Does leukotriene affect intracellular glutathione redox state in cultured human airway epithelial cells?
Leukotrienes (LTs) are one of the most important mediators in the pathophysiology of asthma. We measured the intracellular amounts of reduced glutathione (GSH) and oxidized glutathione (GSSG) in cultured human airway epithelial cells. LTC 4 affects the GSH/GSSG ratio by activating signals to increase interleukin-8 (IL-8) production. Pretreatment with a reducing agent, glutathione monochrome ester (GSH-OEt), and with a leukotriene receptor antagonist, montelukast, significantly suppressed LTC(4)-induced time-dependent changes in the intracellular redox state, and also suppressed upregulation of IL-8 production by suppressing NF-kappaB activation. Our observations led to the hypothesis that LTC(4)-induced oxidative stress is likely to contribute to amplification of airway inflammation.
Wang
Junying
J
Department of Pediatrics and Developmental Medicine, Gunma University Graduate School of Medicine, Gunma, Japan.
Mochizuki
Hiroyuki
H
Todokoro
Makoto
M
Arakawa
Hirokazu
H
Morikawa
Akihiro
A
D000085:Acetates / Q000494:pharmacology; D002478:Cells, Cultured; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000378:metabolism; D006801:Humans; D017997:Leukotriene C4 / Q000494:pharmacology; D015289:Leukotrienes / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013440:Sulfides
D000085:Acetates; D003521:Cyclopropanes; D015289:Leukotrienes; D011804:Quinolines; D013440:Sulfides; D017997:Leukotriene C4; D005978:Glutathione; C093875:montelukast; D019803:Glutathione Disulfide