Pranlukast, a cysteinyl leukotriene receptor 1 antagonist, attenuates allergen-specific tumour necrosis factor alpha production and nuclear factor kappa B nuclear translocation in peripheral blood monocytes from atopic asthmatics.

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Citation

Tomari S, Matsuse H, Machida I, Kondo Y, Kawano T, Obase Y, Fukushima C, Shimoda T, Kohno S

Pranlukast, a cysteinyl leukotriene receptor 1 antagonist, attenuates allergen-specific tumour necrosis factor alpha production and nuclear factor kappa B nuclear translocation in peripheral blood monocytes from atopic asthmatics.

Clin Exp Allergy. 2003 Jun;33(6):795-801.

PubMed ID
12801315 [ View in PubMed
]
Abstract

BACKGROUND: The cysteinyl leukotriene receptor 1 (cysLTR1) antagonists are useful for oral treatment of bronchial asthma. The underlying mechanism of cysLTR1 antagonists on inhibition of inflammatory cytokine production is yet to be determined. OBJECTIVE: The present study was designed to determine the effect of pranlukast, a cysLTR1 antagonist, on production of inflammatory cytokines by allergen-stimulated peripheral blood monocytes (PBM) from atopic asthmatics. METHODS: PBM were obtained from normal control (n = 10) and Dermatophagoides farinae (Der f) allergen-sensitized atopic asthmatics (n = 12), and were cultured in the presence of Der f allergen. The production of TNF-alpha and nuclear-translocation of nuclear factor kappa B (NF-kappa B) was determined. In atopic asthmatics, pranlukast, tacrolimus or dexamethasone was added before stimulation by Der f. The additive effect of pranlukast and dexamethasone was also determined. RESULTS: PBM from atopic asthmatics cultured with Der f exhibited a significant increase in TNF-alpha production and nuclear translocation of NF-kappa B compared with normal control (P < 0.01). Pranlukast, tacrolimus and dexamethasone significantly inhibited production of TNF-alpha and nuclear-translocation of NF-kappa B in PBM of atopic asthmatics (P < 0.01). An additive effect of pranlukast on low-dose dexamethasone was also demonstrated. However, LTD4 did not induce TNF-alpha production or NF-kappa B nuclear translocation. CONCLUSION: Our results suggest that pranlukast may inhibit TNF-alpha production via suppression of NF-kappa B activation through pathways distinct from cysLTR1 antagonism.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
PranlukastNuclear factor NF-kappa-B p105 subunitProteinHumans
Unknown
Other/unknown
Details
PranlukastTumor necrosis factorProteinHumans
Unknown
Other/unknown
Details