Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Bradykinin B1 and B2 receptor agonists synergistically potentiate interleukin-1-induced prostaglandin biosynthesis in human gingival fibroblasts

  • 32 Accesses

  • 65 Citations


The interactions between bradykinin (BK) and interleukin-1 (IL-1) on prostaglandin formation in human gingival fibroblasts have been studied. IL-1α and IL-1β stimulated prostaglandin E2 (PGE2) formation in the gingival fibroblasts with IL-1β being the most potent agonist. The effects of both IL-1α and IL-1β on PGE2 biosynthesis was synergistically potentiated by BK, in a dose-related manner. The synergistic interaction between IL-1β and BK on PGE2 production was seen both with B1 (des-Arg9-BK) and B2 (BK, Lys-BK) BK receptor agonists. No synergistic interaction between BK and IL-1β was seen on arachidonic acid release. These data suggest that BK and IL-1 act in concert to enhance prostanoid formation in inflammatory lesions and that the level of interaction is distal to phospholipase activity.

This is a preview of subscription content, log in to check access.


  1. 1.

    Miller, M. H., andH. S. Margolius. 1989. Kallikrein-kininogen-kinin system.In Endocrinology, 2nd ed., Vol. 3. L. J. DeGroot, G. F. Cahill, Jr., editors. Saunders, Philadelphia, 2491–2503.

  2. 2.

    Proud, D., andA. P. Kaplan. 1988. Kinin formation: mechanisms and role in inflammatory and diabetic diseases.Annu. Rev. Immunol. 6:49–83.

  3. 3.

    Lerner, U. H., K. Sahlbero, andÖ. Ljunggren. 1989. Thrombin and bradykinin enhance prostaglandin production in human peripheral blood monocytes.J. Oral Palhol. Med. 18:246–250.

  4. 4.

    Modéer, T., Ö. Ljunggren, andU. H. Lerner. 1990. Bradykinin-2 receptor-mediated release of [3H]arachidonic acid and formation of prostaglandin E2 in human gingival fibroblasts.J. Periodont. Res. 25:358–363.

  5. 5.

    Lerner, U. H., M. Ransjö, andÖ. Ljunggren. 1989. Bradykinin stimulates production of prostaglandin E2 and prostacyclin in murine osteoblasts.Bone Min. 5:139–154.

  6. 6.

    Ljunggren, Ö., J. Rosenquist, M. Ransjö, andU. H. Lerner 1990. Bradykinin stimulates prostaglandin E2 formation in isolated human osteoblast-like cells.Biosci. Rep. 10:121–126.

  7. 7.

    Lerner, U. H., I. Jones, andG. T. Gustafsson. 1987. Bradykinin, a new potential mediator of inflammatory induced bone resorption. Studies on the effects on mouse calvarial bones and articular cartilage in vitro.Arthritis Rheum. 30:530–540.

  8. 8.

    Dinarello, C. A. 1989. Interleukin-1 and its biologically related cytokines.Adv. Immunol. 44:153–205.

  9. 9.

    Gowen, M., D. D. Wood, E. J. Ihrie, M. K. B. McGuire, andR. G. G. Russell. 1983. An interleukin 1-like factor stimulates bone resorption in vitro.Nature 306:378–380.

  10. 10.

    Raz, A., A. Wyche, N. Siegel, andP. Needleman. 1988. Regulation of fibroblast cyclooxygenase synthesis by interleukin-1.J. Biol. Chem. 263:3022–3028.

  11. 11.

    Modéer, T., G. Dahllöf, andP. Otteskog, 1982. The effect of the phenytoin metabolite p-HPPH on the proliferation of gingival fibroblasts in vitro.Acta Odont. Scand. 40:353–357.

  12. 12.

    Regoli, D., andJ. Barabé. 1980. Pharmacology of bradykinin and related kinins.Pharmacol. Rev. 32:1–46.

  13. 13.

    Whiteley, P. J., andP. Needleman. 1984. Mechanisms of enhanced fibroblast arachidonic acid metabolism by mononuclear cell factor.J. Clin. Invest. 74:2249–2253.

  14. 14.

    Varek, R. J., andJ. M. Stewart. 1985. Competitive antagonists of bradykinin.Peptides 6:161–164.

  15. 15.

    Lerner, U. H. 1991. Bradykinin synergistically potentiates interleukin-1 induced bone resorption and prostanoid biosynthesis in neonatal mouse calvarial bones.Biochem. Biophys. Res. Commun. 175:775–783.

  16. 16.

    Raz, A., A. Wyche, andP. Needleman. 1989. Temporal and pharmacological division of fibroblast cyclooxygenase expression into transcriptional and translational phases.Proc. Natl. Acad. Sci. U.S.A. 86:1657–1661.

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lerner, U.H., Modéer, T. Bradykinin B1 and B2 receptor agonists synergistically potentiate interleukin-1-induced prostaglandin biosynthesis in human gingival fibroblasts. Inflammation 15, 427–436 (1991). https://doi.org/10.1007/BF00923340

Download citation


  • Prostaglandin
  • Arachidonic Acid
  • PGE2
  • Bradykinin
  • Synergistic Interaction