Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1986 Feb 1;102(2):370–383. doi: 10.1083/jcb.102.2.370

Regulation of major acute-phase plasma proteins by hepatocyte- stimulating factors of human squamous carcinoma cells

PMCID: PMC2114087  PMID: 2418029

Abstract

Human squamous carcinoma (COLO-16) cells release factors which specifically stimulate the synthesis of major acute-phase plasma proteins in human and rodent hepatic cells. Anion exchange, hydroxyapatite, lectin, and gel chromatography of conditioned medium of COLO-16 cells result in separation into three distinct forms of hepatocyte-stimulating factors (designated HSF-I, HSF-II, and HSF-III) with apparent molecular weights of 30,000, 50,000 and 70,000, respectively. None of the preparations contains detectable amounts of thymocyte-stimulating activity. Each of the three HSF forms stimulates the accumulation of mRNA for alpha 1-antichymotrypsin in the human hepatoma cell line, HepG2. When the same factors were added to primary cultures of adult rat hepatocytes, the expression of the same set of plasma proteins was modulated as by nonfractionated medium. The hormonally induced accumulation of mRNA for acute phase proteins is qualitatively comparable to that occurring in the liver of inflamed rats. Unlike in human cells, in rat liver cells dexamethasone acts additively and synergistically with HSFs. The only functional difference between the three HSF forms lies in the level of maximal stimulation. HSF-I represents the predominant form produced by normal human keratinocytes and closely resembles in molecular size and isoelectric point the activity produced by activated peripheral blood monocytes while the larger molecular weight forms are more prevalent in human as well as mouse squamous carcinoma cells. The observation that HSFs from different sources elicit essentially the same pleiotropic response in hepatic cells led to the hypothesis that the species- specific reaction of adult liver cells to inflammatory stimuli is pre- programmed and that the function of any HSF is to trigger and tune the execution of this fixed cellular process.

Full Text

The Full Text of this article is available as a PDF (1.9 MB).

Selected References

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

  1. Barth R. K., Gross K. W., Gremke L. C., Hastie N. D. Developmentally regulated mRNAs in mouse liver. Proc Natl Acad Sci U S A. 1982 Jan;79(2):500–504. doi: 10.1073/pnas.79.2.500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Baumann H., Jahreis G. P., Gaines K. C. Synthesis and regulation of acute phase plasma proteins in primary cultures of mouse hepatocytes. J Cell Biol. 1983 Sep;97(3):866–876. doi: 10.1083/jcb.97.3.866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Buell G. N., Wickens M. P., Payvar F., Schimke R. T. Synthesis of full length cDNAs from four partially purified oviduct mRNAs. J Biol Chem. 1978 Apr 10;253(7):2471–2482. [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Courtoy P. J., Lombart C., Feldmann G., Moguilevsky N., Rogier E. Synchronous increase of four acute phase proteins synthesized by the same hepatocytes during the inflammatory reaction: a combined biochemical and morphologic kinetics study in the rat. Lab Invest. 1981 Feb;44(2):105–115. [PubMed] [Google Scholar]
  8. Crabtree G. R., Kant J. A. Coordinate accumulation of the mRNAs for the alpha, beta, and gamma chains of rat fibrinogen following defibrination. J Biol Chem. 1982 Jul 10;257(13):7277–7279. [PubMed] [Google Scholar]
  9. Crabtree G. R., Kant J. A. Molecular cloning of cDNA for the alpha, beta, and gamma chains of rat fibrinogen. A family of coordinately regulated genes. J Biol Chem. 1981 Sep 25;256(18):9718–9723. [PubMed] [Google Scholar]
  10. Dinarello C. A. Interleukin-1. Rev Infect Dis. 1984 Jan-Feb;6(1):51–95. doi: 10.1093/clinids/6.1.51. [DOI] [PubMed] [Google Scholar]
  11. Enat R., Jefferson D. M., Ruiz-Opazo N., Gatmaitan Z., Leinwand L. A., Reid L. M. Hepatocyte proliferation in vitro: its dependence on the use of serum-free hormonally defined medium and substrata of extracellular matrix. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1411–1415. doi: 10.1073/pnas.81.5.1411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Grunstein M., Hogness D. S. Colony hybridization: a method for the isolation of cloned DNAs that contain a specific gene. Proc Natl Acad Sci U S A. 1975 Oct;72(10):3961–3965. doi: 10.1073/pnas.72.10.3961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jefferson D. M., Clayton D. F., Darnell J. E., Jr, Reid L. M. Posttranscriptional modulation of gene expression in cultured rat hepatocytes. Mol Cell Biol. 1984 Sep;4(9):1929–1934. doi: 10.1128/mcb.4.9.1929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kafatos F. C., Jones C. W., Efstratiadis A. Determination of nucleic acid sequence homologies and relative concentrations by a dot hybridization procedure. Nucleic Acids Res. 1979 Nov 24;7(6):1541–1552. doi: 10.1093/nar/7.6.1541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kampschmidt R. F., Pulliam L. A., Upchurch H. F. Sources of leukocytic endogenous mediator in the rat. Proc Soc Exp Biol Med. 1973 Dec;144(3):882–886. doi: 10.3181/00379727-144-37703. [DOI] [PubMed] [Google Scholar]
  16. Karathanasis S. K., Zannis V. I., Breslow J. L. Isolation and characterization of the human apolipoprotein A-I gene. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6147–6151. doi: 10.1073/pnas.80.20.6147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Knowles B. B., Howe C. C., Aden D. P. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science. 1980 Jul 25;209(4455):497–499. doi: 10.1126/science.6248960. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Kurtz D. T., Nicodemus C. F. Cloning of alpha 2u globulin cDNA using a high efficiency technique for the cloning of trace messenger RNAs. Gene. 1981 Mar;13(2):145–152. doi: 10.1016/0378-1119(81)90003-2. [DOI] [PubMed] [Google Scholar]
  20. Kushner I. The phenomenon of the acute phase response. Ann N Y Acad Sci. 1982;389:39–48. doi: 10.1111/j.1749-6632.1982.tb22124.x. [DOI] [PubMed] [Google Scholar]
  21. Land H., Grez M., Hauser H., Lindenmaier W., Schütz G. 5'-Terminal sequences of eucaryotic mRNA can be cloned with high efficiency. Nucleic Acids Res. 1981 May 25;9(10):2251–2266. doi: 10.1093/nar/9.10.2251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Le P. T., Mortensen R. F. In vitro induction of hepatocyte synthesis of the acute phase reactant mouse serum amyloid P-component by macrophages and IL 1. J Leukoc Biol. 1984 Jun;35(6):587–603. doi: 10.1002/jlb.35.6.587. [DOI] [PubMed] [Google Scholar]
  23. Le P. T., Muller M. T., Mortensen R. F. Acute phase reactants of mice. I. Isolation of serum amyloid P-component (SAP) and its induction by a monokine. J Immunol. 1982 Aug;129(2):665–672. [PubMed] [Google Scholar]
  24. McKnight G. S., Palmiter R. D. Transcriptional regulation of the ovalbumin and conalbumin genes by steroid hormones in chick oviduct. J Biol Chem. 1979 Sep 25;254(18):9050–9058. [PubMed] [Google Scholar]
  25. Okayama H., Berg P. High-efficiency cloning of full-length cDNA. Mol Cell Biol. 1982 Feb;2(2):161–170. doi: 10.1128/mcb.2.2.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ricciardi R. P., Miller J. S., Roberts B. E. Purification and mapping of specific mRNAs by hybridization-selection and cell-free translation. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4927–4931. doi: 10.1073/pnas.76.10.4927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ritchie D. G., Fuller G. M. An in vitro bioassay for leukocytic endogenous mediator(s) using cultured rat hepatocytes. Inflammation. 1981 Dec;5(4):275–287. doi: 10.1007/BF00911093. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Rupp R. G., Fuller G. M. The effects of leucocytic and serum factors on fibrinogen biosynthesis in cultured hepatocytes. Exp Cell Res. 1979 Jan;118(1):23–30. doi: 10.1016/0014-4827(79)90579-2. [DOI] [PubMed] [Google Scholar]
  30. Sanders K. D., Fuller G. M. Kupffer cell regulation of fibrinogen synthesis in hepatocytes. Thromb Res. 1983 Oct 15;32(2):133–145. doi: 10.1016/0049-3848(83)90025-7. [DOI] [PubMed] [Google Scholar]
  31. Sauder D. N., Carter C. S., Katz S. I., Oppenheim J. J. Epidermal cell production of thymocyte activating factor (ETAF). J Invest Dermatol. 1982 Jul;79(1):34–39. doi: 10.1111/1523-1747.ep12510569. [DOI] [PubMed] [Google Scholar]
  32. Seglen P. O. Preparation of isolated rat liver cells. Methods Cell Biol. 1976;13:29–83. doi: 10.1016/s0091-679x(08)61797-5. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. 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]
  35. Sztein M. B., Vogel S. N., Sipe J. D., Murphy P. A., Mizel S. B., Oppenheim J. J., Rosenstreich D. L. The role of macrophages in the acute-phase response: SAA inducer is closely related to lymphocyte activating factor and endogenous pyrogen. Cell Immunol. 1981 Sep 1;63(1):164–176. doi: 10.1016/0008-8749(81)90037-x. [DOI] [PubMed] [Google Scholar]
  36. Ucker D. S., Ross S. R., Yamamoto K. R. Mammary tumor virus DNA contains sequences required for its hormone-regulated transcription. Cell. 1981 Dec;27(2 Pt 1):257–266. doi: 10.1016/0092-8674(81)90409-8. [DOI] [PubMed] [Google Scholar]
  37. Vannice J. L., Taylor J. M., Ringold G. M. Glucocorticoid-mediated induction of alpha 1-acid glycoprotein: evidence for hormone-regulated RNA processing. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4241–4245. doi: 10.1073/pnas.81.14.4241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wannemacher R. W., Jr, Pekarek R. S., Thompson W. L., Curnow R. T., Beall F. A., Zenser T. V., DeRubertis F. R., Beisel W. R. A protein from polymorphonuclear leukocytes (LEM) which affects the rate of hepatic amino acid transport and synthesis of acute-phase globulins. Endocrinology. 1975 Mar;96(3):651–661. doi: 10.1210/endo-96-3-651. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES