Activation of ROS/NF-κB and Ca2+/CaM kinase II are necessary for VCAM-1 induction in IL-1β-treated human tracheal smooth muscle cells

Shue Fen Luo, Chia Chi Chang, I-Ta Lee, Chiang Wen Lee, Wei Ning Lin, Chih Chung Lin, Chuen Mao Yang

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Histone acetylation regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) plays a critical role in the expression of inflammatory genes, such as vascular cell adhesion molecule-1 (VCAM-1). Oxidative processes have been shown to induce VCAM-1 expression. Here, we investigated the mechanisms underlying IL-1β-induced VCAM-1 expression in human tracheal smooth muscle cells (HTSMCs). Our results showed that IL-1β enhanced HTSMCs-monocyte adhesion through up-regulation of VCAM-1, which was inhibited by pretreatment with selective inhibitors of PKCα (Gö6976), c-Src (PP1), NADPH oxidase [diphenylene iodonium (DPI) and apocynin (APO)], intracellular calcium chelator (BAPTA/AM), PI-PLC (U73122), CaM (calmidazolium chloride), CaM kinase II (KN62), p300 (garcinol), NF-κB (Bay11-7082), HDAC (trichostatin A), and ROS scavenger [N-acetyl-l-cysteine (NAC)] or transfection with siRNAs of MyD88, PKCα, Src, p47phox, p300, and HDAC4. Moreover, IL-1β stimulated NF-κB and CaMKII phosphorylation through MyD88-dependent PI-PLC/PKCα/c-Src/ROS and PI-PLC/Ca2+/CaM pathways, respectively. Activation of NF-κB and CaMKII may eventually lead to the acetylation of histone residues and phosphorylation of histone deacetylases. These findings suggested that IL-1β induced VCAM-1 expression via these multiple signaling pathways in HTSMCs. Blockade of these pathways may reduce monocyte adhesion via VCAM-1 suppression and attenuation of the inflammatory responses in airway diseases.

Original languageEnglish
Pages (from-to)8-21
Number of pages14
JournalToxicology and Applied Pharmacology
Volume237
Issue number1
DOIs
Publication statusPublished - May 15 2009
Externally publishedYes

Keywords

  • Cellular adhesion molecules
  • Cytokine
  • Histone acetyltransferases
  • Histone deacetylases
  • NADPH oxidase

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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