Logo of clinexpimmunolLink to Publisher's site
Clin Exp Immunol. 1991 Mar; 83(3): 488–491.
PMCID: PMC1535311

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


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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (706K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Baumann H, Wong GG. Hepatocyte-stimulating factor III shares structural and functional identity with leukemia-inhibitory factor. J Immunol. 1989 Aug 15;143(4):1163–1167. [PubMed]
  • 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]
  • Bausserman LL, Herbert PN, Rodger R, Nicolosi RJ. Rapid clearance of serum amyloid A from high-density lipoproteins. Biochim Biophys Acta. 1984 Feb 9;792(2):186–191. [PubMed]
  • Castell JV, Gómez-Lechón MJ, David M, Andus T, Geiger T, Trullenque R, Fabra R, Heinrich PC. Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes. FEBS Lett. 1989 Jan 2;242(2):237–239. [PubMed]
  • Castell JV, Gómez-Lechón MJ, David M, Hirano T, Kishimoto T, Heinrich PC. 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. [PubMed]
  • Edbrooke MR, Burt DW, Cheshire JK, 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. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Godenir NL, Jeenah MS, Coetzee GA, Van der Westhuyzen DR, Strachan AF, De Beer FC. Standardisation of the quantitation of serum amyloid A protein (SAA) in human serum. J Immunol Methods. 1985 Nov 7;83(2):217–225. [PubMed]
  • Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem J. 1990 Feb 1;265(3):621–636. [PMC free article] [PubMed]
  • Kushner I, Ganapathi M, Schultz D. The acute phase response is mediated by heterogeneous mechanisms. Ann N Y Acad Sci. 1989;557:19–30. [PubMed]
  • 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]
  • 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]
  • Pepys MB, Baltz ML. 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. [PubMed]
  • Sehgal PB. 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]
  • Selinger MJ, McAdam KP, Kaplan MM, Sipe JD, Vogel SN, Rosenstreich DL. Monokine-induced synthesis of serum amyloid A protein by hepatocytes. Nature. 1980 Jun 12;285(5765):498–500. [PubMed]
  • Woo P, Sipe J, Dinarello CA, Colten HR. 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]

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


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...