell Prolif. 2009 Dec;42(6):721-30
references.pmid: 19706045
references.citation: J Cell Physiol. 2008 Feb;214(2):405-12
references.pmid: 17657727
references.citation: EMBO Mol Med. 2014 Mar;6(3):322-34
references.pmid: 24401839
references.citation: Immunology. 2000 Sep;101(1):53-60
references.pmid: 11012753
references.citation: Arthritis Rheum. 2011 Jun;63(6):1668-80
references.pmid: 21384335
references.citation: Diabetologia. 2009 Jul;52(7):1391-9
references.pmid: 19421731
references.citation: Cell Stem Cell. 2008 Apr 10;2(4):313-9
references.pmid: 18397751
references.citation: J Immunol. 2006 Jun 15;176(12):7761-7
references.pmid: 16751424
references.citation: Nat Med. 2003 Sep;9(9):1195-201
references.pmid: 12910262
references.citation: Stem Cells. 2013 Jul;31(7):1383-95
references.pmid: 23553791
references.citation: Trends Immunol. 2012 Mar;33(3):136-43
references.pmid: 22227317
references.citation: J Immunol. 2001 Jun 15;166(12):7053-62
references.pmid: 11390449
references.citation: Pediatr Res. 2012 Apr;71(4 Pt 2):445-51
references.pmid: 22430380
references.citation: Cell Res. 2013 Jan;23(1):107-21
references.pmid: 23266891
references.citation: Mol Pharmacol. 2006 Jul;70(1):415-25
references.pmid: 16611854
references.citation: Clin Exp Pharmacol Physiol. 2006 Aug;33(8):696-701
references.pmid: 16895542