Cobalt protoporphyrine IX-mediated heme oxygenase-I induction alters the inflammatory cytokine response, but not antigen presentation after experimental allogeneic bone marrow transplantation

  • Authors:
    • Patricia Ewing
    • Gerhard C. Hildebrandt
    • Simone Planke
    • Reinhard Andreesen
    • Ernst Holler
    • Armin Gerbitz
  • View Affiliations

  • Published online on: September 1, 2007     https://doi.org/10.3892/ijmm.20.3.301
  • Pages: 301-308
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Abstract

Acute graft-versus-host disease (aGvHD) remains the major cause of mortality after allogeneic stem cell transplantation. Acute GvHD can be partially prevented when heme oxygenase-1 (HO-1) is induced in the recipient prior to transplantation but the mechanisms are not fully understood. Using a murine haploidentical bone marrow transplantation (BMT) model (C57Bl/6↷B6D2F1) we tested whether HO-1 induction altered the alloreactive T cell response or rather modulated the inflammatory cytokine profile early after BMT. In vivo administration of cobalt protoporphyrine IX (CoPP) did not affect the expression of MHC class I and II or the costimulatory molecules CD80 and CD86 on murine peritoneal and on splenic dendritic cells (DCs). Allospecific T cell proliferation and interferon γ secretion did not differ in mixed lymphocyte reactions using either CoPP-pretreated allogeneic recipients or control-treated DCs as stimulators. Furthermore, splenic DCs, isolated one to four days after BMT from CoPP-pretreated recipients did not show any differences in the expression of costimulatory molecules compared to untreated controls, and T cell expansion and the cytolytic capacity 14 days after BMT were equal in the control and CoPP-treated allogeneic groups. Serum tumor necrosis factor α levels were significantly reduced in CoPP-treated allogeneic recipients when compared to allogeneic controls and did not differ from the syngeneic recipients. Our results indicate that the protective effects of CoPP-mediated HO-1 induction on survival and aGvHD after allogeneic BMT involve a reduction in the proinflammatory cytokine milieu rather than alteration in allospecific T cell stimulation.

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September 2007
Volume 20 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Ewing P, Hildebrandt GC, Planke S, Andreesen R, Holler E and Gerbitz A: Cobalt protoporphyrine IX-mediated heme oxygenase-I induction alters the inflammatory cytokine response, but not antigen presentation after experimental allogeneic bone marrow transplantation. Int J Mol Med 20: 301-308, 2007
APA
Ewing, P., Hildebrandt, G.C., Planke, S., Andreesen, R., Holler, E., & Gerbitz, A. (2007). Cobalt protoporphyrine IX-mediated heme oxygenase-I induction alters the inflammatory cytokine response, but not antigen presentation after experimental allogeneic bone marrow transplantation. International Journal of Molecular Medicine, 20, 301-308. https://doi.org/10.3892/ijmm.20.3.301
MLA
Ewing, P., Hildebrandt, G. C., Planke, S., Andreesen, R., Holler, E., Gerbitz, A."Cobalt protoporphyrine IX-mediated heme oxygenase-I induction alters the inflammatory cytokine response, but not antigen presentation after experimental allogeneic bone marrow transplantation". International Journal of Molecular Medicine 20.3 (2007): 301-308.
Chicago
Ewing, P., Hildebrandt, G. C., Planke, S., Andreesen, R., Holler, E., Gerbitz, A."Cobalt protoporphyrine IX-mediated heme oxygenase-I induction alters the inflammatory cytokine response, but not antigen presentation after experimental allogeneic bone marrow transplantation". International Journal of Molecular Medicine 20, no. 3 (2007): 301-308. https://doi.org/10.3892/ijmm.20.3.301