Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Jun;103(2):1327–1332. doi: 10.1111/j.1476-5381.1991.tb09788.x

A novel anti-inflammatory peptide from human lipocortin 5.

M Perretti 1, C Becherucci 1, K G Mugridge 1, E Solito 1, S Silvestri 1, L Parente 1
PMCID: PMC1908345  PMID: 1832064

Abstract

1. A novel anti-inflammatory peptide (residues 204-212) of human recombinant lipocortin 5 (hrLC5) found on the high similarity region with uteroglobin is described. 2. Peptide 204-212 dose-dependently inhibited the contractions of rat isolated stomach strips elicited by porcine pancreatic phospholipase A2 (PLA2). Contractions caused by arachidonic acid (AA), prostaglandin E2 (PGE2) and 5-hydroxytryptamine were not affected. No direct enzyme inhibition was observed in a radiochemical assay. 3. PGE2 release by both human fibroblasts and rat macrophages was reduced by peptide 204-212 in a dose-dependent manner. 4. The development of carrageenin-induced oedema in rats was significantly inhibited by the local administration of peptide 204-212. 5. The pattern and potency of the biological effects of peptide 204-212 are similar to those of antiflammin 2, a lipocortin 1-derived peptide. 6. It is suggested that peptide 204-212 may represent the active site responsible for the anti-inflammatory properties of lipocortin 5.

Full text

PDF
1327

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahn N. G., Teller D. C., Bienkowski M. J., McMullen B. A., Lipkin E. W., de Haën C. Sedimentation equilibrium analysis of five lipocortin-related phospholipase A2 inhibitors from human placenta. Evidence against a mechanistically relevant association between enzyme and inhibitor. J Biol Chem. 1988 Dec 15;263(35):18657–18663. [PubMed] [Google Scholar]
  2. Burch R. M., Axelrod J. Dissociation of bradykinin-induced prostaglandin formation from phosphatidylinositol turnover in Swiss 3T3 fibroblasts: evidence for G protein regulation of phospholipase A2. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6374–6378. doi: 10.1073/pnas.84.18.6374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Camussi G., Tetta C., Bussolino F., Baglioni C. Antiinflammatory peptides (antiflammins) inhibit synthesis of platelet-activating factor, neutrophil aggregation and chemotaxis, and intradermal inflammatory reactions. J Exp Med. 1990 Mar 1;171(3):913–927. doi: 10.1084/jem.171.3.913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Davidson F. F., Dennis E. A., Powell M., Glenney J. R., Jr Inhibition of phospholipase A2 by "lipocortins" and calpactins. An effect of binding to substrate phospholipids. J Biol Chem. 1987 Feb 5;262(4):1698–1705. [PubMed] [Google Scholar]
  6. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Di Rosa M., Giroud J. P., Willoughby D. A. Studies on the mediators of the acute inflammatory response induced in rats in different sites by carrageenan and turpentine. J Pathol. 1971 May;104(1):15–29. doi: 10.1002/path.1711040103. [DOI] [PubMed] [Google Scholar]
  8. Errasfa M., Russo-Marie F. A purified lipocortin shares the anti-inflammatory effect of glucocorticosteroids in vivo in mice. Br J Pharmacol. 1989 Aug;97(4):1051–1058. doi: 10.1111/j.1476-5381.1989.tb12561.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Flower R. J. Eleventh Gaddum memorial lecture. Lipocortin and the mechanism of action of the glucocorticoids. Br J Pharmacol. 1988 Aug;94(4):987–1015. doi: 10.1111/j.1476-5381.1988.tb11614.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Flower R. J., Parente L., Persico P., Salmon J. A. A comparison of the acute inflammatory response in adrenalectomised and sham-operated rats. Br J Pharmacol. 1986 Jan;87(1):57–62. doi: 10.1111/j.1476-5381.1986.tb10156.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Geisow M. J., Fritsche U., Hexham J. M., Dash B., Johnson T. A consensus amino-acid sequence repeat in Torpedo and mammalian Ca2+-dependent membrane-binding proteins. Nature. 1986 Apr 17;320(6063):636–638. doi: 10.1038/320636a0. [DOI] [PubMed] [Google Scholar]
  12. Hayashi H., Owada M. K., Sonobe S., Domae K., Yamanouchi T., Kakunaga T., Kitajima Y., Yaoita H. Monoclonal antibodies specific to a Ca2(+)-bound form of lipocortin I distinguish its Ca2(+)-dependent phospholipid-binding ability from its ability to inhibit phospholipase A2. Biochem J. 1990 Aug 1;269(3):709–715. doi: 10.1042/bj2690709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Huber R., Römisch J., Paques E. P. The crystal and molecular structure of human annexin V, an anticoagulant protein that binds to calcium and membranes. EMBO J. 1990 Dec;9(12):3867–3874. doi: 10.1002/j.1460-2075.1990.tb07605.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ialenti A., Doyle P. M., Hardy G. N., Simpkin D. S., Di Rosa M. Anti-inflammatory effects of vasocortin and nonapeptide fragments of uteroglobin and lipocortin I (antiflammins). Agents Actions. 1990 Jan;29(1-2):48–49. doi: 10.1007/BF01964716. [DOI] [PubMed] [Google Scholar]
  15. Kini R. M., Evans H. J. A model to explain the pharmacological effects of snake venom phospholipases A2. Toxicon. 1989;27(6):613–635. doi: 10.1016/0041-0101(89)90013-5. [DOI] [PubMed] [Google Scholar]
  16. Kretsinger R. H., Creutz C. E. Cell biology. Consensus in exocytosis. Nature. 1986 Apr 17;320(6063):573–573. doi: 10.1038/320573a0. [DOI] [PubMed] [Google Scholar]
  17. Levin S. W., Butler J. D., Schumacher U. K., Wightman P. D., Mukherjee A. B. Uteroglobin inhibits phospholipase A2 activity. Life Sci. 1986 May 19;38(20):1813–1819. doi: 10.1016/0024-3205(86)90135-9. [DOI] [PubMed] [Google Scholar]
  18. Maridonneau-Parini I., Errasfa M., Russo-Marie F. Inhibition of O2- generation by dexamethasone is mimicked by lipocortin I in alveolar macrophages. J Clin Invest. 1989 Jun;83(6):1936–1940. doi: 10.1172/JCI114101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miele L., Cordella-Miele E., Facchiano A., Mukherjee A. B. Novel anti-inflammatory peptides from the region of highest similarity between uteroglobin and lipocortin I. Nature. 1988 Oct 20;335(6192):726–730. doi: 10.1038/335726a0. [DOI] [PubMed] [Google Scholar]
  20. Märki F., Pfeilschifter J., Rink H., Wiesenberg I. 'Antiflammins': two nonapeptide fragments of uteroglobin and lipocortin I have no phospholipase A2-inhibitory and anti-inflammatory activity. FEBS Lett. 1990 May 21;264(2):171–175. doi: 10.1016/0014-5793(90)80241-a. [DOI] [PubMed] [Google Scholar]
  21. Northup J. K., Valentine-Braun K. A., Johnson L. K., Severson D. L., Hollenberg M. D. Evaluation of the antiinflammatory and phospholipase-inhibitory activity of calpactin II/lipocortin I. J Clin Invest. 1988 Oct;82(4):1347–1352. doi: 10.1172/JCI113737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Parente L., Becherucci C., Perretti M., Solito E., Mugridge K. G., Galeotti C. L., Raugei G., Melli M., Sanso M. Are the lipocortins the second messengers of the anti-inflammatory action of glucocorticoids? Prog Clin Biol Res. 1990;349:55–68. [PubMed] [Google Scholar]
  23. Pepinsky R. B., Sinclair L. K., Browning J. L., Mattaliano R. J., Smart J. E., Chow E. P., Falbel T., Ribolini A., Garwin J. L., Wallner B. P. Purification and partial sequence analysis of a 37-kDa protein that inhibits phospholipase A2 activity from rat peritoneal exudates. J Biol Chem. 1986 Mar 25;261(9):4239–4246. [PubMed] [Google Scholar]
  24. 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]
  25. Perretti M., Becherucci C., Scapigliati G., Parente L. The effect of adrenalectomy on interleukin-1 release in vitro and in vivo. Br J Pharmacol. 1989 Dec;98(4):1137–1142. doi: 10.1111/j.1476-5381.1989.tb12657.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Solito E., Parente L. Modulation of phospholipase A2 activity in human fibroblasts. Br J Pharmacol. 1989 Mar;96(3):656–660. doi: 10.1111/j.1476-5381.1989.tb11865.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. VANE J. R. A sensitive method for the assay of 5-hydroxytryptamine. Br J Pharmacol Chemother. 1957 Sep;12(3):344–349. doi: 10.1111/j.1476-5381.1957.tb00146.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wightman P. D., Dahlgren M. E., Davies P., Bonney R. J. The selective release of phospholipase A2 by resident mouse peritoneal macrophages. Biochem J. 1981 Nov 15;200(2):441–444. doi: 10.1042/bj2000441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. van Binsbergen J., Slotboom A. J., Aarsman A. J., de Haas G. H. Synthetic peptide from lipocortin I has no phospholipase A2 inhibitory activity. FEBS Lett. 1989 Apr 24;247(2):293–297. doi: 10.1016/0014-5793(89)81355-9. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES