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Renocortin: a phospholipase A2 inhibitory protein induced by anti-inflammatory steroids: pharmacological and biological properties, development of monoclonal antibodies

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Abstract

In 1979, we first reported that in order to inhibit prostaglandin (PG) synthesis, anti-inflammatory steroids required glucocorticoid receptor occupancy, ribonucleic acid (RNA) and new protein synthesis (Russo-Marie et al., 1979). As it had been previously demonstrated that steroids were inhibiting PG synthesis by inhibiting the release of arachidonic acid from their membrane phospholipid stores, probably by inhibiting the enzyme responsible for the phospholipid deacylation (Gryglewski et al., 1975; Hong & Levine, 1976), we advanced the hypothesis that this induced protein was able to inhibit phospholipase A2. In the meantime, Flower & Black-well (1979) reported also that anti-inflammatory steroids induced the biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation. In the model they used, they were able to demonstrate that the protein was not only induced but was also released by the cell which had been synthesizing it.

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References

  • BLACKWELL, G.J., CARNUCCIO, R., DI ROSA, M., FLOWER, R.J., LANGHAM, C.S.J., PARENTE, L., PERSICO, P., RUSSEL-SMITH, N.C. & STONE, D. (1982). Glucocorticoids induce the formation and the release of anti-inflammatory and anti-phospholipase proteins into the peritoneal cavity of the rat. Br. J. Pharmac, 76, 185–194.

    Article  Google Scholar 

  • BLACKWELL, G.J., CARNUCCIO, R., DI ROSA, M., FLOWER, R.J., PARENTE, L. & PERSICO, P. (1980). Macrocortin: a polypeptide causing the anti-phospholipase effect of glucocorticoids. Nature, 287, 147–149.

    Article  Google Scholar 

  • CLOIX, J.F., COLARD, O., ROTHHUT, B. & RUSSO-MARIE, F. (1983). Characterization and partial purification of ‘renocortins’: two polypeptides formed in renal cells causing the anti-phospholipase-like action of glucocorticoids. Br. J. Pharmac, 79, 313–321.

    Article  Google Scholar 

  • FLOWER, R.J. & BLACKWELL, G.J. (1979). Antiinflammatory steroids induce biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation. Nature, 275, 456–458.

    Article  Google Scholar 

  • GRYGLEWSKI, R.J., PANCZENKO, B., KORBUT, R., GROD-ZINSKA, L. & OCETKIEWICZ, A. (1975). Corticosteroids inhibit prostaglandin release from perfused mesenteric blood vessels of rabbit and from perfused lungs of sensitized guinea pigs. Prostaglandins, 10, 343–355.

    Article  Google Scholar 

  • HIRATA, F. & IWATA, M. (1983). Role of lipomodulin, phospholipase inhibitory protein in immunoregulation by thymocytes. J. Immunol., 130, 1903–1909.

    Google Scholar 

  • HIRATA, F., NOTSU, Y., IWATA, M., PARENTE, L., DI ROSA, M. & FLOWER, R.J. (1982). Identification of several species of phospholipase inhibitory protein(s), by radioimmunoassay for lipomodulin. Biochem. biophys. Res. Commun., 109, 223–230.

    Article  Google Scholar 

  • HIRATA, F., SCHIFFMANN, E., VENKATASUBRAMANIAN, K., SALOMON, D. & AXELROD, J. (1980). A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticosteroids. Proc. natn. Acad. Sci. U.S.A., 77, 2533–2536.

    Article  Google Scholar 

  • HONG, S.C.L. & LEVINE, L. (1976). Inhibition of arachidonic acid release from cells as the biochemical action of anti-inflammatory corticosteroids. Proc. natn. Acad. Sci. U.S.A., 73, 1730–1734.

    Article  Google Scholar 

  • PARENTE, L., DI ROSA, M., FLOWER, R.J., GHIARA, P., MELI, R., PERSICO, P., SALMON, J.A., & WOOD, J.N. (1984). Relationship between the anti-phospholipase and anti-inflammatory effects of glucocorticoid-induced proteins. Eur. J. Pharmac, 99, 233–241.

    Article  Google Scholar 

  • ROTHHUT, B., RUSSO-MARIE, F., WOOD, J., DI ROSA, M. & FLOWER, R.J. (1983). Further characterization of the glucocorticoid-induced antiphospholipase protein ‘renocortin’. Biochem. biophys. Res. Commun., 117 878–884.

    Article  Google Scholar 

  • RUSSO-MARIE, F. & DUVAL, D. (1982). Dexamethasone-induced inhibition of prostaglandin production appears mediated through a steroid-inducible factor rather than by a direct action on phospholipase activities. Biochim. biophys. Acta, 254, 177–185.

    Article  Google Scholar 

  • RUSSO-MARIE, F., PAING, M. & DUVAL, D. (1979). Involvement of glucocorticoid receptors in steroid induced inhibition of prostaglandin secretion. J. biol. Chem., 254, 8498–8504.

    Google Scholar 

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William Paton James Mitchell Paul Turner

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© 1984 Macmillan Publishers Limited

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Rothhut, B., Russo-Marie, F., Cousin, M., Lando, D. (1984). Renocortin: a phospholipase A2 inhibitory protein induced by anti-inflammatory steroids: pharmacological and biological properties, development of monoclonal antibodies. In: Paton, W., Mitchell, J., Turner, P. (eds) IUPHAR 9th International Congress of Pharmacology. Palgrave, London. https://doi.org/10.1007/978-1-349-86029-6_7

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