TY - JOUR
T1 - Glycogen synthase kinase-3β inhibition attenuates the development of bleomycin-induced lung injury
AU - Cuzzocrea, Salvatore
AU - Genovese, T.
AU - Mazzon, E.
AU - Esposito, E.
AU - Muià, C.
AU - Abdelrahman, M.
AU - Di Paola, R.
AU - Bramanti, P.
AU - Thiemermann, C.
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
KW - Bleomycin
KW - Cytokines
KW - Glycogen synthase kinase-3 (GSK-3)
KW - Inflammation
KW - Neutrophil infiltration
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=34948896426&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34948896426&partnerID=8YFLogxK
M3 - Article
C2 - 17880775
AN - SCOPUS:34948896426
VL - 20
SP - 619
EP - 630
JO - International Journal of Immunopathology and Pharmacology
JF - International Journal of Immunopathology and Pharmacology
SN - 0394-6320
IS - 3
ER -