Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1998 Dec;95(4):507–511. doi: 10.1046/j.1365-2567.1998.00649.x

Bradykinin stimulates interleukin-8 production by human lung fibroblasts.

R Hayashi 1, N Yamashita 1, S Matsui 1, M Maruyama 1, E Sugiyama 1, S Sugiyama 1, M Kobayashi 1
PMCID: PMC1364345  PMID: 9893038

Abstract

Bradykinin (BK) is a potent inflammatory mediator that is generated from kininogens by the actions of plasma and tissue kallikreins. Lung fibroblasts have the potential to participate in the inflammatory responses by releasing proinflammatory cytokines in response to a variety of stimuli. We postulated that human lung fibroblasts might produce interleukin-8 (IL-8) in response to BK stimulation. The present study showed that BK stimulated human lung fibroblasts to produce IL-8 in a dose- and time-dependent manner. Furthermore, Northern blot analysis showed that BK increased IL-8 mRNA expression. The stimulatory effect of BK on IL-8 production was detected at the concentration of 10 nm, and the maximal stimulation was achieved with 100 to 1000 nm. Phorbol 12-myristate 13-acetate pretreatment diminished the ability of BK to stimulate IL-8 production. In addition, GF109203X, a selective protein kinase C inhibitor, blocked BK-induced IL-8 production. These observations suggest that the stimulatory effect of BK on IL-8 production by lung fibroblasts is, at least partially, mediated through protein kinase C. These data suggest that BK may be involved in the inflammatory reaction leading to interstitial lung disorders through stimulating IL-8 production by lung fibroblasts.

Full text

PDF
507

Images in this article

509Figure 3
on p.509
509Figure 4
on p.509

Selected References

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

  1. Baggiolini M., Dewald B., Moser B. Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines. Adv Immunol. 1994;55:97–179. [PubMed] [Google Scholar]
  2. Bhoola K. D., Figueroa C. D., Worthy K. Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev. 1992 Mar;44(1):1–80. [PubMed] [Google Scholar]
  3. Car B. D., Meloni F., Luisetti M., Semenzato G., Gialdroni-Grassi G., Walz A. Elevated IL-8 and MCP-1 in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. Am J Respir Crit Care Med. 1994 Mar;149(3 Pt 1):655–659. doi: 10.1164/ajrccm.149.3.8118632. [DOI] [PubMed] [Google Scholar]
  4. Carré P. C., Mortenson R. L., King T. E., Jr, Noble P. W., Sable C. L., Riches D. W. Increased expression of the interleukin-8 gene by alveolar macrophages in idiopathic pulmonary fibrosis. A potential mechanism for the recruitment and activation of neutrophils in lung fibrosis. J Clin Invest. 1991 Dec;88(6):1802–1810. doi: 10.1172/JCI115501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Christiansen S. C., Proud D., Cochrane C. G. Detection of tissue kallikrein in the bronchoalveolar lavage fluid of asthmatic subjects. J Clin Invest. 1987 Jan;79(1):188–197. doi: 10.1172/JCI112782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cromwell O., Hamid Q., Corrigan C. J., Barkans J., Meng Q., Collins P. D., Kay A. B. Expression and generation of interleukin-8, IL-6 and granulocyte-macrophage colony-stimulating factor by bronchial epithelial cells and enhancement by IL-1 beta and tumour necrosis factor-alpha. Immunology. 1992 Nov;77(3):330–337. [PMC free article] [PubMed] [Google Scholar]
  7. Donnelly S. C., Strieter R. M., Kunkel S. L., Walz A., Robertson C. R., Carter D. C., Grant I. S., Pollok A. J., Haslett C. Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups. Lancet. 1993 Mar 13;341(8846):643–647. doi: 10.1016/0140-6736(93)90416-e. [DOI] [PubMed] [Google Scholar]
  8. Elias J. A., Lentz V., Cummings P. J. Transforming growth factor-beta regulation of IL-6 production by unstimulated and IL-1-stimulated human fibroblasts. J Immunol. 1991 May 15;146(10):3437–3443. [PubMed] [Google Scholar]
  9. Hesselvik J. F., Blombäck M., Brodin B., Maller R. Coagulation, fibrinolysis, and kallikrein systems in sepsis: relation to outcome. Crit Care Med. 1989 Aug;17(8):724–733. doi: 10.1097/00003246-198908000-00002. [DOI] [PubMed] [Google Scholar]
  10. Hong S. L., Levine L. Stimulation of prostaglandin synthesis by bradykinin and thrombin and their mechanisms of action on MC5-5 fibroblasts. J Biol Chem. 1976 Sep 25;251(18):5814–5816. [PubMed] [Google Scholar]
  11. Liebmann C., Graness A., Ludwig B., Adomeit A., Boehmer A., Boehmer F. D., Nürnberg B., Wetzker R. Dual bradykinin B2 receptor signalling in A431 human epidermoid carcinoma cells: activation of protein kinase C is counteracted by a GS-mediated stimulation of the cyclic AMP pathway. Biochem J. 1996 Jan 1;313(Pt 1):109–118. doi: 10.1042/bj3130109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Matsushima K., Morishita K., Yoshimura T., Lavu S., Kobayashi Y., Lew W., Appella E., Kung H. F., Leonard E. J., Oppenheim J. J. Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor. J Exp Med. 1988 Jun 1;167(6):1883–1893. doi: 10.1084/jem.167.6.1883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McIntyre T. M., Zimmerman G. A., Satoh K., Prescott S. M. Cultured endothelial cells synthesize both platelet-activating factor and prostacyclin in response to histamine, bradykinin, and adenosine triphosphate. J Clin Invest. 1985 Jul;76(1):271–280. doi: 10.1172/JCI111957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Miller E. J., Cohen A. B., Nagao S., Griffith D., Maunder R. J., Martin T. R., Weiner-Kronish J. P., Sticherling M., Christophers E., Matthay M. A. Elevated levels of NAP-1/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality. Am Rev Respir Dis. 1992 Aug;146(2):427–432. doi: 10.1164/ajrccm/146.2.427. [DOI] [PubMed] [Google Scholar]
  15. Nakamura H., Yoshimura K., Jaffe H. A., Crystal R. G. Interleukin-8 gene expression in human bronchial epithelial cells. J Biol Chem. 1991 Oct 15;266(29):19611–19617. [PubMed] [Google Scholar]
  16. Paegelow I., Werner H., Vietinghoff G., Wartner U. Release of cytokines from isolated lung strips by bradykinin. Inflamm Res. 1995 Jul;44(7):306–311. doi: 10.1007/BF02032574. [DOI] [PubMed] [Google Scholar]
  17. Pan Z. K., Zuraw B. L., Lung C. C., Prossnitz E. R., Browning D. D., Ye R. D. Bradykinin stimulates NF-kappaB activation and interleukin 1beta gene expression in cultured human fibroblasts. J Clin Invest. 1996 Nov 1;98(9):2042–2049. doi: 10.1172/JCI119009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Proud D., Kaplan A. P. Kinin formation: mechanisms and role in inflammatory disorders. Annu Rev Immunol. 1988;6:49–83. doi: 10.1146/annurev.iy.06.040188.000405. [DOI] [PubMed] [Google Scholar]
  19. Rahman S., Bunning R. A., Dobson P. R., Evans D. B., Chapman K., Jones T. H., Brown B. L., Russell R. G. Bradykinin stimulates the production of prostaglandin E2 and interleukin-6 in human osteoblast-like cells. Biochim Biophys Acta. 1992 Apr 30;1135(1):97–102. doi: 10.1016/0167-4889(92)90172-8. [DOI] [PubMed] [Google Scholar]
  20. Ridings P. C., Blocher C. R., Fisher B. J., Fowler A. A., 3rd, Sugerman H. J. Beneficial effects of a bradykinin antagonist in a model of gram-negative sepsis. J Trauma. 1995 Jul;39(1):81–89. doi: 10.1097/00005373-199507000-00011. [DOI] [PubMed] [Google Scholar]
  21. Rodriguez-Pena A., Rozengurt E. Disappearance of Ca2+-sensitive, phospholipid-dependent protein kinase activity in phorbol ester-treated 3T3 cells. Biochem Biophys Res Commun. 1984 May 16;120(3):1053–1059. doi: 10.1016/s0006-291x(84)80213-2. [DOI] [PubMed] [Google Scholar]
  22. Rolfe M. W., Kunkel S. L., Standiford T. J., Chensue S. W., Allen R. M., Evanoff H. L., Phan S. H., Strieter R. M. Pulmonary fibroblast expression of interleukin-8: a model for alveolar macrophage-derived cytokine networking. Am J Respir Cell Mol Biol. 1991 Nov;5(5):493–501. doi: 10.1165/ajrcmb/5.5.493. [DOI] [PubMed] [Google Scholar]
  23. Roth M., Nauck M., Yousefi S., Tamm M., Blaser K., Perruchoud A. P., Simon H. U. Platelet-activating factor exerts mitogenic activity and stimulates expression of interleukin 6 and interleukin 8 in human lung fibroblasts via binding to its functional receptor. J Exp Med. 1996 Jul 1;184(1):191–201. doi: 10.1084/jem.184.1.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schapira M., Gardaz J. P., Py P., Lew P. D., Perrin L. H., Suter P. M. Prekallikrein activation in the adult respiratory distress syndrome. Bull Eur Physiopathol Respir. 1985 May-Jun;21(3):237–241. [PubMed] [Google Scholar]
  25. Strieter R. M., Kunkel S. L., Showell H. J., Remick D. G., Phan S. H., Ward P. A., Marks R. M. Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-alpha, LPS, and IL-1 beta. Science. 1989 Mar 17;243(4897):1467–1469. doi: 10.1126/science.2648570. [DOI] [PubMed] [Google Scholar]
  26. Strieter R. M., Phan S. H., Showell H. J., Remick D. G., Lynch J. P., Genord M., Raiford C., Eskandari M., Marks R. M., Kunkel S. L. Monokine-induced neutrophil chemotactic factor gene expression in human fibroblasts. J Biol Chem. 1989 Jun 25;264(18):10621–10626. [PubMed] [Google Scholar]
  27. Sugiyama E., Kuroda A., Taki H., Ikemoto M., Hori T., Yamashita N., Maruyama M., Kobayashi M. Interleukin 10 cooperates with interleukin 4 to suppress inflammatory cytokine production by freshly prepared adherent rheumatoid synovial cells. J Rheumatol. 1995 Nov;22(11):2020–2026. [PubMed] [Google Scholar]
  28. Tiffany C. W., Burch R. M. Bradykinin stimulates tumor necrosis factor and interleukin-1 release from macrophages. FEBS Lett. 1989 Apr 24;247(2):189–192. doi: 10.1016/0014-5793(89)81331-6. [DOI] [PubMed] [Google Scholar]
  29. Vandekerckhove F., Opdenakker G., Van Ranst M., Lenaerts J. P., Put W., Billiau A., Van Damme J. Bradykinin induces interleukin-6 and synergizes with interleukin-1. Lymphokine Cytokine Res. 1991 Aug;10(4):285–289. [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES