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A metalloporphyrin-based superoxide dismutase mimic inhibits adoptive transfer of autoimmune diabetes by a diabetogenic T-cell clone.

Publication ,  Journal Article
Piganelli, JD; Flores, SC; Cruz, C; Koepp, J; Batinic-Haberle, I; Crapo, J; Day, B; Kachadourian, R; Young, R; Bradley, B; Haskins, K
Published in: Diabetes
February 2002

We present here the first report of a metalloporphyrin-based antioxidant that can prevent or delay the onset of autoimmune diabetes. Type 1 diabetes is an autoimmune process whereby T-cells recognize pancreatic beta-cell antigens and initiate a leukocyte infiltrate that produces proinflammatory cytokines and reactive oxygen species (ROS), ultimately leading to beta-cell destruction. Because islet beta-cells have a reduced capacity to scavenge free radicals, they are very sensitive to ROS action. Metalloporphyrin-based superoxide dismutase (SOD) mimics scavenge ROS and protect cells from oxidative stress and apoptosis. To investigate the effect of SOD mimics and the role of oxidative stress in the development of autoimmune diabetes in vivo, we used a diabetogenic T-cell clone, BDC-2.5, to induce rapid onset of diabetes in young nonobese diabetic-severe combined immunodeficient mice (NOD.scid). Disease was significantly delayed or prevented altogether by treatment of recipient mice with an SOD mimic, AEOL-10113, before transfer of the BDC-2.5 clone. To investigate the mechanisms of protection, in vitro assays for T-cell proliferation and gamma-interferon (IFN-gamma) production were carried out using the T-cell clone BDC-2.5. We found that the SOD mimic significantly inhibited antigen-presenting cell-dependent T-cell proliferation and IFN-gamma production in vitro. In addition, pretreatment of lipopolysaccharide (LPS)-stimulated peritoneal macrophages with SOD mimic inhibited the LPS-dependent increase in TNF-alpha as well as the NADPH oxidase-dependent release of superoxide. Finally, this compound protected NIT-1 insulinoma cells from interleukin-1beta and alloxan cytotoxicity in vitro.

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Published In

Diabetes

DOI

ISSN

0012-1797

Publication Date

February 2002

Volume

51

Issue

2

Start / End Page

347 / 355

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Respiratory Burst
  • Receptors, Antigen, T-Cell
  • Mice, SCID
  • Mice, Inbred NOD
  • Mice
  • Metalloporphyrins
  • Lipopolysaccharides
  • Interferon-gamma
  • Insulinoma
 

Citation

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Chicago
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Piganelli, J. D., Flores, S. C., Cruz, C., Koepp, J., Batinic-Haberle, I., Crapo, J., … Haskins, K. (2002). A metalloporphyrin-based superoxide dismutase mimic inhibits adoptive transfer of autoimmune diabetes by a diabetogenic T-cell clone. Diabetes, 51(2), 347–355. https://doi.org/10.2337/diabetes.51.2.347
Piganelli, Jon D., Sonia C. Flores, Coral Cruz, Jeffrey Koepp, Ines Batinic-Haberle, James Crapo, Brian Day, et al. “A metalloporphyrin-based superoxide dismutase mimic inhibits adoptive transfer of autoimmune diabetes by a diabetogenic T-cell clone.Diabetes 51, no. 2 (February 2002): 347–55. https://doi.org/10.2337/diabetes.51.2.347.
Piganelli JD, Flores SC, Cruz C, Koepp J, Batinic-Haberle I, Crapo J, et al. A metalloporphyrin-based superoxide dismutase mimic inhibits adoptive transfer of autoimmune diabetes by a diabetogenic T-cell clone. Diabetes. 2002 Feb;51(2):347–55.
Piganelli, Jon D., et al. “A metalloporphyrin-based superoxide dismutase mimic inhibits adoptive transfer of autoimmune diabetes by a diabetogenic T-cell clone.Diabetes, vol. 51, no. 2, Feb. 2002, pp. 347–55. Pubmed, doi:10.2337/diabetes.51.2.347.
Piganelli JD, Flores SC, Cruz C, Koepp J, Batinic-Haberle I, Crapo J, Day B, Kachadourian R, Young R, Bradley B, Haskins K. A metalloporphyrin-based superoxide dismutase mimic inhibits adoptive transfer of autoimmune diabetes by a diabetogenic T-cell clone. Diabetes. 2002 Feb;51(2):347–355.

Published In

Diabetes

DOI

ISSN

0012-1797

Publication Date

February 2002

Volume

51

Issue

2

Start / End Page

347 / 355

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Respiratory Burst
  • Receptors, Antigen, T-Cell
  • Mice, SCID
  • Mice, Inbred NOD
  • Mice
  • Metalloporphyrins
  • Lipopolysaccharides
  • Interferon-gamma
  • Insulinoma