Exogenous IL-19 attenuates acute ischaemic injury and improves survival in male mice with myocardial infarction.
Animals
Cells, Cultured
Coronary Vessels
/ drug effects
Cytokines
/ genetics
Heart
/ drug effects
Heme Oxygenase-1
/ genetics
Macrophage Activation
/ drug effects
Male
Membrane Proteins
/ genetics
Mice, Inbred C57BL
Myocardial Infarction
/ drug therapy
Myocardium
/ metabolism
Neovascularization, Physiologic
/ drug effects
Receptors, Interleukin
/ metabolism
STAT3 Transcription Factor
/ metabolism
Vascular Endothelial Growth Factor A
/ metabolism
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
29
03
2018
revised:
21
10
2018
accepted:
24
10
2018
pubmed:
22
11
2018
medline:
6
5
2020
entrez:
22
11
2018
Statut:
ppublish
Résumé
Myocardial infarction (MI) is one of the leading causes of death in China and often results in the development of heart failure. In this work, we tested the therapeutic role of Interleukin-19 (IL-19) in mice with MI and investigated the underlying molecular mechanism. Mice were subjected to MI by ligation of left anterior descending coronary artery (LAD) and treated with IL-19 (10ng g Protein expression of IL-19 and its receptor in myocardium were upregulated 24 hrs post-MI in male mice. IL-19 treatment decreased infarct and apoptosis in myocardium, accompanied by enhanced haem oxygenase-1 (HO-1) activities and reduced malondialdehyde (MDA) formation. Pretreatment with IL-19 upregulated HO-1 expression in cultured neonatal mouse ventricular myocytes and attenuated oxygen-glucose deprivation (OGD)-induced injuries in vitro. Furthermore, IL-19 preserved cardiac function and improved survival of mice with MI. IL-19 reduced inflammatory infiltrates and suppressed formation of TNF-α, IL-1β, and IL-6. More importantly, IL-19 inhibited polarization toward proinflammatory M1 macrophages and stimulated M2 macrophage polarization in myocardium of mice with MI. IL-19 enhanced protein levels of vascular endothelial growth factor (VEGF) and promoted angiogenesis in myocardium of mice with MI. In addition, IL-19 treatment increased DNA-binding of the transcription factor STAT3 in myocardium of mice with MI. Treatment with exogenous IL-19 attenuated acute ischemic injury and improved survival of mice with MI. The mechanisms underlying these effects involved induction of HO-1, M2 macrophage polarization, angiogenesis, and STAT3 activation.
Sections du résumé
BACKGROUND AND PURPOSE
Myocardial infarction (MI) is one of the leading causes of death in China and often results in the development of heart failure. In this work, we tested the therapeutic role of Interleukin-19 (IL-19) in mice with MI and investigated the underlying molecular mechanism.
EXPERIMENTAL APPROACH
Mice were subjected to MI by ligation of left anterior descending coronary artery (LAD) and treated with IL-19 (10ng g
KEY RESULTS
Protein expression of IL-19 and its receptor in myocardium were upregulated 24 hrs post-MI in male mice. IL-19 treatment decreased infarct and apoptosis in myocardium, accompanied by enhanced haem oxygenase-1 (HO-1) activities and reduced malondialdehyde (MDA) formation. Pretreatment with IL-19 upregulated HO-1 expression in cultured neonatal mouse ventricular myocytes and attenuated oxygen-glucose deprivation (OGD)-induced injuries in vitro. Furthermore, IL-19 preserved cardiac function and improved survival of mice with MI. IL-19 reduced inflammatory infiltrates and suppressed formation of TNF-α, IL-1β, and IL-6. More importantly, IL-19 inhibited polarization toward proinflammatory M1 macrophages and stimulated M2 macrophage polarization in myocardium of mice with MI. IL-19 enhanced protein levels of vascular endothelial growth factor (VEGF) and promoted angiogenesis in myocardium of mice with MI. In addition, IL-19 treatment increased DNA-binding of the transcription factor STAT3 in myocardium of mice with MI.
CONCLUSIONS AND IMPLICATIONS
Treatment with exogenous IL-19 attenuated acute ischemic injury and improved survival of mice with MI. The mechanisms underlying these effects involved induction of HO-1, M2 macrophage polarization, angiogenesis, and STAT3 activation.
Identifiants
pubmed: 30460984
doi: 10.1111/bph.14549
pmc: PMC6365357
doi:
Substances chimiques
Cytokines
0
Membrane Proteins
0
Receptors, Interleukin
0
STAT3 Transcription Factor
0
Stat3 protein, mouse
0
Vascular Endothelial Growth Factor A
0
vascular endothelial growth factor A, mouse
0
Heme Oxygenase-1
EC 1.14.14.18
Hmox1 protein, mouse
EC 1.14.14.18
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
699-710Informations de copyright
© 2018 The British Pharmacological Society.
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