Pranlukast inhibits NF-kappa B activation in human monocytes/macrophages and T cells.

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Ichiyama T, Hasegawa S, Umeda M, Terai K, Matsubara T, Furukawa S

Pranlukast inhibits NF-kappa B activation in human monocytes/macrophages and T cells.

Clin Exp Allergy. 2003 Jun;33(6):802-7.

PubMed ID

12801316 [ View in PubMed

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Abstract

BACKGROUND: Pranlukast is a leukotriene 1 (LT1) receptor antagonist and is effective against bronchial asthma. Pranlukast inhibits contraction of the tracheal muscle, and thereby antagonizes the binding of LTC4, LTD4 and LTE4. However, the action of pranlukast on monocytes/macrophages and T cells is unknown. OBJECTIVE: We examined whether or not pranlukast inhibits TNF-alpha-induced activation of nuclear transcription factor NF-kappa B, a factor that is essential for the expression of proinflammatory cytokines, on human monocytic 1.3% dimethylsulphoxide (DMSO)-differentiated U-937 cells, which have cysteinyl LT1 (CysLT1) receptors on their membranes, and T cells (Jurkat), which do not. METHODS: We examined whether or not LTC4, LTD4 or LTE4 induced NF-kappa B activation in 1.3% DMSO-differentiated U-937 cells by Western blotting. The inhibitory effects of pranlukast and MK-571, which is an LTD4 receptor-selective antagonist, on TNF-alpha-induced NF-kappa B activation was evaluated by Western blotting and flow cytometry, and those on lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) production in peripheral blood mononuclear cells (PBMC) were evaluated by enzyme-linked immunosorbent assaying. RESULTS: LTC4, LTD4 or LTE4 did not induce NF-kappa B activation in 1.3% DMSO-differentiated U-937 cells. Western blotting demonstrated that 10-5 M pranlukast inhibits NF-kappa B activation in 1.3% DMSO-differentiated U-937 and Jurkat cells by about 40% & 30%, respectively. Flow cytometry demonstrated that pranlukast and MK-571 inhibit NF-kappa B activation in 1.3% DMSO-differentiated U-937 and Jurkat cells in a dose-related manner. Moreover, 10-5 M pranlukast and MK-571 inhibited LPS-induced IL-6 production in PBMC by about 65% and 15%, respectively. CONCLUSION: Pranlukast and MK-571 partially inhibited NF-kappa B activation in 1.3% DMSO-differentiated U-937 and Jurkat cells, and IL-6 release in PBMC. These findings are consistent with the idea that, independently of CysLT1 receptor antagonism, micromolar concentrations of pranlukast suppress the production of proinflammatory cytokines via inhibition of NF-kappa B activation in monocytes/macrophages and T cells, but the contribution of this effect to the anti-inflammatory activity of pranlukast at oral therapeutic doses in asthmatic patients is unclear.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pranlukast	Cysteinyl leukotriene receptor 1	Protein	Humans	Yes	Antagonist	Details
Pranlukast	Nuclear factor NF-kappa-B (Protein Group)	Protein group	Humans	Unknown	Inhibitor	Details
Pranlukast	Nuclear factor NF-kappa-B p105 subunit	Protein	Humans	Unknown	Other/unknown	Details
Pranlukast	Tumor necrosis factor	Protein	Humans	Unknown	Other/unknown	Details