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Synergistic effects of thalidomide and poly(ADP-ribose) polymerase inhibition on type II collagen-induced arthritis in mice

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Abstract

The present study investigates synergistic effects of the TNF-α inhibitor thalidomide and the poly(ADP-ribose) polymerase (PARP)-inhibitor nicotinic acid amide (NAA) in male DBA/1 hybrid mice suffering from type II collagen-induced arthritis. Parameters including the arthritis index, chemiluminescence and anti-collagen antibody titers were used for the assessment of disease activity: The disease courses demonstrated clearly an inhibitory effect of thalidomide. NAA inhibited established collagen arthritis in a dose-dependent manner. The combined application of thalidomide and NAA caused a powerful synergistic inhibition of arthritis. Furthermore, thalidomide and NAA were tested ex vivo for their inhibition of the NADPH oxidase-dependent generation of reactive oxygen species by activated neutrophils and monocytes in unseparated human blood. Our data show that type II collagen-induced arthritis can be suppressed by the simultaneous inhibition of TNF-α, PARP, and NADPH oxidase.

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Abbreviations

NAA:

nicotinic acid amide

PARP:

poly(ADP-ribose) polymerase (EC 2.4.2.30)

Thal:

thalidomide (α-phthalimidoglutarimide, racemic mixture of R-(+)- and S-(−)-enantiomer)

TNF-α :

tumor necrosis factor alpha

CIA:

type II collagen-induced arthritis

CL:

chemiluminescence

cph:

counts per hour

TPA:

12-O-tetradecanoylphorbol 13-acetate

ROS:

reactive oxygen species

IL:

interleukin

IFN:

interferon

TGF:

transforming growth factor

GM-CSF:

granulocyte-macrophage colony-stimulating factor

NO:

nitric oxide

References

  1. Gutiérrez-Rodriguez, O., P. Starusta-Bacal, andO. Gutiérrez-Montes. 1989. Treatment of refractory rheumatoid arthritis-the thalidomide experience.J. Rheumatol. 16:158–163.

    PubMed  Google Scholar 

  2. Atra, E., andE. I. Sato. 1993. Treatment of the cutaneous lesions of systemic lupus erythematosus with thalidomide.Clin. Exp. Rheumatol. 11:487–493.

    PubMed  Google Scholar 

  3. Schwinghammer, T. L., andE. J. Bloom. 1993. Pharmacologic prophylaxis of acute graftversus-host disease after allogeneic marrow transplantation.Clin. Pharm. 12:736–761.

    PubMed  Google Scholar 

  4. Handley, J., M. Shields, J. Dodge, M. Walsh, andA. Bingham. 1993. Chronic bullous disease of childhood and ulcerative colitis.Pediat. Dermatol. 10:256–258.

    Google Scholar 

  5. Makonkawkeyoon, S., R. N. R. Limson-Pobre, A. L. Moreira, V. Schauf, andG. Kaplan. 1993. Thalidomide inhibits the replication of human immunodeficiency virus type 1.Proc. Natl. Acad. Sci. U.S.A. 90:5974–5978.

    PubMed  Google Scholar 

  6. Kaplan, G.. 1993. Recent advances in cytokine therapy in leprosy.J. Infect. Dis. 167(Suppl.l):S18–22.

    PubMed  Google Scholar 

  7. Ehninger, G., K. Eger, A. Stuhler, andU. Schuler. 1993. Thalidomide-the need for a new clinical evaluation of an old drug.Bone Marrow Transplant. 12(Suppl. 3):S26–28.

    PubMed  Google Scholar 

  8. Moreira, A. L., E. P. Sampaio, A. Zmuidzinas, P. Frindt, K. A. Smith, andG. Kaplan. 1993. Thalidomide exerts its inhibitory action on tumor necrosis factorα by enhancing mRNA degradation.J. Exp. Med. 177:1675–1680.

    PubMed  Google Scholar 

  9. Elliott, M. J., R. N. Maini, M. Feldmann, A. Long-Fox, P. Charles, andF. M. Brennan. 1993. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to TNFα. Safety, clinical efficacy and regulation of the acute-phase response.Brit. J. Rheumatol. 32 (Abstracts Suppl. 1): 107.

    Google Scholar 

  10. Keffer, J., L. Probert, H. Cazlaris, S. Georgopoulos, E. Kaslaris, D. Kioussis, andG. Kollias. 1991. Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis.EMBO J. 10:4025–4031.

    PubMed  Google Scholar 

  11. Kröger, H., R. Miesel, W. Ehrlich, andM. Kurpisz. 1994. Arthritogenic mechanisms of deregulated poly-ADP-ribosylation in experimental models of arthritis.Z. Rheumotol. 53(Suppl. 1):59.

    Google Scholar 

  12. Miesel, R., M. Kurpisz, andH. Kröger. 1995. Modulation of inflammatory arthritis by inhibition of poly(ADP-ribose) polymerase.Inflammation 19:379–387.

    PubMed  Google Scholar 

  13. Kröger, H., A.Dietrich, M.Ohde, and R.Miesel. 1995. Influence of antagonists of poly(ADP-ribose) polymerase on the development of collagen II induced arthritis. Submitted.

  14. Miesel, R., H. Kröger, M. Zuber, R. Grätz, andJ. Neth. 1994. Elevated levels of oxygenand nitrogen-centered radicals in patients with inflammatory and autoimmune rheumatic diseases.Z. Rheumatol. 53(Suppl. 1):6.

    Google Scholar 

  15. DeMurcia, G., M. Jacobson, andS. Shall. 1995. Regulation by ADP-ribosylation.Trends Cell Biol. 5:78–81.

    PubMed  Google Scholar 

  16. Miesel, R., M.Zuber, R.Hartung, and H.Kröger. 1995. Total radical trapping antioxidative capacity of plasma and whole blood chemiluminescence in patients with inflammatory and autoimmune rheumatic diseases.Redox Report, in press.

  17. Carson, D. A., S. Seto, andD. B. Wasson. 1986. Lymphocyte dysfunction after DNA damage by toxic oxygen species.J. Exp. Med. 163:746–751.

    PubMed  Google Scholar 

  18. Sibley, J. T., R. P. Braun, andJ. S. Lee. 1986. The production of antibodies to DNA in normal mice following immunization with poly(ADP-ribose).Clin. Exp. Immunol. 64:563–569.

    PubMed  Google Scholar 

  19. Kanai, Y., Y. Kawaminami, M. Miwa, T. Matsushima, T. Sugimura, Y. Moroi, andR. Yokohari. 1977. Naturally-occurring antibodies to poly(ADP-ribose) in patients with systemic lupus erythematosus.Nature 265:175–177.

    PubMed  Google Scholar 

  20. Agarwal, S., andN. P. Piesco. 1994. Poly ADP-ribosylation of a 90-kDa protein is involved in TNF-α-mediated cytotoxicity.J. Immunol. 153:473–481.

    PubMed  Google Scholar 

  21. Pellat-Deceunynck, C., J. Wietzerbin, andJ. C. Drapier. 1994. Nicotinamide inhibits nitric oxide synthase mRNA induction in activated macrophages.Biochem. J. 297:53–58.

    PubMed  Google Scholar 

  22. Shockett, P., andJ. Stavnezer. 1993. Inhibitors of poly(ADP-ribose) polymerase increase antibody class switching.J. Immunol. 151:6962–6976.

    PubMed  Google Scholar 

  23. Ayer, L. M., S. M. Edworthy, andM. J. Fritzler. 1993. Effect of procainamide and hydralazine on poly(ADP-ribosylation) in cell lines.Lupus 2:167–172.

    PubMed  Google Scholar 

  24. Halldórsson, H., T. Bödvarsdóttir, M. Kjeld, andG. Thorgeirsson. 1992. Role of ADP-ribosylation in endothelial signal transduction and prostacyclin production.FEBS Lett. 314:322–326.

    PubMed  Google Scholar 

  25. Miesel, R., A. Dietrich, B. Brandl, N. Ulbrich, M. Kurpisz, andH. Kröger. 1994. Suppression of arthritis by an active center analogue of Cu2Zn2-superoxide dismutase.Rheumatol. Int. 14:119–126.

    PubMed  Google Scholar 

  26. Miesel, R., A. Dietrich, N. Ulbrich, H. Kröger, andN. A. Mitchison. 1994. Assessment of collagen type II induced arthritis in mice by whole blood chemiluminescence.Autoimmunity 19:153–159.

    PubMed  Google Scholar 

  27. Boissier, M. C., G. Chiocchia, M. C. Ronziere, D. Herbage, andC. Fournier. 1990. Arthritogenicity of minor cartilage collagens (types IX and XI) in mice.Arthritis Rheum. 33: 1–8.

    PubMed  Google Scholar 

  28. Wooley, P. H., H. S. Luthra, J. M. Stuart, andC. S. David. 1981. Type II collagen-induced arthritis in mice.J. Exp. Med. 154:688–700.

    PubMed  Google Scholar 

  29. Miesel, R., H. Kröger, M. Kurpisz, andU. Weser. 1995. Induction of arthritis in mice and rats by potassium peroxochromate and assessment of disease activity by whole blood chemiluminescence and99mpertechnetate-imaging.Free Radical Res. 23:213–227.

    Google Scholar 

  30. Dietrich, A., N. A. Mitchison, E. Rajnavölgyi, andS. C. Schneider. 1994. Primed lymphocytes are boosted by type II collagen of their hosts after adoptive transfer.J. Autoimmunity 7:601–609.

    Google Scholar 

  31. Marcus, R., andA. M. Coulston. 1985. Nicotinic acid.In The pharmacological basis of therapeutics. A. Goodman A. Gilman, L. S. Goodman, T. W. Rall, and F. Murad, editors. 7th edition. Macmillan, New York. 1557–1559.

    Google Scholar 

  32. Wooley, P. H. 1988. Collagen-induced arthritis in the mouse.Methods Enzymol. 162:361–373.

    PubMed  Google Scholar 

  33. Mellin, G. W., andM. Katzenstein. 1962. The saga of thalidomide.N. Engl. J. Med. 267:1184–1193.

    PubMed  Google Scholar 

  34. Moncada, B., M. L. Baranda, R. González-Amaro, R. Urbina, andC. E. Loredo. 1985. Thalidomide-effect on T cell subsets as a possible mechanism of action.Int. J. Lepr. 53:201–205.

    Google Scholar 

  35. Vogelsang, G. B., S. Taylor, G. Gordon, andA. D. Hess. 1986. Thalidomide, a potent agent for the treatment of graft-versus-host disease.Transplant. Proc. 18:904–906.

    Google Scholar 

  36. Blaschke, G.. 1986. Chromatographic resolution of chiral drugs on polyamides and cellulose triacetate.J. Liq. Chromatogr. 9:341–368.

    Google Scholar 

  37. Teixeira, F., M. T. Hojyo, R. Arenas, M. E. Vega, R. Cortes, A. Ortiz, andL. Dominguez. 1994. Thalidomide: can it continue to be used?Lancet 344:196–197.

    Google Scholar 

  38. Nishimura, K., Y. Hashimoto, andS. Iwasaki. 1994. Enhancement of phorbol ester-induced production of tumor necrosis factorα by thalidomide.Biochem. Biophys. Res. Commun. 199:455–460.

    PubMed  Google Scholar 

  39. Gupta, J. W., M. Kubin, L. Hartman, M. Cassatella, andG. Trinchieri. 1992. Induction of expression of genes encoding components of the respiratory burst oxidase during differentiation of human myeloid cell lines induced by tumor necrosis factor andγ-interferon.Cancer Res. 52:2530–2537.

    PubMed  Google Scholar 

  40. Ambruso, D. R., B. G. J. M. Bolscher, P. M. Stokman, A. J. Verhoeven, andD. Roos. 1990. Assembly and activation of the NADPH:O2 oxidoreductase in human neutrophils after stimulation with phorbol myristate acetate.J. Biol. Chem. 265:924–930.

    PubMed  Google Scholar 

  41. Gordon, G. B., S. P. Spielberg, D. A. Blake, andV. Balasubramanian. 1981. Thalidomide teratogenesis: Evidence for a toxic arene oxide metabolite.Proc. Natl. Acad. Sci. U.S.A. 78:2545–2548.

    PubMed  Google Scholar 

  42. Altmann, H.. 1983. Poly-(ADP-Ribose-)Synthese und Regulationsstörungen bei Erkrankungen.Wien. klin. Wschr. 95:861–864.

    PubMed  Google Scholar 

  43. Miller, E. J., andR. K. Rhodes. 1982. Preparation and characterization of the different types of collagen.Methods Enzymol. 82:33–64.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, German Rheumatology Research Center, Berlin, Germany

    Hans Kröger, Ralf Miesel, Annette Dietrich, Manuela Ohde & Eva Rajnavölgyi

  2. Department of Biochemistry, University of Otago, Dunedin, New Zealand

    Ralf Miesel

  3. Department of Physiological Chemistry, University of Ulm, Ulm, Germany

    Heinrich Ockenfels

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Kröger, H., Miesel, R., Dietrich, A. et al. Synergistic effects of thalidomide and poly(ADP-ribose) polymerase inhibition on type II collagen-induced arthritis in mice. Inflammation 20, 203–215 (1996). https://doi.org/10.1007/BF01487406

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