TY - JOUR
T1 - The role of GILZ in modulation of adaptive immunity in a murine model of myocardial infarction
AU - Baban, Babak
AU - Yin, Lin
AU - Qin, Xu
AU - Liu, Jun Yao
AU - Shi, Xingming
AU - Mozaffari, Mahmood S.
N1 - Publisher Copyright:
© 2017
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Myocardial infarction (MI) is associated with intense immune and inflammatory responses which contribute to tissue injury. Increasing evidence indicates that the glucocorticoid-induced leucine zipper (GILZ) protein suppresses immune and inflammatory responses. However, the status of and the role of GILZ in MI are not known. We tested the hypotheses that a) MI reduces cardiac GILZ associated with intense inflammation and cell death and b) intramyocardial GILZ delivery confers cardioprotection in association with increased Tregs and suppression of inflammation. Male Balb/C mice were subjected to MI or sham operation; the infarcted animals were subdivided to receive intramyocardial injections of PBS, GILZ overexpressing cells (GILZ) or their controls expressing the green fluorescent protein (GFP). Three hours after the procedures, hearts were procured for subsequent analyses. MI markedly reduced cardiac GILZ expression accompanied with a) increase in Th-17 cells (i.e., CD3+ CD4+ IL-17+ BNP−) but decrease in Tregs (i.e., CD3+ CD4+ FoxP3+ BNP−), and b) disruption of mitochondrial membrane potential (ψm) associated with significant increases in apoptotic and necrotic cell death. While both GILZ and GFP returned the aforementioned parameters towards those of sham controls, these effects were most marked for mice receiving GILZ. Thus, GILZ markedly reduced Th-17 cells but increased Tregs and the anti-inflammatory cytokine, IL-10 positive cells accompanied with preservation of ψm and prevention of cell death. To our knowledge, this is the first report indicating an important role for GILZ in MI, in part via modulation of adaptive immune response, which raises the prospect of exogenous GILZ delivery as a novel cardioprotective modality.
AB - Myocardial infarction (MI) is associated with intense immune and inflammatory responses which contribute to tissue injury. Increasing evidence indicates that the glucocorticoid-induced leucine zipper (GILZ) protein suppresses immune and inflammatory responses. However, the status of and the role of GILZ in MI are not known. We tested the hypotheses that a) MI reduces cardiac GILZ associated with intense inflammation and cell death and b) intramyocardial GILZ delivery confers cardioprotection in association with increased Tregs and suppression of inflammation. Male Balb/C mice were subjected to MI or sham operation; the infarcted animals were subdivided to receive intramyocardial injections of PBS, GILZ overexpressing cells (GILZ) or their controls expressing the green fluorescent protein (GFP). Three hours after the procedures, hearts were procured for subsequent analyses. MI markedly reduced cardiac GILZ expression accompanied with a) increase in Th-17 cells (i.e., CD3+ CD4+ IL-17+ BNP−) but decrease in Tregs (i.e., CD3+ CD4+ FoxP3+ BNP−), and b) disruption of mitochondrial membrane potential (ψm) associated with significant increases in apoptotic and necrotic cell death. While both GILZ and GFP returned the aforementioned parameters towards those of sham controls, these effects were most marked for mice receiving GILZ. Thus, GILZ markedly reduced Th-17 cells but increased Tregs and the anti-inflammatory cytokine, IL-10 positive cells accompanied with preservation of ψm and prevention of cell death. To our knowledge, this is the first report indicating an important role for GILZ in MI, in part via modulation of adaptive immune response, which raises the prospect of exogenous GILZ delivery as a novel cardioprotective modality.
KW - Cell death
KW - Cytokines
KW - GILZ
KW - Mitochondria
KW - Myocardial infarction
KW - T cells
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UR - http://www.scopus.com/inward/citedby.url?scp=85019150965&partnerID=8YFLogxK
U2 - 10.1016/j.yexmp.2017.05.002
DO - 10.1016/j.yexmp.2017.05.002
M3 - Article
C2 - 28499885
AN - SCOPUS:85019150965
SN - 0014-4800
VL - 102
SP - 408
EP - 414
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
IS - 3
ER -