PMID- 32413484
OWN - NLM
STAT- MEDLINE
DCOM- 20210604
LR  - 20210604
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 158
DP  - 2020 Aug
TI  - Glucocorticoid-induced leucine zipper modulates macrophage polarization and 
      apoptotic cell clearance.
PG  - 104842
LID - S1043-6618(20)31150-6 [pii]
LID - 10.1016/j.phrs.2020.104842 [doi]
AB  - Macrophages are professional phagocytes that display remarkable plasticity, with 
      a range of phenotypes that can be broadly characterized by the M1/M2 dichotomy. 
      Glucocorticoid (GC)-induced leucine zipper (GILZ) is a protein known to mediate 
      anti-inflammatory and some pro-resolving actions, including as neutrophil 
      apoptosis. However, the role of GILZ in key macrophage function is not well 
      understood. Here, we investigated the role of GILZ on macrophage reprogramming 
      and efferocytosis. Using murine bone-marrow-derived macrophages (BMDMs), we found 
      that GILZ was expressed in naive BMDMs and exhibited increased expression in 
      M2-like macrophages (IL4-differentiated). M1-like macrophages 
      (IFN/LPS-differentiated) from GILZ(-/-) mice showed higher expression of the M1 
      markers CD86, MHC class II, iNOS, IL-6 and TNF-alpha, associated with increased 
      levels of phosphorylated STAT1 and lower IL-10 levels, compared to 
      M1-differentiated cells from WT mice. There were no changes in the M2 markers 
      CD206 and arginase-1 in macrophages from GILZ(-/-) mice differentiated with IL-4, 
      compared to cells from WT animals. Treatment of M1-like macrophages with 
      TAT-GILZ, a cell-permeable GILZ fusion protein, decreased the levels of CD86 and 
      MHC class II in M1-like macrophages without modifying CD206 levels in M2-like 
      macrophages. In line with the in vitro data, increased numbers of M1-like 
      macrophages were found into the pleural cavity of GILZ(-/-) mice after 
      LPS-injection, compared to WT mice. Moreover, efferocytosis was defective in the 
      context of GILZ deficiency, both in vitro and in vivo. Conversely, treatment of 
      LPS-injected mice with TAT-GILZ promoted inflammation resolution, associated with 
      lower numbers of M1-like macrophages and increased efferocytosis. Collectively, 
      these data indicate that GILZ is a regulator of important macrophage functions, 
      contributing to macrophage reprogramming and efferocytosis, both key steps for 
      the resolution of inflammation.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Vago, Juliana P
AU  - Vago JP
AD  - Departamento de Morfologia, Instituto de Ciencias Biologicas, Universidade 
      Federal de Minas Gerais, Belo Horizonte, Brazil; Departamento de Bioquimica e 
      Imunologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas 
      Gerais, Belo Horizonte, Brazil; Rheumatology Group, Centre for Inflammatory 
      Diseases, School of Clinical Sciences at Monash Health, Monash University, 
      Victoria, Australia.
FAU - Galvao, Izabela
AU  - Galvao I
AD  - Departamento de Morfologia, Instituto de Ciencias Biologicas, Universidade 
      Federal de Minas Gerais, Belo Horizonte, Brazil; Departamento de Bioquimica e 
      Imunologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas 
      Gerais, Belo Horizonte, Brazil.
FAU - Negreiros-Lima, Graziele L
AU  - Negreiros-Lima GL
AD  - Departamento de Analises Clinicas e Toxicologicas, Faculdade de Farmacia, 
      Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
FAU - Teixeira, Livia C R
AU  - Teixeira LCR
AD  - Departamento de Analises Clinicas e Toxicologicas, Faculdade de Farmacia, 
      Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
FAU - Lima, Katia M
AU  - Lima KM
AD  - Departamento de Analises Clinicas e Toxicologicas, Faculdade de Farmacia, 
      Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
FAU - Sugimoto, Michelle A
AU  - Sugimoto MA
AD  - Departamento de Bioquimica e Imunologia, Instituto de Ciencias Biologicas, 
      Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
FAU - Moreira, Isabella Z
AU  - Moreira IZ
AD  - Departamento de Analises Clinicas e Toxicologicas, Faculdade de Farmacia, 
      Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
FAU - Jones, Sarah A
AU  - Jones SA
AD  - Rheumatology Group, Centre for Inflammatory Diseases, School of Clinical Sciences 
      at Monash Health, Monash University, Victoria, Australia.
FAU - Lang, Tali
AU  - Lang T
AD  - Rheumatology Group, Centre for Inflammatory Diseases, School of Clinical Sciences 
      at Monash Health, Monash University, Victoria, Australia.
FAU - Riccardi, Carlo
AU  - Riccardi C
AD  - Departament of Medicine, Section of Pharmacology, University of Perugia, Perugia, 
      Italy.
FAU - Teixeira, Mauro M
AU  - Teixeira MM
AD  - Departamento de Morfologia, Instituto de Ciencias Biologicas, Universidade 
      Federal de Minas Gerais, Belo Horizonte, Brazil; Departamento de Bioquimica e 
      Imunologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas 
      Gerais, Belo Horizonte, Brazil.
FAU - Harris, James
AU  - Harris J
AD  - Rheumatology Group, Centre for Inflammatory Diseases, School of Clinical Sciences 
      at Monash Health, Monash University, Victoria, Australia.
FAU - Morand, Eric F
AU  - Morand EF
AD  - Rheumatology Group, Centre for Inflammatory Diseases, School of Clinical Sciences 
      at Monash Health, Monash University, Victoria, Australia.
FAU - Sousa, Lirlandia P
AU  - Sousa LP
AD  - Departamento de Analises Clinicas e Toxicologicas, Faculdade de Farmacia, 
      Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. Electronic address: 
      lipsousa72@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200513
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Dsip1 protein, mouse)
RN  - 0 (Glucocorticoids)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Bone Marrow Cells/drug effects
MH  - Cell Migration Assays, Leukocyte
MH  - Cell Physiological Phenomena/drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Glucocorticoids/*pharmacology
MH  - Inflammation/chemically induced/pathology
MH  - Leukocyte Count
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Pleural Cavity/cytology
MH  - Transcription Factors/*drug effects
OTO - NOTNLM
OT  - Efferocytosis
OT  - GILZ
OT  - Macrophage reprogramming
OT  - Resolution of inflammation
EDAT- 2020/05/16 06:00
MHDA- 2021/06/05 06:00
CRDT- 2020/05/16 06:00
PHST- 2019/11/13 00:00 [received]
PHST- 2020/04/07 00:00 [revised]
PHST- 2020/04/14 00:00 [accepted]
PHST- 2020/05/16 06:00 [pubmed]
PHST- 2021/06/05 06:00 [medline]
PHST- 2020/05/16 06:00 [entrez]
AID - S1043-6618(20)31150-6 [pii]
AID - 10.1016/j.phrs.2020.104842 [doi]
PST - ppublish
SO  - Pharmacol Res. 2020 Aug;158:104842. doi: 10.1016/j.phrs.2020.104842. Epub 2020 
      May 13.