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Preserved coupling of oxidative phosphorylation but decreased mitochondrial respiratory capacity in IL-1β-treated human peritoneal mesothelial cells

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Abstract

The peritoneal mesothelium acts as a regulator of serosal responses to injury, infection, and neoplastic diseases. After inflammation of the serosal surfaces, proinflammatory cytokines induce an “activated” mesothelial cell phenotype, the mitochondrial aspect of which has not previously been studied. After incubation of cultured human peritoneal mesothelial cells with interleukin (IL)-1β for 48 h, respiratory activity of suspended cells was analyzed by high-resolution respirometry. Citrate synthase (CS) and lactate dehydrogenase (LDH) activities were determined by spectrophotometry. Treatment with IL-1β resulted in a significant decline of respiratory capacity (p<0.05). Respiratory control ratios (i.e., uncoupled respiration at optimum carbonyl cyanide p-trifluoromethoxyphenylhydrazone concentration divided by oligomycin inhibited respiration measured in unpermeabilized cells) remained as high as 11, indicating well-coupled mitochondria and functional integrity of the inner mitochondrial membrane. Whereas respiratory capacities of the cells declined in proportion with decreased CS activity (p<0.05), LDH activity increased (p<0.05). Taken together, these results indicate that IL-1β exposure of peritoneal mesothelial cells does not lead to irreversible defects or inhibition of specific components of the respiratory chain, but is associated with a decrease of mitochondrial content of the cells that is correlated with an increase in LDH (and thus glycolytic) capacity.

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References

  1. Berthiaume F., MacDonald, A. D., Kang, Y. H., and Yarmush, M. L. (2003) Control analysis of mitochondrial metabolism in intact hepatocytes: effect of interleukin-1beta and interleukin-6. Metab. Eng. 5, 108–123.

    Article  PubMed  CAS  Google Scholar 

  2. Khan, A. U., Delude, R. L., Han, Y. Y., et al. (2002) Liposomal NAD(+) prevents diminished O(2) consumption by immunostimulated Caco-2 cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 282, L1082-L1091.

    PubMed  CAS  Google Scholar 

  3. Geng, Y., Hansson, G. K., and Holme, E. (1992) Interferon-gamma and tumor necrosis factor synergize to induce nitric oxide production and inhibit mitochondrial respiration in vascular smooth muscle cells. Circ. Res. 71, 1268–1276.

    PubMed  CAS  Google Scholar 

  4. Oddis, V. C. and Finkel, M. S. (1995) Cytokine-stimulated nitric oxide production inhibits mitochondrial activity in cardiac myocytes. Biochem. Biophys. Res. Commun. 213, 1002–1009.

    Article  PubMed  CAS  Google Scholar 

  5. Tatsumi, T., Matoba, S., Kawahara, A., et al. (2000) Cytokine-induced nitric oxide production inhibits mitochondrial energy production and impairs contractile function in rat cardiac myocytes. J. Am. Coll. Cardiol. 35, 1338–1346.

    Article  PubMed  CAS  Google Scholar 

  6. Carter, D., True, L., and Otis, C. N. (1997), Serous Membranes in Histology for Pathologists (Sternberg, S. S., ed.). Lippincott-Raven, New York, pp. 2299–2328.

    Google Scholar 

  7. Runyon, B. A. and Hillebrand, D. J. (1998) Surgical peritonitis and other diseases of the peritoneum, mesentery, omentum, and diaphragm, in: Sleisenger & Fordtran's Gastrointestinal and Liver Disease Pathophysiology, Diagnosis, Management (ed. 6) (Feldman, M., Scharschmidt, B. F., and Sleisenger, M. H., eds.). WB Saunders, Philadelphia, pp. 2035–2046.

    Google Scholar 

  8. Erroi, A., Sironi, M., Chiaffarino, F., Chen, Z. G., Mengozzi, M., and Mantovani, A. (1989) IL-1 and IL-6 release by tumor-associated macrophages from human ovarian carcinoma. Int. J. Cancer 44, 795–801.

    Article  PubMed  CAS  Google Scholar 

  9. Pruimboom, W. M., van Dijk, A. P., Tak, C. J., Bonta, I. L., Wilson, J. H., and Zijlstra, F. J. (1994) Production of inflammatory mediators by human macrophages obtained from ascites. Prostaglandins Leukot. Essent. Fatty Acids 50, 183–192.

    Article  PubMed  CAS  Google Scholar 

  10. Topley, N., Brown, Z., Joerres, A., et al. (1993) Human peritoneal mesothelial cells synthesize interleukin-8: synergistic induction by interleukin-1β and tumor necrosis factor-α. Am. J. Pathol. 142 1876–1886.

    PubMed  CAS  Google Scholar 

  11. Topley, N., Joerres, A., Luttmann, W., et al. (1993) Human peritoneal mesothelial cells synthesize interleukin-6: induction by IL-1β and TNF-α. Kidney Int. 43 226–233.

    Article  PubMed  CAS  Google Scholar 

  12. Offner, F. A., Obrist, P., Stadlmann, S., et al. (1995) IL-6 secretion by human peritoneal mesothelial and ovarian cancer cells. Cytokine 7, 542–547.

    Article  PubMed  CAS  Google Scholar 

  13. Offner, F. A., Feichtinger, H., Stadlmann, S., et al. (1996) Transforming growth factor-β synthesis by human peritoneal mesothelial cells—induction by interleukin-1. Am. J. Pathol. 148, 1679–1688.

    PubMed  CAS  Google Scholar 

  14. Cronauer, M. V., Stadlmann, S., Klocker, H., et al. (1999) Basic fibroblast growth factor synthesis by human peritoneal mesothelial cells: induction by interleukin-1. Am. J. Pathol. 15, 1977–1984.

    Google Scholar 

  15. Abendstein, B., Stadlmann, S., Knabbe, C., et al. (2000) Regulation of transforming growth factor-β secretion by human peritoneal mesothelial and ovarian carcinoma cells. Cytokine 12, 1115–1119.

    Article  PubMed  CAS  Google Scholar 

  16. Chen, J. Y., Chiu, J. H., Chen, H. L., Chen, T. W., Yang, W. C., and Yang, A. H. (2000) Human peritoneal mesothelial cells produce nitric oxide: induction by cytokines. Perit. Dial. Int. 20, 772–777.

    PubMed  CAS  Google Scholar 

  17. Gnaiger, E., Kuznetsov, A. V., Schneeberger, S., et al. (2000) Mitochondria in the cold, in Life in the Cold (Heldmaier, G. and Klingenspor, M., eds.). Springer, Heidelberg, pp. 431–442.

    Google Scholar 

  18. Winkelmeier, P., Glauner, B., and Lindl, T. (1993) Quantitation of cytotoxicity by cell volume and cell proliferation. ATLA 21, 269–280.

    Google Scholar 

  19. Gnaiger, E. (2001) Bioenergetics at low oxygen: dependence of respiration and phosphorylation on oxygen and adenosine diphosphate supply. Respir. Physiol. 128, 277–297.

    Article  PubMed  CAS  Google Scholar 

  20. Renner, K., Kofler, R., and Gnaiger, E. (2002) Mitochondrial function in glucocorticoid triggered T-ALL cells with transgenic Bcl-2 expression. Molec. Biol. Rep. 29, 97–101.

    Article  CAS  Google Scholar 

  21. Srere, P. A. (1969) Citrate synthase. Meth. Enzymol. 13, 3–11.

    Article  CAS  Google Scholar 

  22. Kuznetsov, A. V., Strobl, D., Ruttmann, E., Koenigsrainer, A., Margreiter, R., and Gnaiger E. (2002) Evaluation of mitochondrial respiratory function in small biopsies of liver. Anal. Biochem. 305, 186–194.

    Article  PubMed  CAS  Google Scholar 

  23. Bergmeier, H. U., ed. (1970) Methoden der enzymatischen Analyse (ed. 2). Akademie Verlag, Berlin.

    Google Scholar 

  24. Renner, K., Amberger, A., Konwalinka, G., Kofler, R., and Gnaiger, E. (2003) Changes of mitochondrial respiration, mitochondrial content and cell size after induction of apoptosis in leukemia cells. Biochim. Biophys. Acta 1642, 115–123.

    Article  PubMed  CAS  Google Scholar 

  25. Nisoli, E., Clementi, E., Paolucci, C., et al. (2003) Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science 299, 896–899.

    Article  PubMed  CAS  Google Scholar 

  26. Drapier, J. and Hibbs, J. B. (1988) Differentiation of murine macrophages to express nonspecific cytotoxicity for tumor cells results in l-arginine-dependent inhibition of mitochondrial iron-sulfur enzymes in the macrophage effector cells. J. Immunol. 140, 2829–2838.

    PubMed  CAS  Google Scholar 

  27. Tatsumi, T., Akashi, K., Keira, N., et al. (2004) Cytokine-induced nitric oxide inhibits mitochondrial energy production and induces myocardial dysfunction in endotoxin-treated rat hearts. J. Mol. Cell. Cardiol. 37, 775–784.

    Article  PubMed  CAS  Google Scholar 

  28. Wredenberg, A., Wibom, R., Wilhelmsson, H., et al. (2002) Increased mitochondrial mass in mitochondrial myopathy mice. Proc. Natl. Acad. Sci. U S A 99, 15066–15071.

    Article  PubMed  CAS  Google Scholar 

  29. Brand, M. D., Harper, M. E. and Taylor, H. C. (1993) Control of the effective P/O ratio of oxidative phosphorylation in liver mitochondria and hepatocytes. Biochem. J. 291, 739–748.

    PubMed  CAS  Google Scholar 

  30. Kruse, M., Mahiout, A., Kliem, V., Kurz, P., Koch, K. M., and Brunkhorst, R. (1996) Interleukin-1beta stimulates glucose uptake of human peritoneal mesothelial cells in vitro. Perit. Dial. Int. 16, S58-S60.

    PubMed  Google Scholar 

  31. Taylor, D. J., Whitehead, R. J., Evanson, J. M., et al. (1988) Effect of recombinant cytokines on glycolysis and fructose 2,6 biphosphate in rheumatoid synovial cells in vitro. Biochem. J. 250, 111–115.

    PubMed  CAS  Google Scholar 

  32. Bird, T. A., Davies, A., Baldwin, S. A., and Saklatvala, J. (1990) Interleukin 1 stimulates hexose transport in fibroblasts by increasing the expression of glucose transporters. J. Biol. Chem. 265, 13578–13583.

    PubMed  CAS  Google Scholar 

  33. Hernvann, A., Aussel, C., Cynober, L., Moatti, N., and Ekindjian, O. G. (1992) IL-1beta, a strong mediator for glucose uptake by rheumatoid and non-rheumatoid cultured human synoviocytes. FEBS Lett. 303, 77–80.

    Article  PubMed  CAS  Google Scholar 

  34. Ben-Shlomo, I., Kol, S., Roeder, L. M., et al. (1997) Interleukin (IL)-1b increases glucose uptake and induces glycolysis in aerobically cultured rat ovarian cells: evidence that IL-1β may mediate the gonadotropin-induced midcycle metabolic shift. Endocrinology 138, 2680–2688.

    Article  PubMed  CAS  Google Scholar 

  35. Berg, S., Sappington, P. L., Guzik, L. J., Delude, R. L., and Fink, M. P. (2003) Proinflammatory cytokines increase the rate of glycolysis and adenosine-5′-triphosphate turnover in cultured rat enterocytes. Crit. Care Med. 31, 1203–1212.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Erich Gnaiger.

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Stadlmann, S., Renner, K., Pollheimer, J. et al. Preserved coupling of oxidative phosphorylation but decreased mitochondrial respiratory capacity in IL-1β-treated human peritoneal mesothelial cells. Cell Biochem Biophys 44, 179–186 (2006). https://doi.org/10.1385/CBB:44:2:179

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