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

Oxana Norkina, Angela Dolganiuc, Taryn Shapiro, Karen Kodys, Pranoti Mandrekar, G. Szabó

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)752-762
Number of pages11
JournalJournal of Leukocyte Biology
Volume82
Issue number3
DOIs
Publication statusPublished - Sep 1 2007

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Sp1 Transcription Factor
src-Family Kinases
Transcription Factor AP-1
Interleukin-10
Monocytes
Alcohols
Alcohol Drinking
Serine
Tyrosine
Proteins
Immunomodulation
DNA
p38 Mitogen-Activated Protein Kinases
Immunosuppression
Anti-Inflammatory Agents
Phosphorylation
Cytokines
Therapeutics

Keywords

  • Lyn
  • MAPK

ASJC Scopus subject areas

  • Cell Biology

Cite this

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. / Norkina, Oxana; Dolganiuc, Angela; Shapiro, Taryn; Kodys, Karen; Mandrekar, Pranoti; Szabó, G.

In: Journal of Leukocyte Biology, Vol. 82, No. 3, 01.09.2007, p. 752-762.

Research output: Contribution to journalArticle

Norkina, Oxana ; Dolganiuc, Angela ; Shapiro, Taryn ; Kodys, Karen ; Mandrekar, Pranoti ; Szabó, G. / 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. In: Journal of Leukocyte Biology. 2007 ; Vol. 82, No. 3. pp. 752-762.
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