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

doi:10.1371/journal.pone.0152385

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Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock

Journal article

Open access

Peer reviewed

Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock

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

PloS one, Vol.11(4), pp.e0152385-e0152385

2016

DOI: 10.1371/journal.pone.0152385

PMCID: PMC4817988

PMID: 27035130

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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 Toll-like 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 marrow-derived 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.

Neutrophils - cytology

Mice, Inbred C57BL

Cells, Cultured

NF-kappa B - immunology

Neutrophils - immunology

Male

Macrophages - cytology

Shock, Septic - immunology

Immunity, Innate

Chemotaxis

Lipopolysaccharides - immunology

Cell Migration Assays, Leukocyte

Interferon Regulatory Factors - immunology

Animals

Female

Mice

Immunity, Cellular

Macrophages - immunology

Cytokines - immunology

Details

Title: Subtitle: Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock
Creators: Sophie Joly - Department of Internal Medicine, The University of Iowa, Iowa City, IA, United States of America
Lindsey Rhea - Department of Pediatrics, The University of Iowa, Iowa City, IA, United States of America
Paige Volk - Department of Pediatrics, The University of Iowa, Iowa City, IA, United States of America
Jessica G Moreland - Department of Pediatrics, The University of Iowa, Iowa City, IA, United States of America
Martine Dunnwald - Department of Pediatrics, The University of Iowa, Iowa City, IA, United States of America
Resource Type: Journal article
Publication Details: PloS one, Vol.11(4), pp.e0152385-e0152385
DOI: 10.1371/journal.pone.0152385
PMID: 27035130
PMCID: PMC4817988
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: AR0615086 / NIAMS NIH HHS R01 AR067731 / NIAMS NIH HHS R03 AR061586 / NIAMS NIH HHS R01 AR067739 / NIAMS NIH HHS AR067731 / NIAMS NIH HHS
Language: English
Date published: 2016
Academic Unit: Anatomy and Cell Biology; Craniofacial Anomalies Research Center
Record Identifier: 9984025468402771

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