Macrophage activation and differentiation signals regulate schlafen-4 gene expression: evidence for Schlafen-4 as a modulator of myelopoiesis.

<h4>Background</h4>The ten mouse and six human members of the Schlafen (Slfn) gene family all contain an AAA domain. Little is known of their function, but previous studies suggest roles in immune cell development. In this report, we assessed Slfn regulation and function in macrophages,...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Wendy J van Zuylen, Valerie Garceau, Adi Idris, Kate Schroder, Katharine M Irvine, Jane E Lattin, Dmitry A Ovchinnikov, Andrew C Perkins, Andrew D Cook, John A Hamilton, Paul J Hertzog, Katryn J Stacey, Stuart Kellie, David A Hume, Matthew J Sweet
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2011
Materias:
R
Q
Acceso en línea:https://doaj.org/article/0e772b52cc8148969f6d70d48c2a29ad
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:0e772b52cc8148969f6d70d48c2a29ad
record_format dspace
spelling oai:doaj.org-article:0e772b52cc8148969f6d70d48c2a29ad2021-11-18T07:00:40ZMacrophage activation and differentiation signals regulate schlafen-4 gene expression: evidence for Schlafen-4 as a modulator of myelopoiesis.1932-620310.1371/journal.pone.0015723https://doaj.org/article/0e772b52cc8148969f6d70d48c2a29ad2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21249125/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The ten mouse and six human members of the Schlafen (Slfn) gene family all contain an AAA domain. Little is known of their function, but previous studies suggest roles in immune cell development. In this report, we assessed Slfn regulation and function in macrophages, which are key cellular regulators of innate immunity.<h4>Methodology/principal findings</h4>Multiple members of the Slfn family were up-regulated in mouse bone marrow-derived macrophages (BMM) by the Toll-like Receptor (TLR)4 agonist lipopolysaccharide (LPS), the TLR3 agonist Poly(I∶C), and in disease-affected joints in the collagen-induced model of rheumatoid arthritis. Of these, the most inducible was Slfn4. TLR agonists that signal exclusively through the MyD88 adaptor protein had more modest effects on Slfn4 mRNA levels, thus implicating MyD88-independent signalling and autocrine interferon (IFN)-β in inducible expression. This was supported by the substantial reduction in basal and LPS-induced Slfn4 mRNA expression in IFNAR-1⁻/⁻ BMM. LPS causes growth arrest in macrophages, and other Slfn family genes have been implicated in growth control. Slfn4 mRNA levels were repressed during macrophage colony-stimulating factor (CSF-1)-mediated differentiation of bone marrow progenitors into BMM. To determine the role of Slfn4 in vivo, we over-expressed the gene specifically in macrophages in mice using a csf1r promoter-driven binary expression system. Transgenic over-expression of Slfn4 in myeloid cells did not alter macrophage colony formation or proliferation in vitro. Monocyte numbers, as well as inflammatory macrophages recruited to the peritoneal cavity, were reduced in transgenic mice that specifically over-expressed Slfn4, while macrophage numbers and hematopoietic activity were increased in the livers and spleens.<h4>Conclusions</h4>Slfn4 mRNA levels were up-regulated during macrophage activation but down-regulated during differentiation. Constitutive Slfn4 expression in the myeloid lineage in vivo perturbs myelopoiesis. We hypothesise that the down-regulation of Slfn4 gene expression during macrophage differentiation is a necessary step in development of this lineage.Wendy J van ZuylenValerie GarceauAdi IdrisKate SchroderKatharine M IrvineJane E LattinDmitry A OvchinnikovAndrew C PerkinsAndrew D CookJohn A HamiltonPaul J HertzogKatryn J StaceyStuart KellieDavid A HumeMatthew J SweetPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 1, p e15723 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Wendy J van Zuylen
Valerie Garceau
Adi Idris
Kate Schroder
Katharine M Irvine
Jane E Lattin
Dmitry A Ovchinnikov
Andrew C Perkins
Andrew D Cook
John A Hamilton
Paul J Hertzog
Katryn J Stacey
Stuart Kellie
David A Hume
Matthew J Sweet
Macrophage activation and differentiation signals regulate schlafen-4 gene expression: evidence for Schlafen-4 as a modulator of myelopoiesis.
description <h4>Background</h4>The ten mouse and six human members of the Schlafen (Slfn) gene family all contain an AAA domain. Little is known of their function, but previous studies suggest roles in immune cell development. In this report, we assessed Slfn regulation and function in macrophages, which are key cellular regulators of innate immunity.<h4>Methodology/principal findings</h4>Multiple members of the Slfn family were up-regulated in mouse bone marrow-derived macrophages (BMM) by the Toll-like Receptor (TLR)4 agonist lipopolysaccharide (LPS), the TLR3 agonist Poly(I∶C), and in disease-affected joints in the collagen-induced model of rheumatoid arthritis. Of these, the most inducible was Slfn4. TLR agonists that signal exclusively through the MyD88 adaptor protein had more modest effects on Slfn4 mRNA levels, thus implicating MyD88-independent signalling and autocrine interferon (IFN)-β in inducible expression. This was supported by the substantial reduction in basal and LPS-induced Slfn4 mRNA expression in IFNAR-1⁻/⁻ BMM. LPS causes growth arrest in macrophages, and other Slfn family genes have been implicated in growth control. Slfn4 mRNA levels were repressed during macrophage colony-stimulating factor (CSF-1)-mediated differentiation of bone marrow progenitors into BMM. To determine the role of Slfn4 in vivo, we over-expressed the gene specifically in macrophages in mice using a csf1r promoter-driven binary expression system. Transgenic over-expression of Slfn4 in myeloid cells did not alter macrophage colony formation or proliferation in vitro. Monocyte numbers, as well as inflammatory macrophages recruited to the peritoneal cavity, were reduced in transgenic mice that specifically over-expressed Slfn4, while macrophage numbers and hematopoietic activity were increased in the livers and spleens.<h4>Conclusions</h4>Slfn4 mRNA levels were up-regulated during macrophage activation but down-regulated during differentiation. Constitutive Slfn4 expression in the myeloid lineage in vivo perturbs myelopoiesis. We hypothesise that the down-regulation of Slfn4 gene expression during macrophage differentiation is a necessary step in development of this lineage.
format article
author Wendy J van Zuylen
Valerie Garceau
Adi Idris
Kate Schroder
Katharine M Irvine
Jane E Lattin
Dmitry A Ovchinnikov
Andrew C Perkins
Andrew D Cook
John A Hamilton
Paul J Hertzog
Katryn J Stacey
Stuart Kellie
David A Hume
Matthew J Sweet
author_facet Wendy J van Zuylen
Valerie Garceau
Adi Idris
Kate Schroder
Katharine M Irvine
Jane E Lattin
Dmitry A Ovchinnikov
Andrew C Perkins
Andrew D Cook
John A Hamilton
Paul J Hertzog
Katryn J Stacey
Stuart Kellie
David A Hume
Matthew J Sweet
author_sort Wendy J van Zuylen
title Macrophage activation and differentiation signals regulate schlafen-4 gene expression: evidence for Schlafen-4 as a modulator of myelopoiesis.
title_short Macrophage activation and differentiation signals regulate schlafen-4 gene expression: evidence for Schlafen-4 as a modulator of myelopoiesis.
title_full Macrophage activation and differentiation signals regulate schlafen-4 gene expression: evidence for Schlafen-4 as a modulator of myelopoiesis.
title_fullStr Macrophage activation and differentiation signals regulate schlafen-4 gene expression: evidence for Schlafen-4 as a modulator of myelopoiesis.
title_full_unstemmed Macrophage activation and differentiation signals regulate schlafen-4 gene expression: evidence for Schlafen-4 as a modulator of myelopoiesis.
title_sort macrophage activation and differentiation signals regulate schlafen-4 gene expression: evidence for schlafen-4 as a modulator of myelopoiesis.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/0e772b52cc8148969f6d70d48c2a29ad
work_keys_str_mv AT wendyjvanzuylen macrophageactivationanddifferentiationsignalsregulateschlafen4geneexpressionevidenceforschlafen4asamodulatorofmyelopoiesis
AT valeriegarceau macrophageactivationanddifferentiationsignalsregulateschlafen4geneexpressionevidenceforschlafen4asamodulatorofmyelopoiesis
AT adiidris macrophageactivationanddifferentiationsignalsregulateschlafen4geneexpressionevidenceforschlafen4asamodulatorofmyelopoiesis
AT kateschroder macrophageactivationanddifferentiationsignalsregulateschlafen4geneexpressionevidenceforschlafen4asamodulatorofmyelopoiesis
AT katharinemirvine macrophageactivationanddifferentiationsignalsregulateschlafen4geneexpressionevidenceforschlafen4asamodulatorofmyelopoiesis
AT janeelattin macrophageactivationanddifferentiationsignalsregulateschlafen4geneexpressionevidenceforschlafen4asamodulatorofmyelopoiesis
AT dmitryaovchinnikov macrophageactivationanddifferentiationsignalsregulateschlafen4geneexpressionevidenceforschlafen4asamodulatorofmyelopoiesis
AT andrewcperkins macrophageactivationanddifferentiationsignalsregulateschlafen4geneexpressionevidenceforschlafen4asamodulatorofmyelopoiesis
AT andrewdcook macrophageactivationanddifferentiationsignalsregulateschlafen4geneexpressionevidenceforschlafen4asamodulatorofmyelopoiesis
AT johnahamilton macrophageactivationanddifferentiationsignalsregulateschlafen4geneexpressionevidenceforschlafen4asamodulatorofmyelopoiesis
AT pauljhertzog macrophageactivationanddifferentiationsignalsregulateschlafen4geneexpressionevidenceforschlafen4asamodulatorofmyelopoiesis
AT katrynjstacey macrophageactivationanddifferentiationsignalsregulateschlafen4geneexpressionevidenceforschlafen4asamodulatorofmyelopoiesis
AT stuartkellie macrophageactivationanddifferentiationsignalsregulateschlafen4geneexpressionevidenceforschlafen4asamodulatorofmyelopoiesis
AT davidahume macrophageactivationanddifferentiationsignalsregulateschlafen4geneexpressionevidenceforschlafen4asamodulatorofmyelopoiesis
AT matthewjsweet macrophageactivationanddifferentiationsignalsregulateschlafen4geneexpressionevidenceforschlafen4asamodulatorofmyelopoiesis
_version_ 1718424021792456704