Glycogen synthase kinase-3β inhibition attenuates the development of bleomycin-induced lung injury

Salvatore Cuzzocrea, T. Genovese, E. Mazzon, E. Esposito, C. Muià, M. Abdelrahman, R. Di Paola, P. Bramanti, C. Thiemermann

Research output: Contribution to journalArticle

Abstract

Glycogen synthase kinase-3 (GSK-3) is an ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and has recently been implicated in the pathophysiology of a number of diseases. The aim of this study is to investigate the effects of TDZD-8, a potent and selective GSK-3β inhibitor, on the development of lung injury caused by administration of bleomycin (BLM). Mice subjected to intra-tracheal administration of BLM developed significant lung injury characterized by marked neutrophil infiltration and tissue edema. An increase in immunoreactivity to nitrotyrosine, iNOS, TNF-α and IL-1β was also observed in the lungs of BLM-treated mice. In contrast, administration of BLM-treated mice with TDZD-8 (1 mg/kg daily) significantly reduced (I) the degree of lung injury, (II) the increase in staining (immunohistochemistry) for myeloperoxidase (MPO), nitrotyrosine, iNOS, TNF-α and IL-1β and (III) the degree of apoptosis, as evaluated by Bax and Bcl-2 immunoreactivity and TUNEL staining. Taken together, these results clearly demonstrate treatment with the GSK-3β inhibitor TDZD-8 reduces the development of lung injury and inflammation induced by BLM in mice.

Original languageEnglish
Pages (from-to)619-630
Number of pages12
JournalInternational Journal of Immunopathology and Pharmacology
Volume20
Issue number3
Publication statusPublished - Jul 2007

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Keywords

  • Bleomycin
  • Cytokines
  • Glycogen synthase kinase-3 (GSK-3)
  • Inflammation
  • Neutrophil infiltration
  • Signal transduction

ASJC Scopus subject areas

  • Pharmacology

Cite this

Cuzzocrea, S., Genovese, T., Mazzon, E., Esposito, E., Muià, C., Abdelrahman, M., Di Paola, R., Bramanti, P., & Thiemermann, C. (2007). Glycogen synthase kinase-3β inhibition attenuates the development of bleomycin-induced lung injury. International Journal of Immunopathology and Pharmacology, 20(3), 619-630.