Cysteinyl leukotriene receptor antagonist MK-571 alters bronchoalveolar lavage fluid proteome in a mouse asthma model.
Cysteinyl leukotriene receptor type 1 (leukotriene CysLT(1) receptor) antagonist is one of the most effective anti-inflammatory agents for asthma. The spectrum of protein targets that can be regulated by leukotriene CysLT(1) receptor antagonist in asthma is not fully understood. The present study tried to identify novel protein targets of a selective leukotriene CysLT(1) receptor antagonist MK-571 in allergic airway inflammation by analyzing the proteome of mouse bronchoalveolar lavage fluid. BALB/c mice sensitized and challenged with ovalbumin showed increased pulmonary inflammatory cell infiltration, airway mucus production and serum ovalbumin-specific IgE level. MK-571 inhibited all these allergic airway inflammation endpoints. Lavage fluid proteins were resolved by two-dimensional gel electrophoresis and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The level of fourteen bronchoalveolar lavage fluid protein spots was markedly altered by MK-571. A family of chitinases (Ym1, Ym2 and acidic mammalian chitinase), lungkine, surfactant protein-D and gamma-actin have been found for the first time to be down-regulated by leukotriene CysLT(1) receptor antagonist in mouse allergic airways. Some of the down-regulatory effects were confirmed with reverse transcription-polymerase chain reaction analyses. Taken together, we have identified novel protein targets that can be regulated by leukotriene CysLT(1) receptor antagonist in mouse allergic airway inflammation, and our findings reveal additional pharmacological actions of leukotriene CysLT(1) receptor antagonist in the treatment of asthma.
Wong
W S Fred
WS
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. phcwongf@nus.edu.sg
Zhu
Hua
H
Liao
Wupeng
W
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000276:immunology; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D020024:Leukotriene Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008853:Microscopy; D011422:Propionates / Q000494:pharmacology / Q000627:therapeutic use*; D020543:Proteome / Q000032:analysis*; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D018077:Receptors, Leukotriene / Q000276:immunology / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000893:Anti-Inflammatory Agents; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D011422:Propionates; D020543:Proteome; D011804:Quinolines; D018077:Receptors, Leukotriene; C059141:verlukast; C083169:leukotriene D4 receptor