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Macrophage-Mediated Modulation of Hepatocyte Protein Synthesis: Effect of Dexamethasone

Macrophage-Mediated Modulation of Hepatocyte Protein Synthesis: Effect of Dexamethasone Abstract • We have previously reported an in vitro model demonstrating decreased hepatocyte protein synthesis following co-culture with macrophage-rich peritoneal cells (MRPC) in Sprague-Dawley rats. These observations have been proposed by us and others to represent a possible model for macrophage- or Kupffer cell—mediated modulation of hepatocyte function. Such a mechanism may play a role in the etiology of hepatic failure in sepsis. This effect is shown in this investigation to be completely blocked by dexamethasone at concentrations equal to or greater than 10 −9M. The presence of lymphocyte-activating factor in the MRPC-conditioned medium is suppressed at the same concentration of dexamethasone. Resident MRPC were shown to secrete significant amounts of lymphocyte-activating factor activity without further in vitro activation. These results support the concept that the MRPC mediation of decreased hepatocyte protein synthesis is inflammatory in nature and possibly associated with macrophage activation. (Arch Surg 1986;121:1199-1205) References 1. Keller GA, West MA, Harty JT, et al: Modulation of hepatocyte protein synthesis during co-cultivation with macrophage-rich peritoneal cells in vitro . Arch Surg 1985;120:180-186.Crossref 2. Keller GA, West MA, Harty JT, et al: Modulation of hepatocyte protein synthesis by endotoxin activated Kupffer cells: III. Evidence for the role of a monokine similar to but not identical with interleukin-1 . Ann Surg 1985; 201:436-443.Crossref 3. West MA, Keller GA, Hyland BJ, et al: Hepatocyte function in sepsis: Kupffer cells mediate a biphasic protein synthesis response in hepatocytes after exposure to endotoxin of killed Escherichia coli . Surgery 1985;98: 388-395. 4. West MA, Keller GA, Cerra FB, et al: Mechanism of hepatic insufficiency in septic multiple system organ failure . Surg Forum 1984;35:44-46. 5. North RJ: The concept of the activated macrophage . J Immunol 1978; 121:806-808. 6. Seglen PO: Preparation of isolated rat liver cells , in Prescott DM (ed): Methods in Cell Biology . New York, Academy Press, 1974, pp 29-83. 7. Oppenheim JJ, Shneyour A, Kook AI: Enhancement of DNA synthesis and cAMP content of mouse thymocytes by mediator(s) derived from adherent cells . J Immunol 1976;116:1466-1472. 8. Keller GA, West MA, Cerra FB, et al: Multiple system organ failure: Modulation of hepatocyte protein synthesis by endotoxin-activated Kupffer cells . Ann Surg 1985;201:87-94. 9. Bray MA, Gordon D: Effects of anti-inflammatory drugs on macrophage prostaglandin biosynthesis . Br J Pharmacol 1976;57:4662-4669. 10. Brune K, Kalin H, Rainsford KD, et al: Dexamethasone inhibits the release of prostaglandins and the formation of autophagic vacuoles from stimulated macrophages . Adv Prostaglandin Thromboxane Res Leukotriene 1980;8:1679-1700. 11. Tashjian AH Jr, Voelkel EF, McDonough J, et al: Hydrocortisone inhibits prostaglandin production by mouse fibrosarcoma cells . Nature 1975;258:739-741.Crossref 12. Vasalli JD, Hamilton J: Macrophage plasminogen activator: Modulation of enzyme production by anti-inflammatory steroids, mitotic inhibitors, and cyclic nucleotides . Cell 1976;8:271-281.Crossref 13. Werb Z: Biochemical actions of glucocorticoids on macrophages in culture . J Exp Med 1978;147:1695-1712.Crossref 14. Werb Z: Hormone receptors and hormonal regulation of macrophage physiological functions , in Vanrurth R (ed): Mononuclear Phagocytes . Dordrecht, the Netherlands, Martinus Nijhoff Publishers, 1980, pp 809-828. 15. Werb Z, Foley R, Munck A: Interaction of glucocorticoids with macrophages: Identification of glucocorticoid receptors in monocytes and macrophages . J Exp Med 1978;147:1684-1694.Crossref 16. Werb Z, Foley R, Munck A: Glucocorticoid receptors and glucocorticoid-sensitive secretion of neutral proteinases in a macrophage line . J Immunol 1978;121:115-126. 17. Bondy PK, Bodel P: Mechanism of action of pyrogenic and antipyretic steroids in vitro , in Wolstenholme GEW, Birch J (eds): Pyrogens and Fever . Edinburgh, Churchill Livingston, 1971, pp 101-103. 18. Dillard GM, Bodel P: Studies on steroid fever: II. Pyrogenic and antipyrogenic activity in vitro of some endogenous steroids of man . J Clin Invest 1970;49:2418-2424.Crossref 19. Goldstein IM, Roos D, Weissmann G, et al: Influence of corticosteroids on human polymorphonuclear leukocyte function in vitro . Inflammation 1976;1:305-325.Crossref 20. Levine PH, Hardin JC, Scoon KL, et al: Effect of corticosteroids on the production of superoxide and hydrogen peroxide and the appearance of chemiluminescence by phagocytosing polymorphonuclear leukocytes . Inflammation 1981;5:19-27.Crossref 21. Laishes BA, Williams GM: Conditions affecting primary cell cultures of functional adult rat hepatocytes: II. Dexamethasone-enhanced longevity and maintenance of morphology . In Vitro 1976;12:821-832.Crossref 22. Tanaka K, Sato M, Tomita Y, et al: Biochemical studies of liver functions in primary cultured hepatocytes of adult rats . J Biochem 1978;84: 937-946. 23. Ritchie DG, Fuller GM: An in vitro bioassay for leukocytic endogenous mediator(s) using cultured rat hepatocytes . Inflammation 1981;5: 275-287.Crossref 24. Jennings RJ, Lawson N, Fears R, et al: Stimulation of the activities of phosphatidate phosphohydrolase and tyrosine aminotransferase in rat hepatocytes by glucocorticoids . FEBS Lett 1981;133:119-122.Crossref 25. Ichihara A, Nakamura T, Tanaka K: Use of hepatocytes in primary culture for biochemical studies on liver functions . Mol Cell Biochem 1982; 43:145-160.Crossref 26. Redshaw JC: An effect of dexamethasone on glycogen metabolism in hepatocyte cultures . FEBS Lett 1980;119:165-168.Crossref 27. Dinarello CA: Interleukin-1 . Rev Infect Dis 1984;6:951-955.Crossref 28. West MA, Keller GA, Cerra FB, et al: Killed Escherichia coli stimulate macrophage-mediated alterations in hepatocellular function during in vitro co-culture. Infect Immun, in press. 29. Knighton DR, Hunt TK, Schenenstuhl H, et al: Oxygen tension regulates the expression of angiogenesis factor by macrophages . Science 1983;221:1283-1285.Crossref 30. Osserman EF, Klockars M, Haiper J, et al: Effects of lysozyme on normal and transformed mammalian cells . Nature 1973;243:331-335.Crossref 31. Nathan CR, Brukner LH, Silverstein SC, et al: Extracellular cytolysis by activated macrophages and granulocytes: I. Pharmacologic triggering of effector cells and the release of hydrogen peroxide . J Exp Med 1979;149:84-99.Crossref 32. Rosenwasser LJ, Dinarello CA: Ability of human leukocytic pyrogen to enhance phytohemagglutinin-induced murine thymocyte proliferation . Cell Immunol 1981;63:134-142.Crossref 33. Dinarello CA, Wolff SM: Pathogenesis of fever in man . N Engl J Med 1978;298:607-612.Crossref 34. Baracos V, Rodemann HP, Dinarello CA, et al: Stimulation of muscle protein degradation and prostaglandin E2 release by leukocytic pyrogen (interleukin-1) . N Engl J Med 1983;308:553-558.Crossref 35. Hooper DC, Steer CJ, Dinarello CA, et al: Haptoglobin and albumin synthesis in isolated rat hepatocytes: Response to potential mediators of the acute-phase reaction . Biochim Biophys Acta 1980;653:118-129.Crossref 36. Rupp RG, Fuller GM: The effects of leukocytic and serum factors on fibrinogen biosynthesis in cultured hepatocytes . Exp Cell Res 1979;118: 23-30.Crossref 37. Sztein MB, Vogel SN, Sipe JD, et al: The role of macrophages in the acute-phase response: SAA inducer is closely related to lymphocyte-activating factor and endogenous pyrogen . Cell Immunol 1981;63:164-176.Crossref 38. Merriman CR, Pulliam LA, Kampschmidt RF: Effect of leukocytic endogenous mediator on C-reactive protein in rabbits (38898) . Exp Biol Med 1975;149:782-784.Crossref 39. Sipe JD, Vogel SN, Ryan JL, et al: Detection of a mediator derived from endotoxin-stimulated macrophages that induces the acute-phase serum amyloid A response in mice . J Exp Med 1979;150:597-606.Crossref 40. Loda M, Clowes GHA Jr, Dinarello CA, et al: Induction of accelerated hepatic protein synthesis by a circulating peptide isolated from the plasma of septic patients . Surg Forum 1983;34:148-151. 41. Lillehei RC, Longerbeam JK, Block JH: Physiology and therapy of bacteremic shock: Experimental and clinical observations . Am J Cardiol 1963;12:599-611.Crossref 42. Pitcairn M, Schuler J, Schumer W, et al: Glucocorticoid and antibiotic effect on experimental gram-negative bacteremia shock . Arch Surg 1975; 110:1012-1019.Crossref 43. Schuler JJ, Erve PR, Schumer W: Glucocorticoid effect on carbohydrate metabolism in the endotoxin-shocked monkey . Ann Surg 1976;183: 345-351.Crossref 44. Schumer W: Steroids in the treatment of clinical septic shock . Ann Surg 1976;9:333-341.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

Macrophage-Mediated Modulation of Hepatocyte Protein Synthesis: Effect of Dexamethasone

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Publisher
American Medical Association
Copyright
Copyright © 1986 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.1986.01400100111021
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Abstract

Abstract • We have previously reported an in vitro model demonstrating decreased hepatocyte protein synthesis following co-culture with macrophage-rich peritoneal cells (MRPC) in Sprague-Dawley rats. These observations have been proposed by us and others to represent a possible model for macrophage- or Kupffer cell—mediated modulation of hepatocyte function. Such a mechanism may play a role in the etiology of hepatic failure in sepsis. This effect is shown in this investigation to be completely blocked by dexamethasone at concentrations equal to or greater than 10 −9M. The presence of lymphocyte-activating factor in the MRPC-conditioned medium is suppressed at the same concentration of dexamethasone. Resident MRPC were shown to secrete significant amounts of lymphocyte-activating factor activity without further in vitro activation. These results support the concept that the MRPC mediation of decreased hepatocyte protein synthesis is inflammatory in nature and possibly associated with macrophage activation. (Arch Surg 1986;121:1199-1205) References 1. Keller GA, West MA, Harty JT, et al: Modulation of hepatocyte protein synthesis during co-cultivation with macrophage-rich peritoneal cells in vitro . Arch Surg 1985;120:180-186.Crossref 2. Keller GA, West MA, Harty JT, et al: Modulation of hepatocyte protein synthesis by endotoxin activated Kupffer cells: III. Evidence for the role of a monokine similar to but not identical with interleukin-1 . Ann Surg 1985; 201:436-443.Crossref 3. West MA, Keller GA, Hyland BJ, et al: Hepatocyte function in sepsis: Kupffer cells mediate a biphasic protein synthesis response in hepatocytes after exposure to endotoxin of killed Escherichia coli . Surgery 1985;98: 388-395. 4. West MA, Keller GA, Cerra FB, et al: Mechanism of hepatic insufficiency in septic multiple system organ failure . Surg Forum 1984;35:44-46. 5. North RJ: The concept of the activated macrophage . J Immunol 1978; 121:806-808. 6. Seglen PO: Preparation of isolated rat liver cells , in Prescott DM (ed): Methods in Cell Biology . New York, Academy Press, 1974, pp 29-83. 7. Oppenheim JJ, Shneyour A, Kook AI: Enhancement of DNA synthesis and cAMP content of mouse thymocytes by mediator(s) derived from adherent cells . J Immunol 1976;116:1466-1472. 8. Keller GA, West MA, Cerra FB, et al: Multiple system organ failure: Modulation of hepatocyte protein synthesis by endotoxin-activated Kupffer cells . Ann Surg 1985;201:87-94. 9. Bray MA, Gordon D: Effects of anti-inflammatory drugs on macrophage prostaglandin biosynthesis . Br J Pharmacol 1976;57:4662-4669. 10. Brune K, Kalin H, Rainsford KD, et al: Dexamethasone inhibits the release of prostaglandins and the formation of autophagic vacuoles from stimulated macrophages . Adv Prostaglandin Thromboxane Res Leukotriene 1980;8:1679-1700. 11. Tashjian AH Jr, Voelkel EF, McDonough J, et al: Hydrocortisone inhibits prostaglandin production by mouse fibrosarcoma cells . Nature 1975;258:739-741.Crossref 12. Vasalli JD, Hamilton J: Macrophage plasminogen activator: Modulation of enzyme production by anti-inflammatory steroids, mitotic inhibitors, and cyclic nucleotides . Cell 1976;8:271-281.Crossref 13. Werb Z: Biochemical actions of glucocorticoids on macrophages in culture . J Exp Med 1978;147:1695-1712.Crossref 14. Werb Z: Hormone receptors and hormonal regulation of macrophage physiological functions , in Vanrurth R (ed): Mononuclear Phagocytes . Dordrecht, the Netherlands, Martinus Nijhoff Publishers, 1980, pp 809-828. 15. Werb Z, Foley R, Munck A: Interaction of glucocorticoids with macrophages: Identification of glucocorticoid receptors in monocytes and macrophages . J Exp Med 1978;147:1684-1694.Crossref 16. Werb Z, Foley R, Munck A: Glucocorticoid receptors and glucocorticoid-sensitive secretion of neutral proteinases in a macrophage line . J Immunol 1978;121:115-126. 17. Bondy PK, Bodel P: Mechanism of action of pyrogenic and antipyretic steroids in vitro , in Wolstenholme GEW, Birch J (eds): Pyrogens and Fever . Edinburgh, Churchill Livingston, 1971, pp 101-103. 18. Dillard GM, Bodel P: Studies on steroid fever: II. Pyrogenic and antipyrogenic activity in vitro of some endogenous steroids of man . J Clin Invest 1970;49:2418-2424.Crossref 19. Goldstein IM, Roos D, Weissmann G, et al: Influence of corticosteroids on human polymorphonuclear leukocyte function in vitro . Inflammation 1976;1:305-325.Crossref 20. Levine PH, Hardin JC, Scoon KL, et al: Effect of corticosteroids on the production of superoxide and hydrogen peroxide and the appearance of chemiluminescence by phagocytosing polymorphonuclear leukocytes . Inflammation 1981;5:19-27.Crossref 21. Laishes BA, Williams GM: Conditions affecting primary cell cultures of functional adult rat hepatocytes: II. Dexamethasone-enhanced longevity and maintenance of morphology . In Vitro 1976;12:821-832.Crossref 22. Tanaka K, Sato M, Tomita Y, et al: Biochemical studies of liver functions in primary cultured hepatocytes of adult rats . J Biochem 1978;84: 937-946. 23. Ritchie DG, Fuller GM: An in vitro bioassay for leukocytic endogenous mediator(s) using cultured rat hepatocytes . Inflammation 1981;5: 275-287.Crossref 24. Jennings RJ, Lawson N, Fears R, et al: Stimulation of the activities of phosphatidate phosphohydrolase and tyrosine aminotransferase in rat hepatocytes by glucocorticoids . FEBS Lett 1981;133:119-122.Crossref 25. Ichihara A, Nakamura T, Tanaka K: Use of hepatocytes in primary culture for biochemical studies on liver functions . Mol Cell Biochem 1982; 43:145-160.Crossref 26. Redshaw JC: An effect of dexamethasone on glycogen metabolism in hepatocyte cultures . FEBS Lett 1980;119:165-168.Crossref 27. Dinarello CA: Interleukin-1 . Rev Infect Dis 1984;6:951-955.Crossref 28. West MA, Keller GA, Cerra FB, et al: Killed Escherichia coli stimulate macrophage-mediated alterations in hepatocellular function during in vitro co-culture. Infect Immun, in press. 29. Knighton DR, Hunt TK, Schenenstuhl H, et al: Oxygen tension regulates the expression of angiogenesis factor by macrophages . Science 1983;221:1283-1285.Crossref 30. Osserman EF, Klockars M, Haiper J, et al: Effects of lysozyme on normal and transformed mammalian cells . Nature 1973;243:331-335.Crossref 31. Nathan CR, Brukner LH, Silverstein SC, et al: Extracellular cytolysis by activated macrophages and granulocytes: I. Pharmacologic triggering of effector cells and the release of hydrogen peroxide . J Exp Med 1979;149:84-99.Crossref 32. Rosenwasser LJ, Dinarello CA: Ability of human leukocytic pyrogen to enhance phytohemagglutinin-induced murine thymocyte proliferation . Cell Immunol 1981;63:134-142.Crossref 33. Dinarello CA, Wolff SM: Pathogenesis of fever in man . N Engl J Med 1978;298:607-612.Crossref 34. Baracos V, Rodemann HP, Dinarello CA, et al: Stimulation of muscle protein degradation and prostaglandin E2 release by leukocytic pyrogen (interleukin-1) . N Engl J Med 1983;308:553-558.Crossref 35. Hooper DC, Steer CJ, Dinarello CA, et al: Haptoglobin and albumin synthesis in isolated rat hepatocytes: Response to potential mediators of the acute-phase reaction . Biochim Biophys Acta 1980;653:118-129.Crossref 36. Rupp RG, Fuller GM: The effects of leukocytic and serum factors on fibrinogen biosynthesis in cultured hepatocytes . Exp Cell Res 1979;118: 23-30.Crossref 37. Sztein MB, Vogel SN, Sipe JD, et al: The role of macrophages in the acute-phase response: SAA inducer is closely related to lymphocyte-activating factor and endogenous pyrogen . Cell Immunol 1981;63:164-176.Crossref 38. Merriman CR, Pulliam LA, Kampschmidt RF: Effect of leukocytic endogenous mediator on C-reactive protein in rabbits (38898) . Exp Biol Med 1975;149:782-784.Crossref 39. Sipe JD, Vogel SN, Ryan JL, et al: Detection of a mediator derived from endotoxin-stimulated macrophages that induces the acute-phase serum amyloid A response in mice . J Exp Med 1979;150:597-606.Crossref 40. Loda M, Clowes GHA Jr, Dinarello CA, et al: Induction of accelerated hepatic protein synthesis by a circulating peptide isolated from the plasma of septic patients . Surg Forum 1983;34:148-151. 41. Lillehei RC, Longerbeam JK, Block JH: Physiology and therapy of bacteremic shock: Experimental and clinical observations . Am J Cardiol 1963;12:599-611.Crossref 42. Pitcairn M, Schuler J, Schumer W, et al: Glucocorticoid and antibiotic effect on experimental gram-negative bacteremia shock . Arch Surg 1975; 110:1012-1019.Crossref 43. Schuler JJ, Erve PR, Schumer W: Glucocorticoid effect on carbohydrate metabolism in the endotoxin-shocked monkey . Ann Surg 1976;183: 345-351.Crossref 44. Schumer W: Steroids in the treatment of clinical septic shock . Ann Surg 1976;9:333-341.Crossref

Journal

Archives of SurgeryAmerican Medical Association

Published: Oct 1, 1986

References