Cysteinyl leukotrienes induce nuclear factor kappa b activation and RANTES production in a murine model of asthma.
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.
Kawano
Tetsuya
T
Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Matsuse
Hiroto
H
Kondo
Yuki
Y
Machida
Ikuko
I
Saeki
Sachiko
S
Tomari
Shinya
S
Mitsuta
Kazuko
K
Obase
Yasushi
Y
Fukushima
Chizu
C
Shimoda
Terufumi
T
Kohno
Shigeru
S
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
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