Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Cloning and expression of human lipocortin, a phospholipase A2 inhibitor with potential anti-inflammatory activity

Nature volume 320, pages 77–81 (1986)Cite this article

Abstract

The anti-inflammatory action of glucocorticoids has been attributed to the induction of a group of phospholipase A2 inhibitory proteins, collectively called lipocortin. These proteins are thought to control the biosynthesis of the potent mediators of inflammation, prostaglandins and leukotrienes, by inhibiting the release of their common precursor, arachidonic acid, a process that requires phospholipase A2 hydrolysis of phospholipids1–11. Lipocortin-like proteins have been isolated from various cell types, including monocytes3, neutrophils4 and renal medullary9 cell preparations. The predominant active form is a protein with an apparent relative molecular mass (Mr) of 40,000 (40K). These partially purified preparations of lipocortin mimic the effect of steroids, and mediate anti-inflammatory activity in various in vivo model systems3,5,11. Using amino-acid sequence information obtained from purified rat lipocortin, we have now cloned human lipocortin complementary DNA and expressed the gene in Escherichia coli. Our studies confirm that lipocortin is a potent inhibitor of phospholipase A2 activity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Blackwell, G. J. et al. Nature 287, 147–149 (1980).

    Article  ADS  CAS  Google Scholar 

  2. Carnuccio, R., DiRosa, M. & Persico, P., Br. J. Pharmac. 68, 14–16 (1980).

    Article  CAS  Google Scholar 

  3. Flower, R. J. & Blackwell, G. J. Nature 278, 456–459 (1979).

    Article  ADS  CAS  Google Scholar 

  4. Hirata, F. et al. Proc. natn. Acad. ScL U.S.A. 77, 2533–2536 (1980).

    Article  ADS  CAS  Google Scholar 

  5. Cloix, J. F. et al. Br. J. Pharmac. 79, 313–321 (1983).

    Article  CAS  Google Scholar 

  6. Hong, S.-C. & Levine, L. Proc. natn. Acad. Sci. U.S.A. 73, 1720–1734 (1976).

    Article  ADS  Google Scholar 

  7. Blackwell, G. J. et al. Br. J. Pharmac. 62, 79–89 (1978).

    Article  CAS  Google Scholar 

  8. Carnuccio, R. et al. Br. J. Pharmac. 74, 322–324 (1981).

    Article  CAS  Google Scholar 

  9. DiRosa, M. & Persico, P. Br. J. Pharmac. 66, 161–163 (1979).

    Article  CAS  Google Scholar 

  10. Rothhut, B. et al. Biochem. biophys. Res. Commun. 117, 878–884 (1983).

    Article  CAS  Google Scholar 

  11. Flower, R. J., Wood, J. N. & Parente, L. Advances in Inflammation Research Vol. 7 (eds Otterness, I, Capetola, R. & Wong, S.) 61–70 (Raven, New York, 1984).

    Google Scholar 

  12. Pepinsky, R. B. et al. J. biol. Chem. (in the press).

  13. Hirata, F. J. biol. Chem. 256, 7730–7733 (1981).

    CAS  Google Scholar 

  14. Hirata, F. et al. Proc. natn. Acad. Sci. U.S.A. 81, 4717–4721 (1984).

    Article  ADS  CAS  Google Scholar 

  15. Amann, E. & Brosius, J. Gene. 40, 183–190 (1985).

    Article  CAS  Google Scholar 

  16. Matteucci, M. D. & Caruttiers, M. H. J. Am. chem. Soc. 103, 3185–3191 (1981).

    Article  CAS  Google Scholar 

  17. Chirgwin, J. M. et al. Biochemistry 18, 5294–5299 (1979).

    Article  CAS  Google Scholar 

  18. Maniatis, T., Fritsch, E. F. & Sambrook, J. Molecular Cloning, 229–246 (Cold Spring Harbor Laboratory, New York, 1982).

    Google Scholar 

  19. Church, G. M. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 81, 1991–1995 (1984).

    Article  ADS  CAS  Google Scholar 

  20. Huynh, T., Young, R. A. & Davis, R. W. DNA Cloning Techniques, A Practical Approach. (ed. Gloves, D. M.) 49–78 (IRL Press, Oxford, 1985).

    Google Scholar 

  21. Woo, S. L. Meth. Enzym. 68, 389–395 (1979).

    Article  CAS  Google Scholar 

  22. Maxam, A. M. & Gilbert, W. Meth. Enzym. 65, 497–560 (1980).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biogen Research Corp., 14 Cambridge Center, Cambridge, Massachusetts, 02142, USA

    Barbara P. Wallner, Robert J. Mattaliano, Catherine Hession, Richard L. Cate, Richard Tizard, Lesley K. Sinclair, Carl Foeller, E. Pingchang Chow, Jeffrey L. Browning, K. L. Ramachandran & R. Blake Pepinsky

Authors
  1. Barbara P. Wallner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert J. Mattaliano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Catherine Hession
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Richard L. Cate
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard Tizard
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lesley K. Sinclair
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Carl Foeller
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E. Pingchang Chow
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jeffrey L. Browning
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. K. L. Ramachandran
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. R. Blake Pepinsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wallner, B., Mattaliano, R., Hession, C. et al. Cloning and expression of human lipocortin, a phospholipase A2 inhibitor with potential anti-inflammatory activity. Nature 320, 77–81 (1986). https://doi.org/10.1038/320077a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/320077a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing