Topical Application of the PI3Kβ-Selective Small Molecule Inhibitor TGX-221 Is an Effective Treatment Option for Experimental Epidermolysis Bullosa Acquisita.
PI3K
bullous skin diseases
immune-complex induced autoimmunity
neutrophils
signaling
Journal
Frontiers in medicine
ISSN: 2296-858X
Titre abrégé: Front Med (Lausanne)
Pays: Switzerland
ID NLM: 101648047
Informations de publication
Date de publication:
2021
2021
Historique:
received:
22
05
2021
accepted:
17
08
2021
entrez:
24
9
2021
pubmed:
25
9
2021
medline:
25
9
2021
Statut:
epublish
Résumé
Class I phosphoinositide 3-kinases (PI3K) have been implemented in pathogenesis of experimental epidermolysis bullosa acquisita (EBA), an autoimmune skin disease caused by type VII collagen (COL7) autoantibodies. Mechanistically, inhibition of specific PI3K isoforms, namely PI3Kβ or PI3Kδ, impaired immune complex (IC)-induced neutrophil activation, a key prerequisite for EBA pathogenesis. Data unrelated to EBA showed that neutrophil activation is also modulated by PI3Kα and γ, but their impact on the EBA has, so far, remained elusive. To address this and to identify potential therapeutic targets, we evaluated the impact of a panel of PI3K isoform-selective inhibitors (PI3Ki) on neutrophil function
Identifiants
pubmed: 34557502
doi: 10.3389/fmed.2021.713312
pmc: PMC8452940
doi:
Types de publication
Journal Article
Langues
eng
Pagination
713312Informations de copyright
Copyright © 2021 Zillikens, Kasprick, Osterloh, Gross, Radziewitz, Hass, Hartmann, Behnen-Härer, Ernst, Boch, Vidarsson, Visser, Laskay, Yu, Petersen, Ludwig and Bieber.
Déclaration de conflit d'intérêts
RL has received honoraria and research grants from the following companies: Admirx, Almirall, Amryth, ArgenX, Biotest, Biogen, Euroimmun, Incyte, Immungenetics, Lilly, Novartis, UCB Pharma, Topadur, True North Therapeutics, and Tx Cell. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
J Leukoc Biol. 2006 Dec;80(6):1491-9
pubmed: 16997858
Sci Signal. 2016 Aug 16;9(441):ra82
pubmed: 27531651
J Immunol. 2003 Mar 1;170(5):2647-54
pubmed: 12594293
Acta Derm Venereol. 2011 May;91(3):307-12
pubmed: 21394418
Science. 2000 Feb 11;287(5455):1040-6
pubmed: 10669416
Nature. 2004 Oct 21;431(7011):1007-11
pubmed: 15496927
J Pathol. 2012 Sep;228(1):8-19
pubmed: 22430937
Blood. 2004 May 1;103(9):3448-56
pubmed: 14751923
Blood. 2005 Aug 15;106(4):1432-40
pubmed: 15878979
J Immunol. 2015 Apr 15;194(8):3656-63
pubmed: 25795756
J Invest Dermatol. 2002 Apr;118(4):664-71
pubmed: 11918714
Am J Pathol. 1989 Jul;135(1):21-5
pubmed: 2672824
J Biol Chem. 1999 Apr 16;274(16):10963-8
pubmed: 10196176
Orphanet J Rare Dis. 2018 Sep 4;13(1):153
pubmed: 30180870
Front Immunol. 2020 Jan 14;10:3012
pubmed: 31993051
Blood. 1956 May;11(5):436-54
pubmed: 13315506
J Cell Biol. 1988 Mar;106(3):761-71
pubmed: 2450098
Exp Dermatol. 2017 Dec;26(12):1163-1170
pubmed: 28833569
Nat Med. 2012 Oct;18(10):1560-9
pubmed: 22983395
J Leukoc Biol. 2010 Jun;87(6):1083-95
pubmed: 20200404
Nucleic Acids Res. 2019 Jul 2;47(W1):W199-W205
pubmed: 31114916
Blood. 2010 Mar 18;115(11):2203-13
pubmed: 20081091
J Invest Dermatol. 2015 Jun;135(6):1565-1573
pubmed: 25689103
Front Immunol. 2019 Jun 26;10:1477
pubmed: 31293600
Eur J Pharmacol. 2013 Oct 15;718(1-3):428-34
pubmed: 23978569
Immunol Rev. 2015 Nov;268(1):66-73
pubmed: 26497513
Nat Med. 2005 Sep;11(9):936-43
pubmed: 16127437
J Clin Oncol. 2017 Dec 10;35(35):3898-3905
pubmed: 28976790
Sci Rep. 2019 May 17;9(1):7509
pubmed: 31101835
J Biol Chem. 2007 Mar 2;282(9):6116-25
pubmed: 17197441
Thromb Res. 2011 Jun;127(6):560-4
pubmed: 21396684
J Biol Chem. 1997 Aug 1;272(31):19236-41
pubmed: 9235916
J Exp Med. 2002 Sep 16;196(6):753-63
pubmed: 12235209
Front Med (Lausanne). 2018 Aug 20;5:220
pubmed: 30177969
Sci Rep. 2013 Dec 11;3:3470
pubmed: 24326778
Curr Protoc Pharmacol. 2019 Mar;84(1):e55
pubmed: 30786171
Cancer Cell. 2009 May 5;15(5):429-40
pubmed: 19411071
Mol Cell Biol. 2002 Dec;22(24):8580-91
pubmed: 12446777
Lancet Oncol. 2018 Apr;19(4):486-496
pubmed: 29475723
Front Immunol. 2017 May 31;8:603
pubmed: 28620373
Cancer Chemother Pharmacol. 2015 Oct;76(4):751-60
pubmed: 26254025
J Med Chem. 2015 Jan 8;58(1):480-511
pubmed: 25469863
Mamm Genome. 2002 Mar;13(3):169-72
pubmed: 11919689
J Invest Dermatol. 2020 Dec;140(12):2408-2420
pubmed: 32450072
Lancet. 2013 Jan 26;381(9863):320-32
pubmed: 23237497
PLoS One. 2015 Feb 06;10(2):e0116250
pubmed: 25659107
J Clin Invest. 2005 Apr;115(4):870-8
pubmed: 15841176
J Cardiovasc Pharmacol. 2001 Jun;37(6):751-61
pubmed: 11392472
Curr Top Microbiol Immunol. 2010;346:183-202
pubmed: 20473789
Nat Rev Mol Cell Biol. 2012 Feb 23;13(3):195-203
pubmed: 22358332
Eur J Immunol. 2011 Jun;41(6):1709-19
pubmed: 21469098
Front Immunol. 2018 May 04;9:931
pubmed: 29780388
J Pathol. 2007 May;212(1):56-65
pubmed: 17380558
Cell Syst. 2018 Sep 26;7(3):347-350.e1
pubmed: 30172842
Nucleic Acids Res. 2019 Jan 8;47(D1):D607-D613
pubmed: 30476243
Front Immunol. 2018 Jul 12;9:1558
pubmed: 30050528
Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4330-5
pubmed: 9113989
Int J Hematol. 2000 Dec;72(4):391-8
pubmed: 11197203
Biomolecules. 2019 Aug 30;9(9):
pubmed: 31480354
J Immunol. 2006 Sep 1;177(5):3461-8
pubmed: 16920988
Front Med (Lausanne). 2019 Jan 10;5:362
pubmed: 30687710
Clin Exp Immunol. 2001 Apr;124(1):157-62
pubmed: 11359455
J Invest Dermatol. 2018 Sep;138(9):1990-1998
pubmed: 29559343
J Immunol. 2014 Aug 15;193(4):1600-8
pubmed: 25024393
Exp Dermatol. 2017 Dec;26(12):1179-1186
pubmed: 28266741
Sci Rep. 2016 Dec 05;6:38357
pubmed: 27917914
Front Immunol. 2018 Feb 15;9:249
pubmed: 29497423
Sci Signal. 2011 Apr 12;4(168):ra23
pubmed: 21487106
Anal Biochem. 2009 Apr 15;387(2):150-61
pubmed: 19344656