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Research ArticleArticle

Antieosinophilic Activity of Orazipone

Hannu Kankaanranta, Pinja Ilmarinen, Xianzhi Zhang, Erkki Nissinen and Eeva Moilanen
Molecular Pharmacology June 2006, 69 (6) 1861-1870; DOI: https://doi.org/10.1124/mol.105.021170
Hannu Kankaanranta
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Pinja Ilmarinen
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Xianzhi Zhang
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Erkki Nissinen
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Eeva Moilanen
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Abstract

Orazipone is a novel sulfhydryl-reactive compound that has been previously shown to reduce lung eosinophilia in guinea pigs and rats and to inhibit degranulation in mast cells and cytokine production in monocytes and T-cells. However, the effects of orazipone on granulocyte longevity are unknown. Orazipone and its derivative 3-(4-chloro-3-nitro-benzylidene)-pentane-2,4-dione (OR-2370) reversed interleukin-5-afforded survival of human eosinophils by inducing apoptosis. In contrast, orazipone did not affect granulocyte macrophage-colony-stimulating factor-induced survival of human neutrophils. The effect of orazipone on eosinophil apoptosis is different from that of glucocorticoids in that even high con-centrations of interleukin-5 were not able to overcome the effect of orazipone. Orazipone further enhanced spontaneous apoptosis as well as that induced by CD95 ligation without inducing primary necrosis. OR-2370-induced DNA fragmentation was shown to be dependent on caspases 3 and 6 and c-jun-N-terminal kinase, whereas extracellular regulated kinase, p38 mitogen-activated protein kinase, and phosphatidylinositol 3-kinase as well as caspases 4, 8, and 9 seem not to mediate its actions. Our results suggest that orazipone and its derivative OR-2370 possess strong antieosinophilic activity and thus may have anti-inflammatory efficacy in the treatment of asthma and/or allergic conditions.

  • Received November 25, 2005.
  • Accepted March 15, 2006.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 69 (6)
Molecular Pharmacology
Vol. 69, Issue 6
1 Jun 2006
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Research ArticleArticle

Antieosinophilic Activity of Orazipone

Hannu Kankaanranta, Pinja Ilmarinen, Xianzhi Zhang, Erkki Nissinen and Eeva Moilanen
Molecular Pharmacology June 1, 2006, 69 (6) 1861-1870; DOI: https://doi.org/10.1124/mol.105.021170

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Research ArticleArticle

Antieosinophilic Activity of Orazipone

Hannu Kankaanranta, Pinja Ilmarinen, Xianzhi Zhang, Erkki Nissinen and Eeva Moilanen
Molecular Pharmacology June 1, 2006, 69 (6) 1861-1870; DOI: https://doi.org/10.1124/mol.105.021170
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