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• W2032386882 abstract "The effect of two derivatives of salicylate, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) and 2-acetoxy-4-trifluoromethylbenzoic acid (triflusal), on the activation of NF-κB elicited by tumour necrosis factor-α (TNF-α) on human umbilical vein endothelial cells (HUVEC) was tested. The expression of the mRNA of vascular cell adhesion molecule-1 (VCAM-1) was studied as an example of a gene the expression of which is regulated by NF-κB. To extend these findings to other systems, the induction of nitric oxide synthase in rat adherent peritoneal macrophages was studied. Both HTB and triflusal were more potent than aspirin or salicylate as inhibitors of the nuclear translocation of NF-κB. The calculation of the IC50 values showed ∼amp;2 mM for HTB, 4 mM for aspirin and >4 mM for salicylate. Comparison of the potency of these compounds on VCAM-1 mRNA expression showed complete inhibition by both triflusal and HTB at a concentration of 4 mM whereas aspirin and salicylate produced only 36–43% inhibition at the same concentration. Inhibition of NF-κB activation was also observed in rat peritoneal macrophages stimulated via their receptors for the Fc portion of the antibody molecule with IgG/ovalbumin immune complexes. This was accompanied by a dose-dependent inhibition of nitrite production by the L-arginine pathway via iNOS. IC50 values for this effect were 1.13±0.12 mM (triflusal), 1.84±0.34 (HTB), 6.08±1.53 mM (aspirin) and 9.16±1.9 mM (salicylate). These data indicate that the incorporation of a 4-trifluoromethyl group to the salicylate molecule strongly enhances its inhibitory effect on NF-κB activation, VCAM-1 mRNA expression and iNOS induction, irrespective of the presence of the acetyl moiety involved in the inhibition of cyclo-oxygenase. British Journal of Pharmacology (1999) 126, 1359–1366; doi:10.1038/sj.bjp.0702441" @default.
• W2032386882 created "2016-06-24" @default.
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• W2032386882 date "1999-03-01" @default.
• W2032386882 modified "2023-09-27" @default.
• W2032386882 title "4-trifluoromethyl derivatives of salicylate, triflusal and its main metabolite 2-hydroxy-4-trifluoromethylbenzoic acid, are potent inhibitors of nuclear factor κB activation" @default.
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• W2032386882 doi "https://doi.org/10.1038/sj.bjp.0702441" @default.
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