The role of GILZ in modulation of adaptive immunity in a murine model of myocardial infarction

Experimental and Molecular Pathology
Babak BabanMahmood S Mozaffari

Abstract

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 paramete...Continue Reading

Citations

Oct 12, 2018·The Journal of Pharmacology and Experimental Therapeutics·Babak BabanMahmood S Mozaffari
Aug 24, 2019·Frontiers in Immunology·Lorenza CannarileEmira Ayroldi
Oct 4, 2020·The Journal of Pharmacology and Experimental Therapeutics·Mahmood Mozaffari
Nov 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Lisa K MullanyBert W O'Malley
Dec 20, 2020·Endocrinology·Lisa K MullanyBert W O'Malley
Feb 12, 2021·Endocrinology·Lisa K MullanyBert W O'Malley

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