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

Babak Baban, Lin Yin, Xu Qin, Jun Yao Liu, Xingming Shi, Mahmood S. Mozaffari

Research output: Contribution to journalArticle

2 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)408-414
Number of pages7
JournalExperimental and Molecular Pathology
Volume102
Issue number3
DOIs
StatePublished - Jun 1 2017

Keywords

  • Cell death
  • Cytokines
  • GILZ
  • Mitochondria
  • Myocardial infarction
  • T cells

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Clinical Biochemistry

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