Mycoplasma fermentans—Induced Inflammatory Response of Astrocytes: Selective Modulation by Aminoguanidine, Thalidomide, Pentoxifylline and IL-10
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Exposure of primary rat glial cells, mostly astrocytes, to heat-inactivated Mycoplasma fermentans triggers the production of tumor necrosis factor α (TNFα) nitric oxide (NO) and prostaglandin E2 (PGE2). To attenuate the production of these proinflammatory mediators, four agents: aminoguanidine, pentoxifylline, thalidomide and IL-10 were added to astrocyte cultures. Aminoguanidine (1 and 3 mM), an inhibitor of inducible nitric oxide synthase (iNOS), suppressed the production of the three mediators. TNFα was the most sensitive to thalidomide, showing dose-response inhibition at concentrations of 20 μg/ml, 50 μg/ml and 250 μg/ml. PGE2 was affected only by concentrations of 50 μg/ml and 250 μg/ml, whereas NO responded solely to the highest amount of this inhibitor. The cytokine IL-10, at 10 U and 50 U, inhibited only TNFα production. Our results imply that selective suppression of proinflammatory mediators by various agents may prove feasible for amelioration of central nervous system inflammatory diseases.
- Razin, S. and J. G. Tully. 1995. In: Molecular and Diagnostic Procedures in Mycoplasmology. Vol. 1 Molecular characterization. pp 1-25, Academic Press. San Diego, New York, Boston, London, Sydney, Tokyo, Toronto.
- Gabridge, M. G., K. F. Candler, and M. Daniels. 1985. In: The Mycoplasmas. Vol. 4. Academic Press, New York, pp 312-352.
- Casswell, G. H. and B. C. Cole. 1981, Mycoplasmas as agents of human disease. N. Engl. J. Med. 304, 80-89.
- Gallily, R., T. Sher, P. Ben-Av, and J. Loewenstein. 1989, Tumor necrosis factor as a mediator of Mycoplasma orale-induced tumor cell lysis by macrophages. Cellular Immunology, 121, 146-153.
- Gallily, R., M. Salman, M. Tarshis, and S. Rottem. 1992, Mycoplasma fermentans (incognitus strain) induces TNFα and IL-1 production by human monocytes and murine macrophages. Immunology Letters, 34, 27-30.
- Rosendal, S., S. Levisohn, and R. Gallily. 1995, Cytokines induced in vitro by Mycoplasma mycoides ssp. Mycoides, large colony type. Veterinary Immunol. and Immunopathology, 44, 269-278.
- Avron, A. and R. Gallily. 1995. Mycoplasma stimulates the production of oxidative radicals by murine peritoneal macrophages. J. Leuk. Biol. 57, 264-268.
- Brenner, T., A. Yamin, O. Abramsky, and R. Gallily. 1993. Stimulation of tumor necrosis factor-α production by mycoplasms. Brain Research 608, 273-279.
- Brenner, T., A. Yamin, and R. Gallily, 1994. Mycoplasma triggering of nitric oxide production by central nervous system glial cells and its inhibition by glucocorticoids. Brain Research, 641, 51-56.
- Lo, S. C., M. S. Dawson, D. M. Wong, P. B. Newton, M. A. Somda, W. F. Engler, R. Y. H. Wand, J. W. K. Shin, H. J. Alter, and D. J. Wear. 1989. Identification of Mycoplasma incognitus infection in a patient with AIDS, an immunohistochemical, in situ hybridization and ultrastructural study. Am. J. Top. Med. Hyg. 41, 601-616.
- Maimone, D., S. Gregory, B. G. W. Arnason, and A. T. Regar, 1991. Cytokine levels in cerebrospinal fluid and serum of patients with multiple sclerosis. J. Neuroimmunol, 32, 601-616.
- Price, R. W., B. Brew, J. Siditis, M. Rosenblum, A. C. Scheck, and P. Cleary, 1988. The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science, 239, 586-592.
- Brenner, T., S. Brocke, F. Szater, R. A. Sober, J. F. Parkinson, D. H. Perez, and L. Steinman, 1997, Inhibition of nitric oxide synthase for treatment of experimental autoimmune encephalomyelitis. J. Immunol. 158, 2940-2941.
- Sampaio, E. P., E. N. Sarno, R. Gallily, Z. A. Cohn, and G. Kaplan. 1991, Thalidomide selectively inhibits tumor necrosis factor α production by stimulated human monocytes. J. Exp. Med., 173, 699-703.
- Tilg, H., B. Eibl, M. Pihl, A. GÄchter, M. Herold, J. Brankova, C. Huber, and D. Niederwieser. 1993, Immune response modulation by pentoxifylline in vitro. Transplantation, 56, 196-201.
- Moore, K. W., A. O'Garra, Pene de Waal Malefy, P. Vieira, and T. R. Mosmann. 1993. Interleukin 10, Annu. Rev. Immunol. 11, 165-190.
- Brenner, T., R. P. Lisak, A. Rostami, D. E. Pleasure, and D. H. Silberberg. 1986, Astrocytes, oligodendrocytes and Schwann cells share a common antigenic determinant that cross-reacts with myelin basic protein: identification with monoclonal antibody. J. Neurosci. 6, 1925-1933.
- Amit, Y. and T. Brenner. 1993. Age-dependent sensitivity of cultured rat glial cells to bilirubin toxicity. Exp. Neurol. 121, 248-255.
- Sher, T., S. Rottem, and R Gallily. 1990. Mycoplasma capricolum membranes induce tumor necrosis factor by a mechanism different from that of lipopolysaccharide. Cancer Immunol. Immunother., 31, 86-92.
- Bogdan, C., Y. Vodovotz, and C. Nathan. 1991. Macrophage de-activation by interleukin-10. J. Exp. Med., 174, 1549-1555.
- Lalani, I., K. Bhol, and A. R. Ahmed. 1997, Interleukin-10, biology, role in inflammation and autoimmunity. Ann. Allergy-Asthma-Immunol., 79, 469-483.
- Bo, L., T. M. Dawson, S. Wesselingh, S. Mork, S. Choi, P. A. Kong, D. Hanley, and B. D. Trapp. 1994, Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains. Ann. Neurol. 36, 778-786.
- Oliver, S. J., T. P. Cheng, M. L. Banquerigo, and E. Brahn. 1988. The effect of thalidomide and 2 analogs on collagen-induced arthritis. J. Rheumatol. 25, 964-967.
- Klausner, J. F., V. H. Freedman, and G. Kaplan. 1996. Thalidomide as an anti-TNF alpha inhibitor: Implication for clinical use. Clin. Immunol. Immunopathol., 8, 219-223.
- Moeira, A. L., E. P. Sampaio, A. Zmuidzinas, P. Frindt, K. A., Smith, and G. Kaplan. 1993. Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J. Exp. Med., 177, 1675-1680.
- Han, J., P. Thompson, and B. Beutler. 1990. Dexamethasone and pentoxifylline inhibit endotoxin induced cachectin/tumor necrosis factor synthesis at separate points in the signaling pathway. J. Exp. Med., 172, 391-394.
- Schmidt-Cloudhury, A., G. T. Furuta, J. A. Lavigne, S. J. Galli, and B. K. Wershil, 1996. The regulation of tumor necrosis factor production in murine mast cells: pentoxifylline or dexamathasone inhibits IgE-dependent production of the TNF-alpha by distinct mechanisms. Cell. Immunol., 171, 140-146.
- Bogdan, C., Y. Vodovotz and C. Nathan, 1991. Macrophage deactivation by interleukin 10. J. Exp. Med., 174, 1549-1555.
- Wang, P., P. Wu, M. I. Siegel, R. W. Egan, and M. M. Billah, 1995. Interleukin (IL) 10 inhibits nuclear factor β (NF Kappa B) activation in human monocytes. IL-10 and IL-4 suppress cytokine synthesis by different mechanisms. J. Biol. Chem., 270, 9558-9582.
- Shri Kant, P., and E. N. Benveniste, 1996. The central nervous system as an immunocompetent organ. J. Immunol. 157, 1819-1822.
- Mycoplasma fermentans—Induced Inflammatory Response of Astrocytes: Selective Modulation by Aminoguanidine, Thalidomide, Pentoxifylline and IL-10
Volume 23, Issue 6 , pp 495-505
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- 1. The Lautenberg Center for General and Tumor Immunology, Hadassah Medical School, Hebrew University, Israel
- 2. Laboratory of Neuroimmunology, Department of Neurology, Hadassah University Hospital, Jerusalem, 91120, Israel