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

ABSTRACT: 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 TNF? protein production in response to lipid A (LPA). In addition, mRNA expression of KC and IL-1? (Interleukin)-1? was decreased in CREB TG BMDMs; however, there was no difference in the mRNA expression of TNF?, 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 (NF?B) 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.

SUBMITTER: Wen AY

PROVIDER: S-EPMC3566130 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

Wen Andy Y AY Landaw Elliot M EM Ochoa Rachel R Cho Michelle M Chao Alex A Lawson Gregory G Sakamoto Kathleen M KM

PloS one 20130206 2

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) ...[more]

PMID: 23405224

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Project description:ImportanceSeveral studies reported an association between peritonsillar abscess formation and climate conditions, including seasonal changes; however, the results were inconsistent.ObjectiveTo evaluate the association between meteorological conditions and/or air pollution and peritonsillar abscess formation.Design, setting, and participantsIn this nested case-control study, 3819 participants with peritonsillar abscesses were matched (1:4) for age, sex, income, region of residence, hypertension, diabetes, and dyslipidemia with 15 276 control participants. The Korean Health Insurance Review and Assessment Service-National Sample Cohort (HIRA-NSC) data from 2002 through 2013 were used.Exposures and main outcomes and measuresThe meteorological data included the mean daily temperature (°C), highest daily temperature (°C), lowest daily temperature (°C), daily temperature difference (°C), relative humidity (%), spot atmospheric pressure (hPa), sulfur dioxide ([SO2], parts per million [ppm]), nitrogen dioxide (NO2, ppm), ozone (O3, ppm), carbon monoxide (CO, ppm), and particulate matter less than 10 μg (PM10, μg/m3) for the previous 14 days, 10 days, 7 days, 5 days, or 3 days before the matched index date. These factors were measured in 94 or 273 locations hourly. The crude and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of meteorological data for peritonsillar abscess formation were analyzed using unconditional logistic regression analysis. Subgroup analyses were conducted according to age and sex.ResultsThe male to female ratio of study participants was 1.43 (11 260 to 7835). Because the age groups were classified using 5-year intervals, the mean age could not be defined. The mean differences of NO2 and PM10 concentrations for the 14 days between peritonsillar abscess group and control group were 1.78 ppb (95% CI, 1.47-2.09) and 1.33 μg/m3 (95% CI, 0.67-1.99), respectively. The aORs of NO2 (0.1 ppm) and PM10 (10 μg/m3) during the 14 days prior to the index date for peritonsillar abscess formation were 12.8 (95% CI, 8.4-19.5) and 1.04 (95% CI, 1.02-1.06), respectively. The other meteorological conditions did not reach statistical significance.Conclusions and relevancePeritonsillar abscess formation was associated with high concentrations of NO2 and PM10.

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

Publications

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

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