Increased abscess formation and defective chemokine regulation in CREB transgenic mice.

Cyclic AMP-response element-binding protein (CREB) is a transcription factor implicated in growth factor-dependent cell proliferation and survival, glucose homeostasis, spermatogenesis, circadian rhythms, and synaptic plasticity associated with memory. To study the phenotype of CREB overexpression i...

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Autores principales: Andy Y Wen, Elliot M Landaw, Rachel Ochoa, Michelle Cho, Alex Chao, Gregory Lawson, Kathleen M Sakamoto
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/75548741c0c64e87a82a55f0799038bf
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spelling oai:doaj.org-article:75548741c0c64e87a82a55f0799038bf2021-11-18T07:58:30ZIncreased abscess formation and defective chemokine regulation in CREB transgenic mice.1932-620310.1371/journal.pone.0055866https://doaj.org/article/75548741c0c64e87a82a55f0799038bf2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23405224/?tool=EBIhttps://doaj.org/toc/1932-6203Cyclic AMP-response element-binding protein (CREB) is a transcription factor implicated in growth factor-dependent cell proliferation and survival, glucose homeostasis, spermatogenesis, circadian rhythms, and synaptic plasticity associated with memory. To study the phenotype of CREB overexpression in vivo, we generated CREB transgenic (TG) mice in which a myeloid specific hMRP8 promoter drives CREB expression. CREB TG mice developed spontaneous skin abscesses more frequently than wild type (WT) mice. To understand the role of CREB in myeloid function and innate immunity, chemokine expression in bone marrow derived macrophages (BMDMs) from CREB TG mice were compared with BMDMs from WT mice. Our results demonstrated decreased Keratinocyte-derived cytokine (KC) in CREB TG BMDMs but not TNFα protein production in response to lipid A (LPA). In addition, mRNA expression of KC and IL-1β (Interleukin)-1β was decreased in CREB TG BMDMs; however, there was no difference in the mRNA expression of TNFα, MCP-1, IL-6 and IL-12p40. The mRNA expression of IL-1RA and IL-10 was decreased in response to LPA. Nuclear factor kappa B (NFκB) expression and a subset of its target genes were upregulated in CREB TG mouse BMDMs. Although neutrophil migration was the same in both CREB TG and WT mice, Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was significantly increased in neutrophils from CREB TG mice. Taken together, CREB overexpression in myeloid cells results in increased abscess formation in vivo and aberrant cytokine and chemokine response, and neutrophil function in vitro.Andy Y WenElliot M LandawRachel OchoaMichelle ChoAlex ChaoGregory LawsonKathleen M SakamotoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e55866 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Andy Y Wen
Elliot M Landaw
Rachel Ochoa
Michelle Cho
Alex Chao
Gregory Lawson
Kathleen M Sakamoto
Increased abscess formation and defective chemokine regulation in CREB transgenic mice.
description Cyclic AMP-response element-binding protein (CREB) is a transcription factor implicated in growth factor-dependent cell proliferation and survival, glucose homeostasis, spermatogenesis, circadian rhythms, and synaptic plasticity associated with memory. To study the phenotype of CREB overexpression in vivo, we generated CREB transgenic (TG) mice in which a myeloid specific hMRP8 promoter drives CREB expression. CREB TG mice developed spontaneous skin abscesses more frequently than wild type (WT) mice. To understand the role of CREB in myeloid function and innate immunity, chemokine expression in bone marrow derived macrophages (BMDMs) from CREB TG mice were compared with BMDMs from WT mice. Our results demonstrated decreased Keratinocyte-derived cytokine (KC) in CREB TG BMDMs but not TNFα protein production in response to lipid A (LPA). In addition, mRNA expression of KC and IL-1β (Interleukin)-1β was decreased in CREB TG BMDMs; however, there was no difference in the mRNA expression of TNFα, MCP-1, IL-6 and IL-12p40. The mRNA expression of IL-1RA and IL-10 was decreased in response to LPA. Nuclear factor kappa B (NFκB) expression and a subset of its target genes were upregulated in CREB TG mouse BMDMs. Although neutrophil migration was the same in both CREB TG and WT mice, Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was significantly increased in neutrophils from CREB TG mice. Taken together, CREB overexpression in myeloid cells results in increased abscess formation in vivo and aberrant cytokine and chemokine response, and neutrophil function in vitro.
format article
author Andy Y Wen
Elliot M Landaw
Rachel Ochoa
Michelle Cho
Alex Chao
Gregory Lawson
Kathleen M Sakamoto
author_facet Andy Y Wen
Elliot M Landaw
Rachel Ochoa
Michelle Cho
Alex Chao
Gregory Lawson
Kathleen M Sakamoto
author_sort Andy Y Wen
title Increased abscess formation and defective chemokine regulation in CREB transgenic mice.
title_short Increased abscess formation and defective chemokine regulation in CREB transgenic mice.
title_full Increased abscess formation and defective chemokine regulation in CREB transgenic mice.
title_fullStr Increased abscess formation and defective chemokine regulation in CREB transgenic mice.
title_full_unstemmed Increased abscess formation and defective chemokine regulation in CREB transgenic mice.
title_sort increased abscess formation and defective chemokine regulation in creb transgenic mice.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/75548741c0c64e87a82a55f0799038bf
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