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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23405224/?tool=EBI |
| _version_ | 1828897694202986496 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T15:02:20Z |
| format | Article |
| id | doaj.art-75548741c0c64e87a82a55f0799038bf |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T15:02:20Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-75548741c0c64e87a82a55f0799038bf2022-12-21T23:41:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5586610.1371/journal.pone.0055866Increased abscess formation and defective chemokine regulation in CREB transgenic mice.Andy Y WenElliot M LandawRachel OchoaMichelle ChoAlex ChaoGregory LawsonKathleen M SakamotoCyclic 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23405224/?tool=EBI |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | Increased abscess formation and defective chemokine regulation in CREB transgenic mice. |
| title_sort | increased abscess formation and defective chemokine regulation in creb transgenic mice |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23405224/?tool=EBI |
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