Platelet-activating factor and endotoxin activate CCAAT/enhancer binding protein in rat small intestine

Hao Wang, Xiaowu Qu, Isabelle G. De Plaen, Wei Hsueh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

1. The transcription factor family CCAAT/enhancer binding proteins (C/EBP) is involved in inflammation via the regulation of the gene expression of various pro-inflammatory cytokines and proteins. PAF and endotoxin (lipopolysaccharide, LPS) are known agents causing intestinal inflammation and injury. In this study, we examined the binding activity of C/EBP isoforms in rat small intestine in response to PAF (1.5 μg kg-1, i.v.) or LPS (5 mg kg-1, i.v.). 2. We found that C/EBP is constitutively active in normal small intestine, mainly as C/EBP-α and β (C/EBP-β > α). Both C/EBP-α and β are localized in the intestinal epithelial cells: C/EBP-α mainly in the crypts, and C/EBP-β in both villi and crypts, as well as in some lamina propria cells. Only minute amounts of C/EBP-δ were found. 3. PAF rapidly upregulates the binding activity of C/EBP-α and β within 30 min. The increase in C/EBP-α is prominent in the crypt cells, whereas the change of C/EBP-β is more widespread. LPS also increases the binding activity of C/EBP-α and β, and the response is slower than PAF. PAF synergizes with LPS to markedly activate all three subunits. The increase in C/EBP-α is transient, whereas the other two have a sustained elevation until 120 min. 4. After challenge with PAF (but not LPS), small amounts of nuclear factor -κB (NF-κB) p50 and p65 subunits are found in the C/EBP-DNA binding complex, indicating cross-dimerization of the two transcription families. Pretreatment of rats with pyrrolidine dithiocarbamate (PDTC) suppresses LPS-, but not PAF-, induced NF-κB and C/EBP binding activity, and significantly increases the C/EBP-δ subunit in LPS- or PAF-induced C/EBP complex. S These results suggest that PAF and LPS activate intestinal C/EBP in vivo, probably via different pathways.

Original languageEnglish (US)
Pages (from-to)713-721
Number of pages9
JournalBritish journal of pharmacology
Volume133
Issue number5
DOIs
StatePublished - 2001

Keywords

  • CCAAT/enhancer binding proteins
  • Endotoxin
  • Intestines
  • Lipopolysaccharide
  • NF-kappa B
  • Platelet activating factor
  • Rat
  • Transcription factors

ASJC Scopus subject areas

  • Pharmacology

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