Cysteinyl leukotriene receptor antagonist regulates vascular permeability by reducing vascular endothelial growth factor expression.
BACKGROUND
Inflammation of the asthmatic airway is usually accompanied by increased vascular permeability and plasma exudation. Cysteinyl leukotrienes (cysLTs) potently elicit increased vascular permeability in airways, leading to airway edema. Vascular endothelial growth factor (VEGF) is 1 of the most potent proangiogenic cytokines and also increases vascular permeability so that plasma proteins can leak into the extravascular space. However, the mechanisms by which cysLTs induce increased vascular permeability are not clearly understood.


OBJECTIVE
An aim of the current study was to determine the role of the cysLTs, more specifically in the increase of vascular permeability.


METHODS
We used a BALB/c mouse model of allergic asthma to examine effects of cysLT receptor antagonists on bronchial inflammation and airway hyperresponsiveness, more specifically on the increase of vascular permeability.


RESULTS
These mice develop the following typical pathophysiological features of asthma in the lungs: increased numbers of inflammatory cells of the airways, airway hyperresponsiveness, increased vascular permeability, and increased levels of VEGF. Administration of cysLT receptor antagonists markedly reduced plasma extravasation and VEGF levels in allergen-induced asthmatic lungs.


CONCLUSIONS
These results indicate that cysLT receptor antagonists modulate vascular permeability by reducing VEGF expression and suggest that cysLT receptor may regulate the VEGF expression.
Lee
Kyung S
KS
Department of Internal Medicine, Research Center for Allergic Immune Diseases, Chonbuk National University Medical School, 634-18 Keumamdong, Jeonju 561-712, South Korea.
Kim
So R
SR
Park
Hee S
HS
Jin
Gong Y
GY
Lee
Yong C
YC
D000085:Acetates / Q000494:pharmacology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000517:prevention & control; D002199:Capillary Permeability / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D003521:Cyclopropanes; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007211:Indoles / Q000494:pharmacology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000032:analysis; D010047:Ovalbumin / Q000276:immunology; D011804:Quinolines / Q000494:pharmacology; D018077:Receptors, Leukotriene; D040262:Receptors, Vascular Endothelial Growth Factor / Q000502:physiology; D013440:Sulfides; D051996:Transcription Factor RelA; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*
D000085:Acetates; D002867:Chromones; D003521:Cyclopropanes; D016207:Cytokines; D007211:Indoles; D008565:Membrane Proteins; D016328:NF-kappa B; D011804:Quinolines; D018077:Receptors, Leukotriene; C416849:SU 5614; D013440:Sulfides; D051996:Transcription Factor RelA; D042461:Vascular Endothelial Growth Factor A; D010047:Ovalbumin; D040262:Receptors, Vascular Endothelial Growth Factor; C083169:leukotriene D4 receptor; C093875:montelukast; C047681:pranlukast