HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Blockade of airway inflammation and hyperresponsiveness by inhibition of BLT2, a low-affinity leukotriene B4 receptor.

Abstract
BLT2 is a low-affinity receptor for leukotriene B(4) (LTB(4)), a potent lipid mediator of inflammation generated from arachidonic acid via the 5-lipoxygenase pathway. Unlike BLT1, a high-affinity receptor for LTB(4), 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. A murine 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, LTB(4), 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-kappaB, 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-kappaB"-linked inflammatory signaling pathway.
AuthorsKyung-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
JournalAmerican journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 42 Issue 3 Pg. 294-303 (Mar 2010) ISSN: 1535-4989 [Electronic] United States
PMID19448154 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • LTB4R protein, human
  • Ltb4r2 protein, mouse
  • NF-kappa B
  • RNA, Antisense
  • RNA, Messenger
  • Reactive Oxygen Species
  • Receptors, Leukotriene B4
  • Tetrazoles
  • Vascular Cell Adhesion Molecule-1
  • Ovalbumin
  • LY 255283
Topics
  • Animals
  • Asthma (genetics, physiopathology)
  • Biopsy
  • Bronchi (drug effects, pathology)
  • Bronchial Hyperreactivity (complications, pathology, physiopathology)
  • Cell Movement (drug effects)
  • Gene Expression Regulation (drug effects)
  • Humans
  • Lung (drug effects, pathology, physiopathology)
  • Mice
  • NF-kappa B (metabolism)
  • Ovalbumin
  • Pneumonia (complications, pathology, physiopathology)
  • RNA, Antisense (metabolism)
  • RNA, Messenger (genetics, metabolism)
  • Reactive Oxygen Species (metabolism)
  • Receptors, Leukotriene B4 (antagonists & inhibitors, genetics, metabolism)
  • Signal Transduction (drug effects)
  • T-Lymphocytes (cytology, drug effects)
  • Tetrazoles (pharmacology)
  • Vascular Cell Adhesion Molecule-1 (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: