Inhibition of NF-kappaB by sodium salicylate and aspirin.

Kopp E., Ghosh S. Science 1994; 265: 956-9.
(comment by Dany JAFFUEL, Montpellier France)
(partial) translation : | Français/French |  :-)

The salicylates are widely prescribed agents used to treat inflammation. Their effectiveness has been attributed to their ability to inhibit prostaglandin production by inhibiting the cyclooxygenase (COX) synthase. Whereas aspirin inhibits COX synthase by acetaling it, sodium salicylate which lacks an acetyl group and is ineffective as a COX synthase inhibitor, is nevertheless able to reduce inflammation. Because of some the genes involved in the inflammatory response are regulated by NF-kappaB, the authors have examined the effect of salicylates on NF-kappaB activity.

Human Jurkat T cell line and the mouse pre-B cell line (PD 31) were used for experiments. Cells were treated with varying concentrations of sodium salicylate in the presence of the NF-kappaB activator, bacterial lipopolysaccharide (LPS). Using electrophoretic mobility-shift assays with a kappaB site DNA probe, the authors showed that sodium salicylate inhibited the activation of NF-kappaB. Treatment of extracts with deoxycholate (which disrupts the association NF-kappaB with IkappaB and allows the detection of inactive NF-kappaB) indicated that NF-kappaB was present but not active in salicylate-treated cells. Because the phosphorylation and degradation of IkappaBalpha is necessary for the activation of NF-kappaB, the authors examined the amount of IkappaBalpha protein in induced cells that were treated with sodium salicylate. IkappaBalpha concentrations in the sodium salicylate inhibited extracts were the same as in control cells (the amount of IkappaBalpha protein in only LPS treated cells was reduced relative to the control). The authors also examined the effect of sodium salicylate on the expression of reporter gene that is controlled by kappaB site. They used Jurkat T cells transiently transfected with a plasmid containing two kappaB site upstream of a luciferase gene reporter and activated with PMA and PHA in presence or absence of several nonsteroidal anti-inflammatory drugs (sodium salicylate, aspirin, indomethacin). Sodium salicylate and aspirin each effectively inhibited the expression of the reporter gene, indomethacin had no effect.

In this paper, Kopp E. and Ghosh S. showed that sodium salicylate and aspirin inhibited the activation of NF-kappaB by preventing the degradation of IkappaBalpha. Because many of the gene that are abnormally expressed in asthmatic airways are primarily regulated by NF-kappaB, P.J. Barnes had recently suggested: "it may be possible to control asthma by developing specific NF-kappaB blokers" (Mechanism of action of glucocorticoids in asthma. Am J Respir Crit Care Med 1996; 154: S21-S27). Although aspirin is in some cases an important etiologic factor, further clinical trials are needed to determinate if there is a place for aspirin in the treatment of asthma.

Remarques, conseils et suggestions sont les bienvenus; ils seront publiés dans le courrier des lecteurs. Ecrivez/Write to Professeur Philippe Godard ou à la liste de diffusion/Asmanet Forum Asma-L

.AsmanetCongrès Conçue et réalisée par: Michel Godard (at) Top
Date de création: 15 Novembre 1996 - Dernière mise à jour: 28/05/99
Le secret des correspondances transmises sur le réseau Internet n'est pas garanti.
Toute personne citée dispose d'un droit d'accès, de modification, de rectification et de suppression des données le concernant (art. 34 de la loi "Informatique et Libertés" n° 78-17 du 6 janvier 1978). Pour l'éxercer adressez-vous à Michel Godard (at)