[Zafirlukast inhibition of leukotriene C4 induced endothelin-1 expression in human airway structural cell].
OBJECTIVE
To investigate the effects of a cysteinyl leukotriene receptor antagonist (zafirlukast) on endothelin-1(ET-1) expression in human airway epithelial cell line (16-HBE) and airway smooth muscle cells (ASMC) in response to leukotriene C4(LTC4) stimulation.


METHODS
16-HBE or ASMC was incubated with 10(-8) mol/L LTC4 and graded concentrations of zafirlukast. ET-1 level in supernatant was determined by ELISA and ET-1 mRNA expression was assessed by RT-PCR.


RESULTS
(1) LTC4 induced ET-1 mRNA expression in 16-HBE and ASMC was significantly inhibited by zafirlukast (10(-8) mol/L) 0.23 +/- 0.10 vs. 0.10 +/- 0.03 (16-HBE), t = 3.698, P = 0.034; 0.13 +/- 0.04 vs. 0.04 +/- 0.02 ASMC, t = 4.629, P = 0.019. (2) When graded concentrations of zafirlukast (0, 10(-12) mol/L, 10(-10) mol/L, 10(-8) mol/L, 10(-6) mol/L) were added to the LTC4 cultured 16-HBE and ASMC, a significant inhibition of ET-1 production was observed in both groups cultured with 10(-8) mol/L or more zafirlukast [(12.7 +/- 1.3) ng/L vs (5.5 +/- 2.6) ng/L 16-HBE, t = 4.693, P = 0.019; (7.5 +/- 1.0) ng/L vs (4.4 +/- 0.9) ng/L ASMC (t = 5.003, P = 0.007)]. (3) There was a significant negative linear correlation between ET-1 levels and zafirlukast concentrations in LTC4-treated 16-HBE and ASMC (16-HBE: r = -0.9177, P = 0.0289; ASMC: r = -0.9451, P = 0.0153).


CONCLUSIONS
These data suggest that zafirlukast inhibit LTC4-induced ET-1 over-expression 16-HBE and ASMC, which may be one of the anti-inflammatory mechanism of LTs receptor antagonists.
Chen
A
A
Guangzhou Institute of Respiratory Disease, Guangzhou 510120, China.
Zhong
N
N
D019332:Endothelin-1 / Q000096:biosynthesis* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology; D015870:Gene Expression; D006801:Humans; D007211:Indoles; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D017997:Leukotriene C4 / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D048448:Phenylcarbamates; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012137:Respiratory System / Q000166:cytology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000494:pharmacology*
D019332:Endothelin-1; D007211:Indoles; D020024:Leukotriene Antagonists; D048448:Phenylcarbamates; D012333:RNA, Messenger; D013449:Sulfonamides; D014105:Tosyl Compounds; D017997:Leukotriene C4; C062735:zafirlukast