Diabetologia

, Volume 34, Issue 3, pp 150–156

Heat shock protein induction in rat pancreatic islets by recombinant human interleukin 1β

  • S. Helqvist
  • B. S. Polla
  • J. Johannesen
  • J. Nerup
Originals

Summary

Interleukin 1β, potentiated by tumour necrosis factor α, is cytotoxic to pancreatic Beta cells in vitro. We have hypothesized that interleukin 1β induces oxygen free radicals in Beta cells. Since cytotoxicity induced by free radicals and by heat may activate the same cellular repair mechanism (the heat shock response), the aim of this study was to investigate the pattern of protein synthesis in isolated islets after exposure to interleukin 1β (150 pg/ml, 24 h), tumour necrosis factor α (50 ng/ml, 24 h), heat shock (43°C, 30 min) and H2O2 (0.1 mmol/l, 20 min). By polyacrylamide gel electrophoresis, autoradiography, Western-blot analysis and partial peptide mapping of 35S-methionine labelled islets, interleukin 1β was found to induce a 73 kilodalton protein belonging to the heat shock protein family heat shock protein 70, a heat shock protein 90, and haem oxygenase. A minor induction of heat shock protein 73 and haem oxygenase was seen after H2O2. Interleukin 1β did not induce heat shock proteins in rat thyroid cells, rat mesangial cells or in human monocytes. Tumour necrosis factor α did not induce selective protein synthesis. Pre-exposure of islets to heat, tumour necrosis factor α, or H2O2 did not prevent the impairment of glucose-stimulated insulin release seen after 24 h of interleukin 1β exposure. The data are compatible with free radical induction by interleukin 1β. However, the heat shock response is not specific for oxidative injury, and previous studies have shown discrepant effects as to a protective effect of free radical scavengers against interleukin 1β-mediated beta-cytotoxicity. Thus, a role for free radicals in this context is not definitely proven.

Key words

Interleukin 1β islets of Langerhans heat shock proteins haem oxygenase free radicals Type 1 (insulin-dependent) diabetes mellitus 

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References

  1. 1.
    Bendtzen K, Mandrup-Poulsen T, Nerup J, Nielsen JH, Dinarello CA, Svenson M (1986) Cytotoxicity of human pI 7 Interleukin-1 for pancreatic islets of Langerhans. Science 232: 1545–1547Google Scholar
  2. 2.
    Sandler S, Andersson A, Hellerström C (1987) Inhibitory effects of interleukin-1 on insulin secretion, insulin biosynthesis, and oxidative metabolism of isolated rat pancreatic islets. Endocrinology 121: 1424–1431Google Scholar
  3. 3.
    Mandrup-Poulsen T, Egeberg J, Nerup J, Bendtzen K, Nielsen JH, Dinarello CA (1987) Ultrastructural studies of time course and cellular specificity of interleukin-1 mediated islet cytotoxicity. Acta Path Microbiol Immunol Scand (C) 95: 55–63Google Scholar
  4. 4.
    Sandler S, Bendtzen K, Borg LAH, Eizirik DL, Strandell E, Welsh N (1989) Studies on the mechanisms causing inhibition in rat pancreatic islets exposed to human interleukin-1β indicate a perturbation in the mitochondrial function. Endocrinology 124: 1492–1501Google Scholar
  5. 5.
    Mandrup-Poulsen T, Bendtzen K, Dinarello CA, Nerup J (1987) Human tumor necrosis factor potentiates human interleukin 1-mediated rat pancreatic beta-cell toxicity. J Immunol 139: 4077–4082Google Scholar
  6. 6.
    Eizirik DL (1988) Interleukin 1-induced impairment of pancreatic islet oxidative metabolism of glucose is potentiated by tumor necrosis factor. Acta Endocrinol (Copenh) 119: 321–325Google Scholar
  7. 7.
    Vorbij HAM, Jeucken PHM, Kabel PJ, de Haan M, Drexhage HA (1989) Dendritic cells and scavenger macrophages in pancreatic islets of prediabetic BB rats. Diabetes 38: 1623–1629Google Scholar
  8. 8.
    Nerup J, Mandrup-Poulsen T, Mølvig J, Helqvist S, Wogensen LD, Egeberg J (1988) Mechanisms of pancreatic β-cell destruction in Type I diabetes. Diabetes Care 11 [Suppl 1]: 16–23Google Scholar
  9. 9.
    Kaufmann SHE (1990) Heat shock proteins and the immune response. Immunol Today 11: 129–136Google Scholar
  10. 10.
    Kusher DI, Guding LR (1989) Heat shock alters cell response to tumor necrosis factor. Cytokine 1: 110Google Scholar
  11. 11.
    Polla BS, Healy AM, Wonjo WC, Krane SM (1987) Hormone 1α,25-dihydroxyvitamin D3 modulates heat shock response in monocytes. Am J Physiol 252: C640-C649Google Scholar
  12. 12.
    Wong GWH, Goeddel DV (1988) Induction of manganous superoxide dismutase by tumor necrosis factor: possible protective mechanism. Science 242: 941–944Google Scholar
  13. 13.
    Helqvist S, Hansen BS, Johannesen J, Andersen HU, Nielsen JH, Nerup J (1989) Interleukin 1 induces new protein formation in isolated islets of Langerhans. Acta Endocrinol (Copenh) 121: 136–140Google Scholar
  14. 14.
    Dalbøge H, Bayne S, Christensen T, Hejnæs KR (1989) Cloning and expression of an interleukin-1β precursor and its conversion to interleukin-1β. FEBS Lett 246: 89–93Google Scholar
  15. 15.
    Brunstedt J, Nielsen JH, Lernmark Å and the Hagedorn Study Group (1984) Isolation of islets from mice and rats. In: Larner J, Pohl SL (eds) Methods in diabetes research, vol 1 (Laboratory methods, part C). Wiley & Sons, New York, pp 254–258Google Scholar
  16. 16.
    Heding L (1972) Determination of total serum insulin (IRI) in insulin-treated diabetic patients. Diabetologia 8: 260–266Google Scholar
  17. 17.
    Green IC, Taylor KW (1972) Effects of pregnancy in the rat on the size and the insulin secretory response of the islet of Langerhans. J Endocrinol 54: 317–325Google Scholar
  18. 18.
    Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of the bacteriophage T4. Nature 227: 680–685Google Scholar
  19. 19.
    Welch WJ, Suhan JP (1986) Cellular and biochemical events in mammalian cells during and after recovery from physiological stress. J Cell Biol 103: 2035–2052Google Scholar
  20. 20.
    Keyse SM, Tyrell RM (1987) Both near ultraviolet radiation and the oxidizing agent hydrogen peroxide induce a 32-kDa stress protein in normal human skin fibroblasts. J Biol Chem 262: 14821–14825Google Scholar
  21. 21.
    Keyse SM, Tyrrell RM (1989) Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. Proc Natl Acad Sci USA 86: 99–103Google Scholar
  22. 22.
    Shibahara S, Müller RM, Taguchi H (1987) Transcriptional control of rat heme oxygenase by heat shock. J Biol Chem 262: 12889–12892Google Scholar
  23. 23.
    Donati YRA, Slosman DO, Polla BS (1990) Oxidative injury and the heat shock response. Biochem Pharmacol 40: 2571–2577Google Scholar
  24. 24.
    Kaur P, Welch WJ, Saklatvala J (1989) Interleukin 1 and tumour necrosis factor increase phosphorylation of the small heat shock protein. FEBS Lett 258: 269–273Google Scholar
  25. 25.
    Freeman BA, Crapo JD (1982) Biology of disease. Free radicals and tissue injury. Lab Invest 47: 412–426Google Scholar
  26. 26.
    Helqvist S, Bouchelouche PN, Johannesen J, Nerup J (1990) Interleukin 1β increases the cytosolic free sodium concentration in isolated rat islets of Langerhans. Scand J Immunol 32: 53–58Google Scholar
  27. 27.
    Simchowitz L (1985) Intracellular pH modulates the generation of superoxide radicals by human neutrophils. J Clin Invest 76: 1079–1089Google Scholar
  28. 28.
    Eizirik DL, Sandler S (1989) Human interleukin-1β induced stimulation of insulin release from rat pancreatic islets is accompanied by an increase in mitochondrial oxidative events. Diabetologia 32: 769–773Google Scholar
  29. 29.
    Touati D (1988) Molecular genetics of superoxide dismutases. Free Radical Biol Med 5: 393–402Google Scholar
  30. 30.
    Hassan HM (1988) Biosynthesis and regulation of superoxide dismutases. Free Radical Biol Med 5: 377–385Google Scholar
  31. 31.
    Asayama K, Kooy NW, Burr IM (1986) Effect of vitamin E deficiency on insulin secretory reserve and free radical scavenging systems in islets. J Lab Clin Med 107: 459–464Google Scholar
  32. 32.
    Malaisse WJ, Malaisse-Lagae F, Sener A, Pipeleers DG (1982) Determinants of the selective toxicity of alloxan to the pancreatic B cell. Proc Natl Acad Sci USA 79: 927–930Google Scholar
  33. 33.
    Sumoski W, Baquerizo H, Rabinovitch A (1989) Oxygen free radical scavengers protect rat islet cells from damage by cytokines. Diabetologia 32: 792–796Google Scholar
  34. 34.
    Hammonds P, Beggs M, Beresford G, Espinal J, Clarke J, Mertz RJ (1990) Insulin-secreting β-cells possess specific receptors for interleukin-1β. FEBS Lett 261: 97–100Google Scholar
  35. 35.
    Buscema M, Vinci C, Rabuazzo M, Forte F, Caltabiano V, Squatrito S, Purello F (1990) Nicotinamide improves insulin secretion in islets unresponsive after chronic exposure to IL-1β. Diabetologia 33 [Suppl]: A18 (abstract)Google Scholar
  36. 36.
    Sargent CA, Dunham I, Trowsdale J, Campbell RD (1989) Human major histocompatibility complex contains genes for the major heat shock protein HSP70. Proc Natl Acad Sci USA 86: 1968–1972Google Scholar
  37. 37.
    Wurst W, Benesch C, Drabent B, Rothermel E, Benecke B, Günther E (1989) Localization of heat shock protein 70 genes inside the rat major histocompatibility complex close to class III genes. Immunogenetics 30: 46–49Google Scholar
  38. 38.
    Thomsen M, Mølvig J, Zerbib A et al. (1988) The susceptibility to insulin-dependent diabetes mellitus is associated with C4 allotypes independently of the association with HLA-DQ alleles in HLA-DR3,4 heterozygotes. Immunogenetics 28: 320–327Google Scholar
  39. 39.
    Pociot F, Mølvig J, Wogensen L, Milner C, Campbell Nerup J (1990) Insulin-dependent diabetes — a polygenic disease? Implications of tumor necrosis factor β and heat shock protein 73 polymorphisms. Diabetologia 33 [Suppl]: A83 (abstract)Google Scholar
  40. 40.
    Todd JA, Bell JI, McDevitt HO (1987) 156-01 gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature 329: 599–604Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • S. Helqvist
    • 1
  • B. S. Polla
    • 2
  • J. Johannesen
    • 1
  • J. Nerup
    • 1
  1. 1.Steno Memorial Hospital and Hagedorn Research LaboratoryGentofteDenmark
  2. 2.Allergy UnitUniversity HospitalGenevaSwitzerland

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