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. 1991 Mar;83(3):488–491. doi: 10.1111/j.1365-2249.1991.tb05666.x

Acute-phase protein synthesis in human hepatoma cells: differential regulation of serum amyloid A (SAA) and haptoglobin by interleukin-1 and interleukin-6.

J G Raynes 1, S Eagling 1, K P McAdam 1
PMCID: PMC1535311  PMID: 1706240

Abstract

Interleukin-6 (IL-6, BSF-2 or IFN-beta 2) is thought to be the major regulator of the acute-phase protein response that follows tissue injury and inflammation, with interleukin-1 (IL-1), tumour necrosis factor and more recently, LIF or HSF III, slightly stimulatory on only certain acute phase proteins. The synthesis of the major acute-phase protein SAA, originally described as being synthesized in response to IL-1, has been claimed recently to be mainly under IL-6 regulation. Our results show that in the human hepatoma cell line HuH-7, IL-1 is the major stimulating cytokine increasing SAA synthesis by a factor in excess of 100-fold. We also show that under most conditions interleukin-6 and tumour necrosis factor stimulate additively in combination with IL-1. Isoelectric focusing has demonstrated that SAA1 and SAA2 alpha are expressed but not SAA2 beta. The HuH-7 cell line is IL-6 responsive since haptoglobin is stimulated mainly by IL-6.

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Selected References

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  1. 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]
  2. Baumann H., Wong G. G. Hepatocyte-stimulating factor III shares structural and functional identity with leukemia-inhibitory factor. J Immunol. 1989 Aug 15;143(4):1163–1167. [PubMed] [Google Scholar]
  3. Bausserman L. L., Herbert P. N., Rodger R., Nicolosi R. J. Rapid clearance of serum amyloid A from high-density lipoproteins. Biochim Biophys Acta. 1984 Feb 9;792(2):186–191. doi: 10.1016/0005-2760(84)90221-2. [DOI] [PubMed] [Google Scholar]
  4. Castell J. V., Gómez-Lechón M. J., David M., Andus T., Geiger T., Trullenque R., Fabra R., Heinrich P. C. Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes. FEBS Lett. 1989 Jan 2;242(2):237–239. doi: 10.1016/0014-5793(89)80476-4. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Edbrooke M. R., Burt D. W., Cheshire J. K., Woo P. Identification of cis-acting sequences responsible for phorbol ester induction of human serum amyloid A gene expression via a nuclear factor kappaB-like transcription factor. Mol Cell Biol. 1989 May;9(5):1908–1916. doi: 10.1128/mcb.9.5.1908. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Godenir N. L., Jeenah M. S., Coetzee G. A., Van der Westhuyzen D. R., Strachan A. F., De Beer F. C. Standardisation of the quantitation of serum amyloid A protein (SAA) in human serum. J Immunol Methods. 1985 Nov 7;83(2):217–225. doi: 10.1016/0022-1759(85)90243-1. [DOI] [PubMed] [Google Scholar]
  9. Heinrich P. C., Castell J. V., Andus T. Interleukin-6 and the acute phase response. Biochem J. 1990 Feb 1;265(3):621–636. doi: 10.1042/bj2650621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kushner I., Ganapathi M., Schultz D. The acute phase response is mediated by heterogeneous mechanisms. Ann N Y Acad Sci. 1989;557:19–30. doi: 10.1111/j.1749-6632.1989.tb23996.x. [DOI] [PubMed] [Google Scholar]
  11. Morrone G., Ciliberto G., Oliviero S., Arcone R., Dente L., Content J., Cortese R. Recombinant interleukin 6 regulates the transcriptional activation of a set of human acute phase genes. J Biol Chem. 1988 Sep 5;263(25):12554–12558. [PubMed] [Google Scholar]
  12. Nakabayashi H., Taketa K., Miyano K., Yamane T., Sato J. Growth of human hepatoma cells lines with differentiated functions in chemically defined medium. Cancer Res. 1982 Sep;42(9):3858–3863. [PubMed] [Google Scholar]
  13. Pepys M. B., Baltz M. L. Acute phase proteins with special reference to C-reactive protein and related proteins (pentaxins) and serum amyloid A protein. Adv Immunol. 1983;34:141–212. doi: 10.1016/s0065-2776(08)60379-x. [DOI] [PubMed] [Google Scholar]
  14. Sehgal P. B. Interleukin-6: a regulator of plasma protein gene expression in hepatic and non-hepatic tissues. Mol Biol Med. 1990 Apr;7(2):117–130. [PubMed] [Google Scholar]
  15. Selinger M. J., McAdam K. P., Kaplan M. M., Sipe J. D., Vogel S. N., Rosenstreich D. L. Monokine-induced synthesis of serum amyloid A protein by hepatocytes. Nature. 1980 Jun 12;285(5765):498–500. doi: 10.1038/285498a0. [DOI] [PubMed] [Google Scholar]
  16. Woo P., Sipe J., Dinarello C. A., Colten H. R. Structure of a human serum amyloid A gene and modulation of its expression in transfected L cells. J Biol Chem. 1987 Nov 15;262(32):15790–15795. [PubMed] [Google Scholar]

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