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. 1993 Jan;108(1):62–65. doi: 10.1111/j.1476-5381.1993.tb13440.x

The local anti-inflammatory action of dexamethasone in the rat carrageenin oedema model is reversed by an antiserum to lipocortin 1.

G S Duncan 1, S H Peers 1, F Carey 1, R Forder 1, R J Flower 1
PMCID: PMC1907732  PMID: 8428215

Abstract

1. A local pre-injection of 1 micrograms dexamethasone sodium phosphate strongly inhibited (> 60% inhibition at 3 h; P < 0.001 at all time points) the development of carrageenin-induced paw oedema in the rat induced by a subplantar injection of 0.1 ml, 2% carrageenin. 2. Coinjection of a polyclonal rabbit antiserum raised against human 1-188 recombinant lipocortin 1, which also recognised the rat protein, reversed the inhibitory action of dexamethasone (P < 0.05 at 4 h and 5 h). At the highest volume used (40 microliters) control antisera were without any effect. 3. These data further support the concept that lipocortin 1 is involved in the anti-inflammatory mechanism of action of the glucocorticoids.

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Selected References

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  1. Ambrose M. P., Hunninghake G. W. Corticosteroids increase lipocortin I in alveolar epithelial cells. Am J Respir Cell Mol Biol. 1990 Oct;3(4):349–353. doi: 10.1165/ajrcmb/3.4.349. [DOI] [PubMed] [Google Scholar]
  2. Browning J. L., Ward M. P., Wallner B. P., Pepinsky R. B. Studies on the structural properties of lipocortin-1 and the regulation of its synthesis by steroids. Prog Clin Biol Res. 1990;349:27–45. [PubMed] [Google Scholar]
  3. Carey F., Forder R., Edge M. D., Greene A. R., Horan M. A., Strijbos P. J., Rothwell N. J. Lipocortin 1 fragment modifies pyrogenic actions of cytokines in rats. Am J Physiol. 1990 Aug;259(2 Pt 2):R266–R269. doi: 10.1152/ajpregu.1990.259.2.R266. [DOI] [PubMed] [Google Scholar]
  4. Cirino G., Flower R. J., Browning J. L., Sinclair L. K., Pepinsky R. B. Recombinant human lipocortin 1 inhibits thromboxane release from guinea-pig isolated perfused lung. Nature. 1987 Jul 16;328(6127):270–272. doi: 10.1038/328270a0. [DOI] [PubMed] [Google Scholar]
  5. Cirino G., Flower R. J. Human recombinant lipocortin 1 inhibits prostacyclin production by human umbilical artery in vitro. Prostaglandins. 1987 Jul;34(1):59–62. doi: 10.1016/0090-6980(87)90262-0. [DOI] [PubMed] [Google Scholar]
  6. Cirino G., Peers S. H., Flower R. J., Browning J. L., Pepinsky R. B. Human recombinant lipocortin 1 has acute local anti-inflammatory properties in the rat paw edema test. Proc Natl Acad Sci U S A. 1989 May;86(9):3428–3432. doi: 10.1073/pnas.86.9.3428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Croxtall J. D., Flower R. J. Lipocortin 1 mediates dexamethasone-induced growth arrest of the A549 lung adenocarcinoma cell line. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3571–3575. doi: 10.1073/pnas.89.8.3571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davidson J., Flower R. J., Milton A. S., Peers S. H., Rotondo D. Antipyretic actions of human recombinant lipocortin-1. Br J Pharmacol. 1991 Jan;102(1):7–9. doi: 10.1111/j.1476-5381.1991.tb12122.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Errasfa M., Rothhut B., Fradin A., Billardon C., Junien J. L., Bure J., Russo-Marie F. The presence of lipocortin in human embryonic skin fibroblasts and its regulation by anti-inflammatory steroids. Biochim Biophys Acta. 1985 Nov 20;847(2):247–254. doi: 10.1016/0167-4889(85)90027-8. [DOI] [PubMed] [Google Scholar]
  10. Fuller P. J., Verity K. Somatostatin gene expression in the thymus gland. J Immunol. 1989 Aug 1;143(3):1015–1017. [PubMed] [Google Scholar]
  11. Goulding N. J., Godolphin J. L., Sharland P. R., Peers S. H., Sampson M., Maddison P. J., Flower R. J. Anti-inflammatory lipocortin 1 production by peripheral blood leucocytes in response to hydrocortisone. Lancet. 1990 Jun 16;335(8703):1416–1418. doi: 10.1016/0140-6736(90)91445-g. [DOI] [PubMed] [Google Scholar]
  12. Goulding N. J., Luying P., Guyre P. M. Characteristics of lipocortin 1 binding to the surface of human peripheral blood leucocytes. Biochem Soc Trans. 1990 Dec;18(6):1237–1238. doi: 10.1042/bst0181237. [DOI] [PubMed] [Google Scholar]
  13. Hirata F., Schiffmann E., Venkatasubramanian K., Salomon D., Axelrod J. A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids. Proc Natl Acad Sci U S A. 1980 May;77(5):2533–2536. doi: 10.1073/pnas.77.5.2533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kovacic R. T., Tizard R., Cate R. L., Frey A. Z., Wallner B. P. Correlation of gene and protein structure of rat and human lipocortin I. Biochemistry. 1991 Sep 17;30(37):9015–9021. doi: 10.1021/bi00101a015. [DOI] [PubMed] [Google Scholar]
  15. Pepinsky R. B., Tizard R., Mattaliano R. J., Sinclair L. K., Miller G. T., Browning J. L., Chow E. P., Burne C., Huang K. S., Pratt D. Five distinct calcium and phospholipid binding proteins share homology with lipocortin I. J Biol Chem. 1988 Aug 5;263(22):10799–10811. [PubMed] [Google Scholar]
  16. Piltch A., Sun L., Fava R. A., Hayashi J. Lipocortin-independent effect of dexamethasone on phospholipase activity in a thymic epithelial cell line. Biochem J. 1989 Jul 15;261(2):395–400. doi: 10.1042/bj2610395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Relton J. K., Strijbos P. J., O'Shaughnessy C. T., Carey F., Forder R. A., Tilders F. J., Rothwell N. J. Lipocortin-1 is an endogenous inhibitor of ischemic damage in the rat brain. J Exp Med. 1991 Aug 1;174(2):305–310. doi: 10.1084/jem.174.2.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Saris C. J., Tack B. F., Kristensen T., Glenney J. R., Jr, Hunter T. The cDNA sequence for the protein-tyrosine kinase substrate p36 (calpactin I heavy chain) reveals a multidomain protein with internal repeats. Cell. 1986 Jul 18;46(2):201–212. doi: 10.1016/0092-8674(86)90737-3. [DOI] [PubMed] [Google Scholar]
  19. Solito E., Raugei G., Melli M., Parente L. Dexamethasone induces the expression of the mRNA of lipocortin 1 and 2 and the release of lipocortin 1 and 5 in differentiated, but not undifferentiated U-937 cells. FEBS Lett. 1991 Oct 21;291(2):238–244. doi: 10.1016/0014-5793(91)81293-h. [DOI] [PubMed] [Google Scholar]
  20. Violette S. M., King I., Browning J. L., Pepinsky R. B., Wallner B. P., Sartorelli A. C. Role of lipocortin I in the glucocorticoid induction of the terminal differentiation of a human squamous carcinoma. J Cell Physiol. 1990 Jan;142(1):70–77. doi: 10.1002/jcp.1041420110. [DOI] [PubMed] [Google Scholar]

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