Interferon Regulatory factor 6 has a protective role in the host response to endotoxic shock

Sophie Joly, Lindsey Rhea, Paige Volk, Jessica G. Moreland, Martine Dunnwald

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Interferon Regulatory Factor (IRF) 6, a member of the IRF family, is essential for epidermal and orofacial embryonic development. Irf6 is strongly expressed in keratinocytes, in which it regulates epidermal proliferation, differentiation, and migration. A recent role for Irf6 in Tolllike receptor 2-dependent chemokine gene expression was also reported in an epithelial cell line. However, a function for Irf6 in innate immune cells was not previously reported. In the present study, we investigated the expression and function of Irf6 in bone marrowderived neutrophils and macrophages. We show here, using a conditional knockout of Irf6 in lysosymeM expressing cells, that Irf6 is required for resistance to LPS-induced endotoxic shock. In addition, Irf6-deficient bone marrow-derived neutrophils exhibited increased chemotactic index and velocity compared with wild-type cells in vitro. TLR4-specific KC and IL6 secretions were upregulated in Irf6-deficient bone marrow-derived macrophages in vitro. These cells also exhibited an increased level of phosphorylated IkBa. Collectively, our findings suggest a role for Irf6 in the resistance to endotoxic shock due to NFk-B-mediated alteration of cytokine production.

Original languageEnglish (US)
Article numbere0152385
JournalPLoS One
Volume11
Issue number4
DOIs
StatePublished - Apr 1 2016

Fingerprint

Interferon Regulatory Factors
Septic Shock
Bone
Macrophages
bone marrow
neutrophils
macrophages
Neutrophils
cells
Chemokines
Gene expression
Interleukin-6
keratinocytes
chemokines
Keratinocytes
Cytokines
Embryonic Development
epithelial cells
cytokines
embryogenesis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Interferon Regulatory factor 6 has a protective role in the host response to endotoxic shock. / Joly, Sophie; Rhea, Lindsey; Volk, Paige; Moreland, Jessica G.; Dunnwald, Martine.

In: PLoS One, Vol. 11, No. 4, e0152385, 01.04.2016.

Research output: Contribution to journalArticle

@article{7beb328b579e4e7391dbc7d6d1c75741,
title = "Interferon Regulatory factor 6 has a protective role in the host response to endotoxic shock",
abstract = "Interferon Regulatory Factor (IRF) 6, a member of the IRF family, is essential for epidermal and orofacial embryonic development. Irf6 is strongly expressed in keratinocytes, in which it regulates epidermal proliferation, differentiation, and migration. A recent role for Irf6 in Tolllike receptor 2-dependent chemokine gene expression was also reported in an epithelial cell line. However, a function for Irf6 in innate immune cells was not previously reported. In the present study, we investigated the expression and function of Irf6 in bone marrowderived neutrophils and macrophages. We show here, using a conditional knockout of Irf6 in lysosymeM expressing cells, that Irf6 is required for resistance to LPS-induced endotoxic shock. In addition, Irf6-deficient bone marrow-derived neutrophils exhibited increased chemotactic index and velocity compared with wild-type cells in vitro. TLR4-specific KC and IL6 secretions were upregulated in Irf6-deficient bone marrow-derived macrophages in vitro. These cells also exhibited an increased level of phosphorylated IkBa. Collectively, our findings suggest a role for Irf6 in the resistance to endotoxic shock due to NFk-B-mediated alteration of cytokine production.",
author = "Sophie Joly and Lindsey Rhea and Paige Volk and Moreland, {Jessica G.} and Martine Dunnwald",
year = "2016",
month = "4",
day = "1",
doi = "10.1371/journal.pone.0152385",
language = "English (US)",
volume = "11",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

TY - JOUR

T1 - Interferon Regulatory factor 6 has a protective role in the host response to endotoxic shock

AU - Joly, Sophie

AU - Rhea, Lindsey

AU - Volk, Paige

AU - Moreland, Jessica G.

AU - Dunnwald, Martine

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Interferon Regulatory Factor (IRF) 6, a member of the IRF family, is essential for epidermal and orofacial embryonic development. Irf6 is strongly expressed in keratinocytes, in which it regulates epidermal proliferation, differentiation, and migration. A recent role for Irf6 in Tolllike receptor 2-dependent chemokine gene expression was also reported in an epithelial cell line. However, a function for Irf6 in innate immune cells was not previously reported. In the present study, we investigated the expression and function of Irf6 in bone marrowderived neutrophils and macrophages. We show here, using a conditional knockout of Irf6 in lysosymeM expressing cells, that Irf6 is required for resistance to LPS-induced endotoxic shock. In addition, Irf6-deficient bone marrow-derived neutrophils exhibited increased chemotactic index and velocity compared with wild-type cells in vitro. TLR4-specific KC and IL6 secretions were upregulated in Irf6-deficient bone marrow-derived macrophages in vitro. These cells also exhibited an increased level of phosphorylated IkBa. Collectively, our findings suggest a role for Irf6 in the resistance to endotoxic shock due to NFk-B-mediated alteration of cytokine production.

AB - Interferon Regulatory Factor (IRF) 6, a member of the IRF family, is essential for epidermal and orofacial embryonic development. Irf6 is strongly expressed in keratinocytes, in which it regulates epidermal proliferation, differentiation, and migration. A recent role for Irf6 in Tolllike receptor 2-dependent chemokine gene expression was also reported in an epithelial cell line. However, a function for Irf6 in innate immune cells was not previously reported. In the present study, we investigated the expression and function of Irf6 in bone marrowderived neutrophils and macrophages. We show here, using a conditional knockout of Irf6 in lysosymeM expressing cells, that Irf6 is required for resistance to LPS-induced endotoxic shock. In addition, Irf6-deficient bone marrow-derived neutrophils exhibited increased chemotactic index and velocity compared with wild-type cells in vitro. TLR4-specific KC and IL6 secretions were upregulated in Irf6-deficient bone marrow-derived macrophages in vitro. These cells also exhibited an increased level of phosphorylated IkBa. Collectively, our findings suggest a role for Irf6 in the resistance to endotoxic shock due to NFk-B-mediated alteration of cytokine production.

UR - http://www.scopus.com/inward/record.url?scp=84971323729&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84971323729&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0152385

DO - 10.1371/journal.pone.0152385

M3 - Article

VL - 11

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 4

M1 - e0152385

ER -