Glucocorticoid-induced leucine zipper (GILZ) in immuno suppression: master regulator or bystander?

Oncotarget. 2015 Nov 17;6(36):38446-57. doi: 10.18632/oncotarget.6197.

Abstract

Induction of glucocorticoid-induced leucine zipper (GILZ) by glucocorticoids has been reported to be essential for their anti-inflammatory actions. At the same time, GILZ is actively downregulated under inflammatory conditions, resulting in an enhanced pro-inflammatory response. Two papers published in the recent past showed elevated GILZ expression in the late stage of an inflammation. Still, the manuscripts suggest seemingly contradictory roles of endogenous GILZ: one of them suggested compensatory actions by elevated corticosterone levels in GILZ knockout mice, while our own manuscript showed a distinct phenotype upon GILZ knockout in vivo. Herein, we discuss the role of GILZ in inflammation with a special focus on the influence of endogenous GILZ on macrophage responses and suggest a cell-type specific action of GILZ as an explanation for the conflicting results as presented in recent reports.

Keywords: glucocorticoids; inflammation; lipopolysaccharide; macrophage; mouse models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Glucocorticoids / immunology
  • Glucocorticoids / pharmacology
  • Humans
  • Inflammation / immunology
  • Leucine Zippers / immunology*
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / pharmacology
  • Macrophages / immunology
  • Mice
  • Mice, Knockout
  • Transcription Factors / immunology*

Substances

  • Dsip1 protein, mouse
  • Glucocorticoids
  • Lipopolysaccharides
  • TSC22D3 protein, human
  • Transcription Factors