Montelukast prevents the decrease of interleukin-10 and inhibits NF-kappaB activation in inflammatory airway of asthmatic guinea pigs.
Interleukin (IL)-10 is an important immunoregulatory and anti-inflammatory cytokine, whereas nuclear factor-kappaB (NF-kappaB) plays an important role in the pathogenesis of asthma. In the present study, the effects of montelukast on the level of IL-10 and on the activation of NF-kappaB in the inflammatory airway of asthmatic guinea pigs were investigated. Guinea pigs were sensitized by ovalbumin. Pulmonary inflammation was observed by hematoxylin and eosin staining. The eosinophils in broncho-alveolar lavage fluid and blood were separated by density gradient centrifugation and counted under microscope. The level of IL-10 in broncho-alveolar lavage fluid was measured by enzyme-linked immunoadsorbent assay. Activation of NF-kappaB in lung tissues was inspected by immunohistochemistry. Montelukast at medium and high doses prevented the decrease of IL-10 in broncho-alveolar lavage fluid (n = 8, p < 0.01 vs. asthma model group), inhibited the activation of NF-kappaB in lung tissues (n = 8; medium dose, p < 0.05; high dose, p < 0.01; vs. asthma model group). There was a significantly negative correlation between the level of IL-10 and the activation of NF-kappaB in lung tissues (r = -0.488, p < 0.01). Montelukast reduced the severity of airway inflammation and the number of eosinophils in asthmatic guinea pigs. From all these findings we conclude that montelukast can prevent the decrease of IL-10 and inhibit the activation of NF-kappaB in inflammatory airway of asthmatic guinea pigs, which may be the new important mechanisms of montelukast's anti-airway-inflammation effects in asthmatic guinea pigs.
Wu
Yuqing
Y
Department of Pharmacology, Nanjing Medical University, 210029, Hanzhong Road 140, Nanjing, China.
Zhou
Chenghua
C
Tao
Jin
J
Li
Shengnan
S
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003521:Cyclopropanes; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D006168:Guinea Pigs; D016753:Interleukin-10 / Q000276:immunology; D007958:Leukocyte Count; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000276:immunology; D011804:Quinolines / Q000494:pharmacology*; D013440:Sulfides
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D016328:NF-kappa B; D011804:Quinolines; D013440:Sulfides; D016753:Interleukin-10; C093875:montelukast