Inhibition of microsomal prostaglandin E synthase-1 ameliorates acute lung injury in mice.
BI 1029539
Celecoxib
GS-248
Leukocyte infiltration
Lung injury
Sepsis
Vascular permeability
mPGES-1
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
09 08 2021
09 08 2021
Historique:
received:
20
02
2021
accepted:
29
07
2021
entrez:
10
8
2021
pubmed:
11
8
2021
medline:
20
8
2021
Statut:
epublish
Résumé
To examine the effects of BI 1029539 (GS-248), a novel selective human microsomal prostaglandin E synthase-1 (mPGES-1) inhibitor, in experimental models of acute lung injury (ALI) and sepsis in transgenic mice constitutively expressing the mPGES1 (Ptges) humanized allele. Series 1: Lipopolysaccharide (LPS)-induced ALI. Mice were randomized to receive vehicle, BI 1029539, or celecoxib. Series 2: Cecal ligation and puncture-induced sepsis. Mice were randomized to receive vehicle or BI 1029539. Series 1: BI 1029539 or celecoxib reduced LPS-induced lung injury, with reduction in neutrophil influx, protein content, TNF-ɑ, IL-1β and PGE BI 1029539 ameliorates leukocyte infiltration and lung injury resulting from both endotoxin-induced and sepsis-induced lung injury.
Sections du résumé
BACKGROUND
To examine the effects of BI 1029539 (GS-248), a novel selective human microsomal prostaglandin E synthase-1 (mPGES-1) inhibitor, in experimental models of acute lung injury (ALI) and sepsis in transgenic mice constitutively expressing the mPGES1 (Ptges) humanized allele.
METHODS
Series 1: Lipopolysaccharide (LPS)-induced ALI. Mice were randomized to receive vehicle, BI 1029539, or celecoxib. Series 2: Cecal ligation and puncture-induced sepsis. Mice were randomized to receive vehicle or BI 1029539.
RESULTS
Series 1: BI 1029539 or celecoxib reduced LPS-induced lung injury, with reduction in neutrophil influx, protein content, TNF-ɑ, IL-1β and PGE
CONCLUSIONS
BI 1029539 ameliorates leukocyte infiltration and lung injury resulting from both endotoxin-induced and sepsis-induced lung injury.
Identifiants
pubmed: 34372885
doi: 10.1186/s12967-021-03016-9
pii: 10.1186/s12967-021-03016-9
pmc: PMC8351447
doi:
Substances chimiques
Tumor Necrosis Factor-alpha
0
Nitric Oxide Synthase Type II
EC 1.14.13.39
Cyclooxygenase 2
EC 1.14.99.1
Prostaglandin-E Synthases
EC 5.3.99.3
Dinoprostone
K7Q1JQR04M
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
340Informations de copyright
© 2021. The Author(s).
Références
Biol Pharm Bull. 2017;40(5):557-563
pubmed: 28458341
Expert Rev Clin Immunol. 2009 Jan 1;5(1):63-75
pubmed: 19885383
Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):9044-9
pubmed: 12835414
J Pharmacol Methods. 1985 Nov;14(3):157-67
pubmed: 2997548
Crit Care Clin. 2011 Apr;27(2):355-77
pubmed: 21440206
Prostaglandins Leukot Essent Fatty Acids. 2009 Jul;81(1):31-3
pubmed: 19524423
Inflamm Regen. 2011 Mar;31(2):157-166
pubmed: 22308189
Am J Physiol Regul Integr Comp Physiol. 2007 Jan;292(1):R258-67
pubmed: 16946079
Crit Care Med. 2015 Nov;43(11):e499-507
pubmed: 26468713
Crit Care Med. 2009 Jun;37(6):1994-9
pubmed: 19384202
Mol Med. 2011 Mar-Apr;17(3-4):293-307
pubmed: 21046059
Semin Respir Crit Care Med. 2006 Aug;27(4):337-49
pubmed: 16909368
J Lab Clin Med. 1998 Nov;132(5):414-20
pubmed: 9823935
J Neurosci. 2017 May 10;37(19):5035-5044
pubmed: 28438967
J Clin Invest. 2012 Aug;122(8):2731-40
pubmed: 22850883
Cell Death Dis. 2021 Feb 2;12(2):135
pubmed: 33542207
Blood. 2017 Feb 2;129(5):587-597
pubmed: 27827823
Pediatr Res. 2012 Nov;72(5):460-7
pubmed: 22926547
Clin Immunol. 2006 Jun;119(3):229-40
pubmed: 16540375
Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9894-9
pubmed: 17535900
Br J Pharmacol. 2017 Nov;174(22):4087-4098
pubmed: 28675448
Br J Pharmacol. 2019 Dec;176(24):4625-4638
pubmed: 31404942
Adv Pharmacol Sci. 2011;2011:254619
pubmed: 21738527
J Biol Chem. 2004 Aug 6;279(32):33684-95
pubmed: 15140897
Physiol Behav. 2009 Jun 22;97(3-4):279-92
pubmed: 19275907
J Allergy Clin Immunol. 2013 Feb;131(2):532-40.e1-2
pubmed: 22704539
Trends Cardiovasc Med. 2010 Aug;20(6):189-95
pubmed: 22137640
PLoS One. 2013 Oct 16;8(10):e77628
pubmed: 24147040
FASEB J. 2019 Dec;33(12):13966-13981
pubmed: 31638830
J Pathol. 2019 Apr;247(5):672-685
pubmed: 30570146
Int Immunol. 2019 Aug 23;31(9):597-606
pubmed: 30926983
Am J Respir Crit Care Med. 2006 May 15;173(10):1130-8
pubmed: 16514111
Biochem Pharmacol. 2015 Nov 1;98(1):1-15
pubmed: 26123522
Circulation. 2016 Jul 26;134(4):328-38
pubmed: 27440004
J Immunol. 2012 Apr 15;188(8):4093-102
pubmed: 22412193
Am J Physiol Lung Cell Mol Physiol. 2006 May;290(5):L797-805
pubmed: 16603593
Future Med Chem. 2011 Nov;3(15):1909-34
pubmed: 22023034
Am J Respir Crit Care Med. 1994 Jul;150(1):113-22
pubmed: 8025736
J Pharmacol Exp Ther. 2008 Sep;326(3):754-63
pubmed: 18524979
N Engl J Med. 2005 Mar 17;352(11):1092-102
pubmed: 15713943
J Infect Dis. 2016 Feb 15;213(4):532-40
pubmed: 26310310
Prostaglandins Other Lipid Mediat. 2009 Nov;90(1-2):21-5
pubmed: 19559811