Glucocorticoid-induced leucine zipper promotes neutrophil and T-cell polarization with protective effects in acute kidney injury

Babak Baban, Cristina Marchetti, Hesam Khodadadi, Aneeq Malik, Golnaz Emami, Ping Chang Lin, Ali S. Arbab, Carlo Riccardi, Mahmood S. Mozaffari

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The glucocorticoid-induced leucine zipper (GILZ) mediates anti-inflammatory effects of glucocorticoids. Acute kidney injury (AKI) mobilizes immune/inflammatory mechanisms, causing tissue injury, but the impact of GILZ in AKI is not known. Neutrophils play context-specific proinflammatory [type 1 neutrophil (N1)] and anti-inflammatory [type 2 neutrophil (N2)] functional roles. Also, regulatory T lymphocytes (Tregs) and regulatory T-17 (Treg17) cells exert counterinflammatory effects, including the suppression of effector T lymphocytes [e.g., T-helper (Th) 17 cells]. Thus, utilizing cell preparations of mice kidneys subjected to AKI or sham operation, we determined the effects of GILZ on T cells and neutrophil subtypes in the context of its renoprotective effect; these studies used the transactivator of transcription (TAT)-GILZ or the TAT peptide. AKI increased N1 and Th-17 cells but reduced N2, Tregs, and Treg17 cells in association with increased interleukin (IL)-171 but reduced IL-101 cells accompanied with the disruption of mitochondrial membrane potential (ψm) and increased apoptosis/necrosis compared with sham kidneys. TAT-GILZ, compared with TAT, treatment reduced N1 and Th-17 cells but increased N2 and Tregs, without affecting Treg17 cells, in association with a reduction in IL-171 cells but an increase in IL-101 cells; TAT-GILZ caused less disruption of ψm and reduced cell death in AKI. Importantly, TAT-GILZ increased perfusion of the ischemic-reperfused kidney but reduced tissue edema compared with TAT. Utilizing splenic T cells and bone marrow–derived neutrophils, we further showed marked reduction in the proliferation of Th cells in response to TAT-GILZ compared with response to TAT. Collectively, the results indicate that GILZ exerts renoprotection accompanied by the upregulation of the regulatory/suppressive arm of immunity in AKI, likely via regulating cross talk between T cells and neutrophils.

Original languageEnglish (US)
Pages (from-to)483-493
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume367
Issue number3
DOIs
StatePublished - Dec 2018

Fingerprint

Leucine Zippers
Trans-Activators
Acute Kidney Injury
Glucocorticoids
Neutrophils
T-Lymphocytes
Interleukins
Regulatory T-Lymphocytes
Th17 Cells
Kidney
Anti-Inflammatory Agents
Mitochondrial Membrane Potential
Helper-Inducer T-Lymphocytes
Immunity
Edema
Cell Death
Necrosis
Up-Regulation
Perfusion
Apoptosis

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Glucocorticoid-induced leucine zipper promotes neutrophil and T-cell polarization with protective effects in acute kidney injury. / Baban, Babak; Marchetti, Cristina; Khodadadi, Hesam; Malik, Aneeq; Emami, Golnaz; Lin, Ping Chang; Arbab, Ali S.; Riccardi, Carlo; Mozaffari, Mahmood S.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 367, No. 3, 12.2018, p. 483-493.

Research output: Contribution to journalArticle

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abstract = "The glucocorticoid-induced leucine zipper (GILZ) mediates anti-inflammatory effects of glucocorticoids. Acute kidney injury (AKI) mobilizes immune/inflammatory mechanisms, causing tissue injury, but the impact of GILZ in AKI is not known. Neutrophils play context-specific proinflammatory [type 1 neutrophil (N1)] and anti-inflammatory [type 2 neutrophil (N2)] functional roles. Also, regulatory T lymphocytes (Tregs) and regulatory T-17 (Treg17) cells exert counterinflammatory effects, including the suppression of effector T lymphocytes [e.g., T-helper (Th) 17 cells]. Thus, utilizing cell preparations of mice kidneys subjected to AKI or sham operation, we determined the effects of GILZ on T cells and neutrophil subtypes in the context of its renoprotective effect; these studies used the transactivator of transcription (TAT)-GILZ or the TAT peptide. AKI increased N1 and Th-17 cells but reduced N2, Tregs, and Treg17 cells in association with increased interleukin (IL)-171 but reduced IL-101 cells accompanied with the disruption of mitochondrial membrane potential (ψm) and increased apoptosis/necrosis compared with sham kidneys. TAT-GILZ, compared with TAT, treatment reduced N1 and Th-17 cells but increased N2 and Tregs, without affecting Treg17 cells, in association with a reduction in IL-171 cells but an increase in IL-101 cells; TAT-GILZ caused less disruption of ψm and reduced cell death in AKI. Importantly, TAT-GILZ increased perfusion of the ischemic-reperfused kidney but reduced tissue edema compared with TAT. Utilizing splenic T cells and bone marrow–derived neutrophils, we further showed marked reduction in the proliferation of Th cells in response to TAT-GILZ compared with response to TAT. Collectively, the results indicate that GILZ exerts renoprotection accompanied by the upregulation of the regulatory/suppressive arm of immunity in AKI, likely via regulating cross talk between T cells and neutrophils.",
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AU - Malik, Aneeq

AU - Emami, Golnaz

AU - Lin, Ping Chang

AU - Arbab, Ali S.

AU - Riccardi, Carlo

AU - Mozaffari, Mahmood S.

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