Blockade of Airway Inflammation and Hyperresponsiveness by Inhibition of BLT2, a Low-Affinity Leukotriene B4 Receptor

Kyung Jin Cho, Ji Min Seo, YoungHyun Shin, Min Hyuk Yoo, Choon Sik Park, Shin Hwa Lee, Yoon Seok Chang, Sang Heon Cho, Jae-Hong Kim

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

BLT2 is a low-affinity receptor for leukotriene B4 (LTB 4), a potent lipid mediator of inflammation generated from arachidonic acid via the 5-lipoxygenase pathway. Unlike BLT1, a high-affinity receptor for LTB4, no clear physiological function has yet been identified for BLT2, especially with regard to the pathogenesis of asthma. The aim of this study was to investigate whether BLT2 plays a role in the pathogenesis of asthma. Amurine model of allergic asthma was used to evaluate the role of BLT2 in ovalbumin-induced airway inflammation and airway hyperresponsiveness. The levels of BLT2 mRNA and its ligand, LTB4, in the lung airway were highly elevated after ovalbumin challenge, and down-regulation of BLT2 with antisense BLT2 oligonucleotides markedly attenuated airway inflammation and airway hyperresponsiveness. Further analysis, aimed at identifying mediators downstream of BLT2, revealed that BLT2 activation led to elevation of reactive oxygen species and subsequent activation of NF-κB, thus inducing the expression of vascular cell adhesion molecule-1, which is known to be involved in eosinophil infiltration into the lung airway. Together, our results suggest that BLT2 plays a pivotal, mediatory role in the pathogenesis of asthma, acting through a "reactive oxygen species-NF-κB"-linked inflammatory signaling pathway.

Original languageEnglish
Pages (from-to)294-303
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume42
Issue number3
DOIs
Publication statusPublished - 2010 Mar 1

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Keywords

  • Asthma
  • BLT2
  • Inflammation
  • Lipid mediator
  • Reactive oxygen species

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

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