PMID- 23405224
OWN - NLM
STAT- MEDLINE
DCOM- 20130820
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 2
DP  - 2013
TI  - Increased abscess formation and defective chemokine regulation in CREB transgenic 
      mice.
PG  - e55866
LID - 10.1371/journal.pone.0055866 [doi]
LID - e55866
AB  - 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 TNFalpha protein production in response to lipid A (LPA). In addition, 
      mRNA expression of KC and IL-1beta (Interleukin)-1beta was decreased in CREB TG BMDMs; 
      however, there was no difference in the mRNA expression of TNFalpha, 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 (NFkappaB) 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.
FAU - Wen, Andy Y
AU  - Wen AY
AD  - Division of Critical Care, Department of Pediatrics, David Geffen School of 
      Medicine at University of California Los Angeles, Los Angeles, California, United 
      States of America.
FAU - Landaw, Elliot M
AU  - Landaw EM
FAU - Ochoa, Rachel
AU  - Ochoa R
FAU - Cho, Michelle
AU  - Cho M
FAU - Chao, Alex
AU  - Chao A
FAU - Lawson, Gregory
AU  - Lawson G
FAU - Sakamoto, Kathleen M
AU  - Sakamoto KM
LA  - eng
GR  - R01 HL075826/HL/NHLBI NIH HHS/United States
GR  - R41 HL078526/HL/NHLBI NIH HHS/United States
GR  - T32 HD007512/HD/NICHD NIH HHS/United States
GR  - HL78526/HL/NHLBI NIH HHS/United States
GR  - R01 HL097561/HL/NHLBI NIH HHS/United States
GR  - HL097561/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130206
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Chemokines)
RN  - 0 (Creb1 protein, mouse)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Cytokines)
SB  - IM
MH  - Abscess/diagnosis/*etiology
MH  - Animals
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Chemokines/genetics/*metabolism
MH  - Cyclic AMP Response Element-Binding Protein/*physiology
MH  - Cytokines/genetics/*metabolism
MH  - Female
MH  - Keratinocytes/metabolism/pathology
MH  - Macrophages/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Myeloid Cells/metabolism/*pathology
MH  - Neutrophils/metabolism/*pathology
MH  - Transcriptional Activation
PMC - PMC3566130
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/02/14 06:00
MHDA- 2013/08/21 06:00
PMCR- 2013/02/06
CRDT- 2013/02/14 06:00
PHST- 2012/09/03 00:00 [received]
PHST- 2013/01/03 00:00 [accepted]
PHST- 2013/02/14 06:00 [entrez]
PHST- 2013/02/14 06:00 [pubmed]
PHST- 2013/08/21 06:00 [medline]
PHST- 2013/02/06 00:00 [pmc-release]
AID - PONE-D-12-26481 [pii]
AID - 10.1371/journal.pone.0055866 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(2):e55866. doi: 10.1371/journal.pone.0055866. Epub 2013 Feb 6.