Cysteinyl leukotrienes induce nuclear factor kappa b activation and RANTES production in a murine model of asthma.

Abstract

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. 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. 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. 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. 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.