The inhibition of TNF-α-induced E-selectin expression in endothelial cells via the JNK/NF-κB pathways by highly N-acetylated chitooligosaccharides

Chia Wen Lin, Li Jing Chen, Pei Ling Lee, Chih I. Lee, Jui Che Lin, Jeng Jiann Chiu

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Chitooligosaccharides (COS) have been shown to regulate various cellular and biological functions. However, the effect of COS on inflammatory responses of the cells remains unclear. We investigated the regulatory effect of highly N-acetylated COS (NACOS) on tumor necrosis factor-α (TNF-α)-induced endothelial cell (EC) E-selectin expression, which is crucial for leukocyte recruitment. ECs were kept as controls or pre-treated with NACOS for different times, and then stimulated with TNF-α for 4 h. The results show that pre-treating ECs with NACOS inhibited the TNF-α-induced E-selectin expression in a dose- and time-dependent manner. This NACOS-mediated inhibition in E-selectin expression was regulated at the transcriptional level, but not due to changes in mRNA stability. Stimulation of ECs with TNF-α-induced rapid increases in the phosphorylation of their mitogen-activated protein kinases (MAPKs) [extracellular signal-regulated kinase (ERK), c-Jun-NH2-terminal kinase (JNK), and p38 MAPK]; the inhibitor for JNK (i.e., SP600125), but not those for ERK (i.e., PD98059) and p38 MAPK (i.e., SB203580), attenuated this TNF-α-induced E-selectin expression. Pre-treating ECs with NACOS inhibited the TNF-α-induced JNK activation, suggesting that JNK was involved in the inhibitory effect of NACOS on TNF-α-induced E-selectin expression. Pre-treating ECs with NACOS inhibited the TNF-α-induced p65 and p50 mRNA expressions. Gel shifting and chromatin immunoprecipitation assays showed that NACOS blocked the TNF-α-induced increases in the binding activity and in vivo promoter binding of nuclear factor-κB (NF-κB) in ECs. Our findings provide a molecular mechanism by which NACOS inhibit TNF-α-induced E-selectin expression in ECs, and a basis for using NACOS in pharmaceutical therapy against inflammation.

Original languageEnglish
Pages (from-to)1355-1366
Number of pages12
JournalBiomaterials
Volume28
Issue number7
DOIs
Publication statusPublished - Mar 1 2007
Externally publishedYes

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Keywords

  • Cell signaling
  • Chitin/chitosan
  • Endothelial cell
  • Gene expression
  • Inflammation

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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