title: Cysteinyl leukotrienes induce nuclear factor kappa b activation and RANTES production in a murine model of asthma.
abstract: BACKGROUND
  It has been demonstrated that both cysteinyl leukotrienes (cysLTs) and cytokines are involved in the pathophysiology of bronchial asthma. Nonetheless, the exact mechanism involved in the interaction between these 2 molecules has yet to be determined.
  
  
  OBJECTIVE
  The aim of the present study was to determine the effects of cysLTs on allergic airway inflammation and allergen-specific cytokine production in a murine model of asthma.
  
  
  METHODS
  Four groups of BALB/c mice (control mice, Dermatophagoides farinae allergen-sensitized mice, pranlukast cysLT receptor antagonist-treated allergen-sensitized mice, and dexamethasone-treated allergen-sensitized mice) were examined.
  
  
  RESULTS
  Allergen-sensitized mice exhibited increased airway responsiveness and inflammation. Pranlukast-treated mice showed significant attenuation of these changes concomitant with reduction of T(H)2 cytokine and IFN-gamma production by isolated lung mononuclear cells (MNCs). A much stronger inhibition of all cytokines was noted in dexamethasone-treated mice. Pranlukast also significantly inhibited production of RANTES and activation of nuclear factor kappa B (NF-kappa B) in the isolated lung MNCs. Leukotriene D(4) stimulated isolated lung MNCs to produce RANTES but not any other cytokines and also activated NF-kappa B in these cells.
  
  
  CONCLUSIONS
  Our results suggest that cysLTs activate NF-kappa B and induce RANTES production from isolated lung MNCs, which in turn might cause migration of eosinophils and activated T lymphocytes into the airway.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawano
authors.forename: Hiroto
authors.initials: H
authors.lastname: Matsuse
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kondo
authors.forename: Ikuko
authors.initials: I
authors.lastname: Machida
authors.forename: Sachiko
authors.initials: S
authors.lastname: Saeki
authors.forename: Shinya
authors.initials: S
authors.lastname: Tomari
authors.forename: Kazuko
authors.initials: K
authors.lastname: Mitsuta
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Obase
authors.forename: Chizu
authors.initials: C
authors.lastname: Fukushima
authors.forename: Terufumi
authors.initials: T
authors.lastname: Shimoda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology; D001991:Bronchitis / Q000276:immunology / Q000473:pathology; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D002867:Chromones / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D018836:Inflammation Mediators / Q000494:pharmacology*; D020024:Leukotriene Antagonists / Q000494:pharmacology; D017998:Leukotriene D4 / Q000494:pharmacology; D015289:Leukotrienes / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051996:Transcription Factor RelA
chemical_list: D039741:Antigens, Dermatophagoides; D018946:Chemokine CCL5; D002867:Chromones; D016207:Cytokines; D018836:Inflammation Mediators; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D016328:NF-kappa B; D051996:Transcription Factor RelA; C112381:cysteinyl-leukotriene; D017998:Leukotriene D4; D003545:Cysteine; C047681:pranlukast