PMID- 17575268
OWN - NLM
STAT- MEDLINE
DCOM- 20071025
LR  - 20091119
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 82
IP  - 3
DP  - 2007 Sep
TI  - Acute alcohol activates STAT3, AP-1, and Sp-1 transcription factors via the 
      family of Src kinases to promote IL-10 production in human monocytes.
PG  - 752-62
AB  - Alcohol consumption is associated with an imbalance in pro- and anti-inflammatory 
      cytokines and immunosuppression, partially as a result of enhanced IL-10 
      production. The mechanisms of IL-10 induction by alcohol remain poorly 
      understood. We identified that increased IL-10 production in human monocytes 
      after acute in vivo alcohol consumption or in vitro alcohol treatment was 
      associated with increased STAT3 activation. Alcohol alone induced and in 
      combination with LPS augmented STAT3 phosphorylation at tyrosine 705 (tyr705) and 
      serine 727 (ser727) residues and increased STAT3 binding to DNA. Upstream, 
      alcohol activated the Src kinases, as indicated by an increase in phosphorylated 
      and a decrease in nonphosphorylated Src proteins. STAT3 activation by Src kinases 
      occurred directly at the tyr705 residue and indirectly at the ser727 residue via 
      JNK MAPKs. Using specific Src (PP2), JNK1/2 (SB600125), or p38 (SB203580) 
      inhibitors, we determined that alcohol treatment alone induced and together with 
      LPS, augmented the DNA-binding capacity of the specificity protein-1 (Sp-1) and 
      AP-1 transcription factors involved in IL-10 production via Src-mediated 
      activation of p38 MAPK and JNK, respectively. Our data suggest that acute alcohol 
      activates Src/STAT3 and Src/MAPK/STAT3, AP-1, and Sp-1 pathways as important 
      mechanisms for IL-10-mediated immunomodulation after acute alcohol use.
FAU - Norkina, Oxana
AU  - Norkina O
AD  - University of Massachusetts Medical School, Department of Medicine, LRB 215, 364 
      Plantation Street, Worcester, MA 01605, USA.
FAU - Dolganiuc, Angela
AU  - Dolganiuc A
FAU - Shapiro, Taryn
AU  - Shapiro T
FAU - Kodys, Karen
AU  - Kodys K
FAU - Mandrekar, Pranoti
AU  - Mandrekar P
FAU - Szabo, Gyongyi
AU  - Szabo G
LA  - eng
GR  - AA008577/AA/NIAAA NIH HHS/United States
GR  - AA011576/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070615
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Alcohols)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Sp1 Transcription Factor)
RN  - 0 (Transcription Factor AP-1)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Alcohols/*pharmacology
MH  - Blotting, Western
MH  - Cell Nucleus/metabolism
MH  - Cells, Cultured
MH  - Cytoplasm/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Humans
MH  - Interleukin-10/*metabolism
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Male
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Monocytes/*metabolism
MH  - Phosphorylation
MH  - RNA, Messenger/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - STAT3 Transcription Factor/*metabolism
MH  - Signal Transduction
MH  - Sp1 Transcription Factor/*metabolism
MH  - Transcription Factor AP-1/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
MH  - src-Family Kinases/*metabolism
EDAT- 2007/06/19 09:00
MHDA- 2007/10/27 09:00
CRDT- 2007/06/19 09:00
PHST- 2007/06/19 09:00 [pubmed]
PHST- 2007/10/27 09:00 [medline]
PHST- 2007/06/19 09:00 [entrez]
AID - jlb.0207099 [pii]
AID - 10.1189/jlb.0207099 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2007 Sep;82(3):752-62. doi: 10.1189/jlb.0207099. Epub 2007 Jun 15.