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Inflammation

A new target for aspirin

Nature volume 396, pages 15–17 (1998)Cite this article

“Take two aspirin and call me in the morning” seems like a tired cliché. Nevertheless, for many common physical ailments, low doses of aspirin (acetylsalicylic acid) will make you feel better, and high doses of the drug give sustained relief from the symptoms of chronic inflammatory diseases such as rheumatoid arthritis1. Aspirin irreversibly inhibits the cyclooxygenases — enzymes that control the production of prostaglandins (small molecules that induce the pain and fever associated with infection or trauma2). However, the difference in the clinical activities of aspirin at low and high doses has led to speculation that not all the benefits of aspirin derive from inhibition of cyclooxygenases. So what might be the target for high doses of the drug? On page 77 of this issue, Yin et al.3 report that high concentrations of aspirin inhibit the recently discovered enzyme IκB kinase-β (IKK-β), and they propose that this effect partially explains the clinical efficacy of high-dose aspirin.

The IKK enzymes (α and β) catalyse the transfer of phosphate moieties from ATP to IκB (reviewed in ref. 4). Phosphorylation leads to the degradation of IκB and release of NF-κB, a transcription factor that is inhibited by IκB. On release, NF-κB rapidly moves to the nucleus where it binds specific DNA sequences, promoting the transcription of genes that influence defence mechanisms such as inflammatory and immune responses. Thus, if IKK-β is inhibited by aspirin, nuclear localization of NF-κB and subsequent transcription should be blocked. This has, in fact, been observed with high concentrations of aspirin5.

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References

  1. Hart, F. D., Huskisson, E. C. & Ansell, B. M. in Drug Treatment of the Rheumatic Diseases (ed. Hart, F. D.) 7-60 (ADIS, New York, 1982).

  2. Vane, J. R. Nature New Biol. 231, 232–235 (1971).

    Google Scholar 

  3. Yin, M.-J., Yamamoto, Y. & Gaynor, R. B. Nature 396, 77–80 (1998).

    Article  ADS  CAS  Google Scholar 

  4. Israël, A. Nature 388, 519–521 (1997).

    ADS  PubMed  Google Scholar 

  5. Kopp, E. & Ghosh, S. Science 265, 956–958 (1994).

    Google Scholar 

  6. Rainsford, K. D. Aspirin and the Salicylates (Butterworths, Boston, 1984).

  7. Schwenger, P.et al. Proc. Natl Acad. Sci. USA 94, 2869–2873 (1997).

    Google Scholar 

  8. Davis, R. J. Trends Biochem. Sci. 19, 470–473 (1994).

    Google Scholar 

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Authors and Affiliations

  1. Department of Immunology and Rheumatology, Merck Research Laboratories, PO Box 2000, Rahway, 07065-0900, New Jersey, USA

    Edward A. O'Neill

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  1. Edward A. O'Neill
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O'Neill, E. A new target for aspirin. Nature 396, 15–17 (1998). https://doi.org/10.1038/23810

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