Effect of rosiglitazone and 15-deoxy- 12,14-prostaglandin J2 on bleomycin-induced lung injury

Abstract

Thiazolidinedione rosiglitazone and 15-deoxy-D 12,14 -prostaglandin J 2 (15d-PGJ 2 ), are two peroxisome proliferator-activated receptor (PPAR)-c ligands. The aim of this study was to investigate the effect of rosiglitazone and 15d-PGJ 2 on the lung injury caused by bleomycin administration.Mice subjected to intratracheal administration of bleomycin developed significant lung injury. An increase in immunoreactivity to nitrotyrosine, poly(ADP ribose) polymerase (PARP) and inducible nitric oxide synthase as well as a significant loss of body weight and mortality was observed in the lung of bleomycin-treated mice.Administration of the two PPAR-c agonists rosiglitazone (10 mg?kg -1 i.p.) and 15d-PGJ 2 (30 mg?kg -1 i.p.) significantly reduced the: 1) loss of body weight, 2) mortality rate, 3) infiltration of the lung with polymorphonuclear neutrophils (myeloperoxidase activity), 4) oedema formation, and 5) histological evidence of lung injury. Administration of rosiglitazone and 15d-PGJ 2 also markedly reduced the nitrotyrosine, PARP and inducible nitric oxide synthase formation. In addition, treatment with the PPAR-c antagonist bisphenol A diglycidyl ether (1 mg?kg -1 i.p. 30 min before the rosiglitazone or 15d-PGJ 2 ) significantly antagonised the effect of the two PPAR-c agonists.These results demonstrate that the two peroxisome proliferator-activated receptor-c agonists, rosiglitazone and 15-deoxy-D 12,14 -prostaglandin J 2 , significantly reduce lung injury induced by bleomycin in mice.

Two-Way Conversion between Lipogenic and Myogenic Fibroblastic Phenotypes Marks the Progression and Resolution of Lung Fibrosis

“…PPARγ, the master switch of lipogenic differentiation in preadipocytes as well as mesenchymal stem cells, is also involved in lipofibroblast formation (Rehan and Torday, 2012) and PPARγ agonists have been shown to protect mice from developing fibrosis Genovese et al, 2005). Furthermore, adiponectin, which is a direct transcriptional target for PPARγ, has shown a similar effect in primary culture of skin fibroblasts isolated from scleroderma patients .…”

Peroxisome proliferator‐activated receptor‐γ agonists inhibit respiratory syncytial virus‐induced expression of intercellular adhesion molecule‐1 in human lung epithelial cells

“…42,43 Genovese and coworkers reported that neutrophil infiltration of the lung was significantly reduced by PPAR-c agonists in the course of bleomycin-induced mouse lung injury. 44 Also, in a murine in vivo model of LPS-induced airway inflammation it was shown by Birrell and colleagues that the TZD rosiglitazone but not dexamethasone reduced the neutrophil number in the lung tissue when administered after the LPS insult. 45 Interestingly, when we added PPAR-c agonists directly or 12 hr post-RSV-infection we still observed a down-regulation of ICAM-1 on RSV-infected A549 cells similar to the data presented in this study (data not shown).…”

Nrf2-regulated PPARγ Expression Is Critical to Protection against Acute Lung Injury in Mice

“…PPARg ligands also have antifibrogenic potential in murine airways. For example, administration of thiazolidinediones or 15d-PGJ 2 inhibited bleomycin-induced pulmonary injury and fibrosis in mice (33,76). PPARg agonists are postulated to act through cell cycle arrest and TGF-b1 inhibition for myofibroblast differentiation and collagen deposition (76,77).…”

“…The dose was chosen based on previous publications in which PPARg was efficiently induced in the lung (32,33). The last injection was done 24 hours before the end of the designated inhalation exposure period.…”