Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1990 Jan;136(1):39–47.

Regulation of fibronectin synthesis by interleukin-1 and interleukin-6 in rat hepatocytes.

T Hagiwara 1, H Suzuki 1, I Kono 1, H Kashiwagi 1, Y Akiyama 1, K Onozaki 1
PMCID: PMC1877464  PMID: 2404418

Abstract

The authors have observed previously that recombinant human interleukin-1 (rhIL-1) administered into rats increased plasma fibronectin (Fn) level concomitant with the increase of Fn in the liver. Because IL-1 induces interleukin-6 (IL-6) in certain cell types, the IL-1 effect might be mediated by IL-6. To evaluate this possibility, the effect of recombinant human interleukin-6 (rhIL-6), rhIL-1 alpha, and rhIL-1 beta on Fn synthesis in cultured rat hepatocytes was studied. It was shown that rhIL-6 increased Fn synthesis in hepatocytes, in contrast, rhIL-1 alpha, rhIL-I beta and TNF did not have any effect on Fn synthesis. When we studied the interaction of IL-1 and IL-6, IL-1 did not exhibit any synergistic effect with IL-6. Conditioned medium (CM) from rhIL-1 stimulated peripheral blood monocytes (PBM) increased the Fn synthesis, and its activity was neutralized significantly by anti-rhIL-6 antibodies. The CM from rhIL-1-stimulated PBM was analyzed by enzyme linked immunosorbent assay and revealed the increase of IL-6. Furthermore, it was found that intraperitoneal administration of rhIL-1 induced IL-6 into blood. The administration of rhIL-6 into rats increased circulating Fn levels. These results strongly suggest that the in vivo effect of IL-1 on Fn synthesis is mediated by IL-6.

Full text

PDF
39

Images in this article

44Figure 5
on p.44

Selected References

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

  1. Amrani D. L., Mauzy-Melitz D., Mosesson M. W. Effect of hepatocyte-stimulating factor and glucocorticoids on plasma fibronectin levels. Biochem J. 1986 Sep 1;238(2):365–371. doi: 10.1042/bj2380365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andus T., Geiger T., Hirano T., Kishimoto T., Heinrich P. C. Action of recombinant human interleukin 6, interleukin 1 beta and tumor necrosis factor alpha on the mRNA induction of acute-phase proteins. Eur J Immunol. 1988 May;18(5):739–746. doi: 10.1002/eji.1830180513. [DOI] [PubMed] [Google Scholar]
  3. Andus T., Geiger T., Hirano T., Northoff H., Ganter U., Bauer J., Kishimoto T., Heinrich P. C. Recombinant human B cell stimulatory factor 2 (BSF-2/IFN-beta 2) regulates beta-fibrinogen and albumin mRNA levels in Fao-9 cells. FEBS Lett. 1987 Aug 31;221(1):18–22. doi: 10.1016/0014-5793(87)80344-7. [DOI] [PubMed] [Google Scholar]
  4. Auron P. E., Warner S. J., Webb A. C., Cannon J. G., Bernheim H. A., McAdam K. J., Rosenwasser L. J., LoPreste G., Mucci S. F., Dinarello C. A. Studies on the molecular nature of human interleukin 1. J Immunol. 1987 Mar 1;138(5):1447–1456. [PubMed] [Google Scholar]
  5. Baumann H., Firestone G. L., Burgess T. L., Gross K. W., Yamamoto K. R., Held W. A. Dexamethasone regulation of alpha 1-acid glycoprotein and other acute phase reactants in rat liver and hepatoma cells. J Biol Chem. 1983 Jan 10;258(1):563–570. [PubMed] [Google Scholar]
  6. Baumann H., Jahreis G. P., Sauder D. N., Koj A. Human keratinocytes and monocytes release factors which regulate the synthesis of major acute phase plasma proteins in hepatic cells from man, rat, and mouse. J Biol Chem. 1984 Jun 10;259(11):7331–7342. [PubMed] [Google Scholar]
  7. Baumann H., Onorato V., Gauldie J., Jahreis G. P. Distinct sets of acute phase plasma proteins are stimulated by separate human hepatocyte-stimulating factors and monokines in rat hepatoma cells. J Biol Chem. 1987 Jul 15;262(20):9756–9768. [PubMed] [Google Scholar]
  8. Baumann H., Richards C., Gauldie J. Interaction among hepatocyte-stimulating factors, interleukin 1, and glucocorticoids for regulation of acute phase plasma proteins in human hepatoma (HepG2) cells. J Immunol. 1987 Dec 15;139(12):4122–4128. [PubMed] [Google Scholar]
  9. Brodin B., von Schenck H., Schildt B., Liljedahl S. O. Low plasma fibronectin indicates septicaemia in major burns. Acta Chir Scand. 1984;150(1):5–11. [PubMed] [Google Scholar]
  10. Castell J. V., Gómez-Lechón M. J., David M., Hirano T., Kishimoto T., Heinrich P. C. Recombinant human interleukin-6 (IL-6/BSF-2/HSF) regulates the synthesis of acute phase proteins in human hepatocytes. FEBS Lett. 1988 May 23;232(2):347–350. doi: 10.1016/0014-5793(88)80766-x. [DOI] [PubMed] [Google Scholar]
  11. Content J., De Wit L., Poupart P., Opdenakker G., Van Damme J., Billiau A. Induction of a 26-kDa-protein mRNA in human cells treated with an interleukin-1-related, leukocyte-derived factor. Eur J Biochem. 1985 Oct 15;152(2):253–257. doi: 10.1111/j.1432-1033.1985.tb09191.x. [DOI] [PubMed] [Google Scholar]
  12. Darlington G. J., Wilson D. R., Lachman L. B. Monocyte-conditioned medium, interleukin-1, and tumor necrosis factor stimulate the acute phase response in human hepatoma cells in vitro. J Cell Biol. 1986 Sep;103(3):787–793. doi: 10.1083/jcb.103.3.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gauldie J., Richards C., Harnish D., Lansdorp P., Baumann H. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7251–7255. doi: 10.1073/pnas.84.20.7251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gauldie J., Sauder D. N., McAdam K. P., Dinarello C. A. Purified interleukin-1 (IL-1) from human monocytes stimulates acute-phase protein synthesis by rodent hepatocytes in vitro. Immunology. 1987 Feb;60(2):203–207. [PMC free article] [PubMed] [Google Scholar]
  15. Hagiwara T., Kono I., Nemoto K., Kashiwagi H., Onozaki K. Recombinant interleukin-1 triggers the increase of circulating fibronectin level in rats. Int Arch Allergy Appl Immunol. 1989;89(4):376–380. doi: 10.1159/000234978. [DOI] [PubMed] [Google Scholar]
  16. Koj A., Gauldie J., Regoeczi E., Sauder D. N., Sweeney G. D. The acute-phase response of cultured rat hepatocytes. System characterization and the effect of human cytokines. Biochem J. 1984 Dec 1;224(2):505–514. doi: 10.1042/bj2240505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Koj A., Gauldie J., Sweeney G. D., Regoeczi E., Sauder D. N. A simple bioassay for monocyte-derived hepatocyte stimulating factor: increased synthesis of alpha 2-macroglobulin and reduced synthesis of albumin by cultured rat hepatocytes. J Immunol Methods. 1985 Feb 11;76(2):317–327. doi: 10.1016/0022-1759(85)90309-6. [DOI] [PubMed] [Google Scholar]
  18. Matsuda M., Yoshida N., Aoki N., Wakabayashi K. Distribution of cold-insoluble globulin in plasma and tissues. Ann N Y Acad Sci. 1978 Jun 20;312:74–92. doi: 10.1111/j.1749-6632.1978.tb16794.x. [DOI] [PubMed] [Google Scholar]
  19. Matsuda T., Hirano T., Kishimoto T. Establishment of an interleukin 6 (IL 6)/B cell stimulatory factor 2-dependent cell line and preparation of anti-IL 6 monoclonal antibodies. Eur J Immunol. 1988 Jun;18(6):951–956. doi: 10.1002/eji.1830180618. [DOI] [PubMed] [Google Scholar]
  20. May L. T., Ghrayeb J., Santhanam U., Tatter S. B., Sthoeger Z., Helfgott D. C., Chiorazzi N., Grieninger G., Sehgal P. B. Synthesis and secretion of multiple forms of beta 2-interferon/B-cell differentiation factor 2/hepatocyte-stimulating factor by human fibroblasts and monocytes. J Biol Chem. 1988 Jun 5;263(16):7760–7766. [PubMed] [Google Scholar]
  21. Nilsson T. K., Domellöf L., Berghem L. Effects of partial hepatectomy on plasma fibronectin concentrations in the rat. Br J Exp Pathol. 1987 Jun;68(3):421–425. [PMC free article] [PubMed] [Google Scholar]
  22. Owens M. R., Cimino C. D. Synthesis of fibronectin by the isolated perfused rat liver. Blood. 1982 Jun;59(6):1305–1309. [PubMed] [Google Scholar]
  23. Perlmutter D. H., Dinarello C. A., Punsal P. I., Colten H. R. Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression. J Clin Invest. 1986 Nov;78(5):1349–1354. doi: 10.1172/JCI112721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Richards P. S., Saba T. M. Fibronectin levels during intraperitoneal inflammation. Infect Immun. 1983 Mar;39(3):1411–1418. doi: 10.1128/iai.39.3.1411-1418.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Richards W. O., Scovill W. A., Shin B. Opsonic fibronectin deficiency in patients with intra-abdominal infection. Surgery. 1983 Aug;94(2):210–217. [PubMed] [Google Scholar]
  26. Ritchie D. G., Fuller G. M. Hepatocyte-stimulating factor: a monocyte-derived acute-phase regulatory protein. Ann N Y Acad Sci. 1983 Jun 27;408:490–502. doi: 10.1111/j.1749-6632.1983.tb23268.x. [DOI] [PubMed] [Google Scholar]
  27. Rubli E., Büssard S., Frei E., Lundsgaard-Hansen P., Pappova E. Plasma fibronectin and associated variables in surgical intensive care patients. Ann Surg. 1983 Mar;197(3):310–317. doi: 10.1097/00000658-198303000-00011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Saba T. M., Blumenstock F. A., Weber P., Kaplan J. E. Physiologic role of cold-insoluble globulin in systemic host defense: implications of its characterization as the opsonic alpha 2-surface-binding glycoprotein. Ann N Y Acad Sci. 1978 Jun 20;312:43–55. doi: 10.1111/j.1749-6632.1978.tb16792.x. [DOI] [PubMed] [Google Scholar]
  29. Sztein M. B., Luger T. A., Oppenheim J. J. An epidermal cell-derived cytokine triggers the in vivo synthesis of serum amyloid A by hepatocytes. J Immunol. 1982 Jul;129(1):87–90. [PubMed] [Google Scholar]
  30. Takatsuki F., Okano A., Suzuki C., Chieda R., Takahara Y., Hirano T., Kishimoto T., Hamuro J., Akiyama Y. Human recombinant IL-6/B cell stimulatory factor 2 augments murine antigen-specific antibody responses in vitro and in vivo. J Immunol. 1988 Nov 1;141(9):3072–3077. [PubMed] [Google Scholar]
  31. Tamkun J. W., Hynes R. O. Plasma fibronectin is synthesized and secreted by hepatocytes. J Biol Chem. 1983 Apr 10;258(7):4641–4647. [PubMed] [Google Scholar]
  32. Tanaka K., Sato M., Tomita Y., Ichihara A. Biochemical studies on liver functions in primary cultured hepatocytes of adult rats. I. Hormonal effects on cell viability and protein synthesis. J Biochem. 1978 Oct;84(4):937–946. doi: 10.1093/oxfordjournals.jbchem.a132207. [DOI] [PubMed] [Google Scholar]
  33. Tonouchi N., Oouchi N., Kashima N., Kawai M., Nagase K., Okano A., Matsui H., Yamada K., Hirano T., Kishimoto T. High-level expression of human BSF-2/IL-6 cDNA in Escherichia coli using a new type of expression-preparation system. J Biochem. 1988 Jul;104(1):30–34. doi: 10.1093/oxfordjournals.jbchem.a122416. [DOI] [PubMed] [Google Scholar]
  34. Yasukawa K., Hirano T., Watanabe Y., Muratani K., Matsuda T., Nakai S., Kishimoto T. Structure and expression of human B cell stimulatory factor-2 (BSF-2/IL-6) gene. EMBO J. 1987 Oct;6(10):2939–2945. doi: 10.1002/j.1460-2075.1987.tb02598.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES