Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Nov;90(2):293–299. doi: 10.1111/j.1365-2249.1992.tb07945.x

Production of serum amyloid A and C-reactive protein by HepG2 cells stimulated with combinations of cytokines or monocyte conditioned media: the effects of prednisolone.

J W Smith 1, T L McDonald 1
PMCID: PMC1554599  PMID: 1424289

Abstract

The hepatic production of the acute phase proteins in response to inflammatory cytokines, and the interaction of corticosteroids within this response, has been the subject of considerable recent research. In this study we have examined the effects of the corticosteroid prednisolone on the production of IL-1 alpha and IL-1 beta by lipopolysaccharide (LPS)-stimulated monocytes, and the ability of the monocyte conditioned media (MOCM) obtained under these conditions to induce human hepatoma HepG2 cells to produce serum amyloid A (SAA) and C-reactive protein (CRP). We also examined the production of SAA and CRP by HepG2 cells exposed to different combinations and concentrations of recombinant human (rh) IL-1 alpha, rhIL-1 beta, rhIL-6, recombinant human tumour necrosis factor-alpha (rhTNF-alpha) and prednisolone. The findings indicate: (i) prednisolone substantially inhibits the production of both IL-1 alpha and IL-1 beta by LPS-stimulated monocytes. The MOCM from prednisolone-treated monocytes induced less SAA and CRP production by HepG2 cells; (ii) IL-1 alpha and IL-1 beta both induced CRP and SAA synthesis by HepG2 cells, but only in the presence of IL-6. IL-1 beta was the more potent inducer for SAA production, but for CRP production IL-1 alpha and IL-1 beta were equivalent; (iii) prednisolone enhances the production of SAA by HepG2 cells, but does not enhance the production of CRP; (iv) TNF-alpha in the presence or absence of IL-6 and/or prednisolone did not induce the production of SAA or CRP by HepG2 cells. These findings offer a tenable solution to a disparate production of SAA compared with CRP in corticosteroid-treated cystic fibrosis (CF) patients.

Full text

PDF
293

Selected References

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

  1. Ansel J. C., Luger T. A., Lowry D., Perry P., Roop D. R., Mountz J. D. The expression and modulation of IL-1 alpha in murine keratinocytes. J Immunol. 1988 Apr 1;140(7):2274–2278. [PubMed] [Google Scholar]
  2. 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]
  3. Chambers R. E., Hutton C. W., Dieppe P. A., Whicher J. T. Comparative study of C reactive protein and serum amyloid A protein in experimental inflammation. Ann Rheum Dis. 1991 Oct;50(10):677–679. doi: 10.1136/ard.50.10.677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Endres S., van der Meer J. W., Dinarello C. A. Interleukin-1 in the pathogenesis of fever. Eur J Clin Invest. 1987 Dec;17(6):469–474. doi: 10.1111/j.1365-2362.1987.tb01144.x. [DOI] [PubMed] [Google Scholar]
  5. Ganapathi M. K., May L. T., Schultz D., Brabenec A., Weinstein J., Sehgal P. B., Kushner I. Role of interleukin-6 in regulating synthesis of C-reactive protein and serum amyloid A in human hepatoma cell lines. Biochem Biophys Res Commun. 1988 Nov 30;157(1):271–277. doi: 10.1016/s0006-291x(88)80043-3. [DOI] [PubMed] [Google Scholar]
  6. Ganapathi M. K., Rzewnicki D., Samols D., Jiang S. L., Kushner I. Effect of combinations of cytokines and hormones on synthesis of serum amyloid A and C-reactive protein in Hep 3B cells. J Immunol. 1991 Aug 15;147(4):1261–1265. [PubMed] [Google Scholar]
  7. Ghezzi P., Sipe J. D. Dexamethasone modulation of LPS, IL-1, and TNF stimulated serum amyloid A synthesis in mice. Lymphokine Res. 1988 Summer;7(2):157–166. [PubMed] [Google Scholar]
  8. Ghiara P., Scapigliati G., Censini S., Bartalini M., Bossù P., Armellini D., Nuti S., Volpini G., Dallai R., Boraschi D. IL-1 receptor subtypes possess distinct binding properties for IL-1 alpha and IL-1 beta. Prog Clin Biol Res. 1990;349:271–284. [PubMed] [Google Scholar]
  9. Hogquist K. A., Unanue E. R., Chaplin D. D. Release of IL-1 from mononuclear phagocytes. J Immunol. 1991 Oct 1;147(7):2181–2186. [PubMed] [Google Scholar]
  10. Kenney J. S., Masada M. P., Eugui E. M., Delustro B. M., Mulkins M. A., Allison A. C. Monoclonal antibodies to human recombinant interleukin 1 (IL 1)beta: quantitation of IL 1 beta and inhibition of biological activity. J Immunol. 1987 Jun 15;138(12):4236–4242. [PubMed] [Google Scholar]
  11. Kushner I., Mackiewicz A. Acute phase proteins as disease markers. Dis Markers. 1987 Mar;5(1):1–11. [PubMed] [Google Scholar]
  12. Mackiewicz A., Speroff T., Ganapathi M. K., Kushner I. Effects of cytokine combinations on acute phase protein production in two human hepatoma cell lines. J Immunol. 1991 May 1;146(9):3032–3037. [PubMed] [Google Scholar]
  13. Marhaug G., Permin H., Husby G. Amyloid-related serum protein (SAA) as an indicator of lung infection in cystic fibrosis. Acta Paediatr Scand. 1983 Nov;72(6):861–866. doi: 10.1111/j.1651-2227.1983.tb09831.x. [DOI] [PubMed] [Google Scholar]
  14. Maury C. P., Teppo A. M. Comparative study of serum amyloid-related protein SAA, C-reactive protein, and beta 2-microglobulin as markers of renal allograft rejection. Clin Nephrol. 1984 Dec;22(6):284–292. [PubMed] [Google Scholar]
  15. McDonald T. L., Weber A., Smith J. W. A monoclonal antibody sandwich immunoassay for serum amyloid A (SAA) protein. J Immunol Methods. 1991 Nov 22;144(2):149–155. doi: 10.1016/0022-1759(91)90081-p. [DOI] [PubMed] [Google Scholar]
  16. Mora M., Carinci V., Bensi G., Raugei G., Buonamassa D. T., Melli M. Differential expression of the human IL-1 alpha and beta genes. Prog Clin Biol Res. 1990;349:205–216. [PubMed] [Google Scholar]
  17. Raynes J. G., Eagling S., McAdam K. P. Acute-phase protein synthesis in human hepatoma cells: differential regulation of serum amyloid A (SAA) and haptoglobin by interleukin-1 and interleukin-6. Clin Exp Immunol. 1991 Mar;83(3):488–491. doi: 10.1111/j.1365-2249.1991.tb05666.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sandborg C. I., Berman M. A., Imfeld K. L., Zaldivar F., Jr, Masada M. P., Kenney J. S. Modulation of IL-1 alpha, IL-1 beta, and 25K Mr non-IL-1 activity released by human mononuclear cells. J Leukoc Biol. 1989 Nov;46(5):417–427. doi: 10.1002/jlb.46.5.417. [DOI] [PubMed] [Google Scholar]
  19. Scapigliati G., Ghiara P., Bartalini M., Tagliabue A., Boraschi D. Differential binding of IL-1 alpha and IL-1 beta to receptors on B and T cells. FEBS Lett. 1989 Jan 30;243(2):394–398. doi: 10.1016/0014-5793(89)80169-3. [DOI] [PubMed] [Google Scholar]
  20. Schultz D. R., Arnold P. I. Properties of four acute phase proteins: C-reactive protein, serum amyloid A protein, alpha 1-acid glycoprotein, and fibrinogen. Semin Arthritis Rheum. 1990 Dec;20(3):129–147. doi: 10.1016/0049-0172(90)90055-k. [DOI] [PubMed] [Google Scholar]
  21. Smith J. W., Colombo J. L., McDonald T. L. Comparison of serum amyloid A and C-reactive protein as indicators of lung inflammation in corticosteroid treated and non-corticosteroid treated cystic fibrosis patients. J Clin Lab Anal. 1992;6(4):219–224. doi: 10.1002/jcla.1860060410. [DOI] [PubMed] [Google Scholar]
  22. Smith J. W., McDonald T. L. Use of ethanol-eluted hydrophobic interaction chromatography in the purification of serum amyloid A. Protein Expr Purif. 1991 Apr-Jun;2(2-3):158–161. doi: 10.1016/1046-5928(91)90065-q. [DOI] [PubMed] [Google Scholar]
  23. Stadnyk A. W., Baumann H., Gauldie J. The acute-phase protein response in parasite infection. Nippostrongylus brasiliensis and Trichinella spiralis in the rat. Immunology. 1990 Apr;69(4):588–595. [PMC free article] [PubMed] [Google Scholar]
  24. Tartakovsky B., Kovacs E. J., Takacs L., Durum S. K. T cell clone producing an IL 1-like activity after stimulation by antigen-presenting B cells. J Immunol. 1986 Jul 1;137(1):160–166. [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES