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.
Similar content being viewed by others
References
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Winkelmeier, P., Glauner, B., and Lindl, T. (1993) Quantitation of cytotoxicity by cell volume and cell proliferation. ATLA 21, 269–280.
Gnaiger, E. (2001) Bioenergetics at low oxygen: dependence of respiration and phosphorylation on oxygen and adenosine diphosphate supply. Respir. Physiol. 128, 277–297.
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.
Srere, P. A. (1969) Citrate synthase. Meth. Enzymol. 13, 3–11.
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.
Bergmeier, H. U., ed. (1970) Methoden der enzymatischen Analyse (ed. 2). Akademie Verlag, Berlin.
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.
Nisoli, E., Clementi, E., Paolucci, C., et al. (2003) Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science 299, 896–899.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
Contributed equally to this work.
For papers with multiple authorship, the asterisk identifies the author to whom correspondence and reprint requests should be addressed.
Rights and permissions
About this article
Cite this article
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
Issue Date:
DOI: https://doi.org/10.1385/CBB:44:2:179