cyclin-d1 and Pulmonary-Eosinophilia

We have recently reported that antioxidant liposomes can be used as antidotes for mustard gas induced lung injury in guinea pigs. The maximum protection was achieved with a liposome composed of tocopherols (alpha, gamma, delta) and N-acetylcysteine (NAC) when administered after 5 min of exposure of 2-chloroethyl ethyl sulfide (CEES), a half sulfur mustard gas. We also reported an association of mustard gas-induced lung injury with an activation of MAPK/AP-1 signaling pathway and cell proliferation. The objective of the present study was to investigate whether CEES-induced MAPKs/AP-1 signaling pathway is influenced by antioxidant liposome therapy. A single dose (200 microl) of the antioxidant liposome was administered intratracheally after 5 min of exposure of CEES (0.5 mg/kg). The animals were sacrificed after 1h and 30 days of CEES exposure. Although the liposome treatment did not have any significant effect on the activation of the MAPKs family (ERK1/2, p38 and JNK1/2), it significantly counteracted the CEES-induced activation of AP-1 transcription factors and corresponding increase in the protein levels of Fos, ATF and Jun family members. The liposome treatment significantly blocked the CEES-induced increase in the protein levels of cyclin D1, a cell cycle protein and PCNA, a cell differentiation marker. Furthermore, it protected lung against CEES-induced inflammation and infiltration of neutrophils, eosinophils and erythrocytes in the alveolar space. This suggests that the protective effect of antioxidant liposome against CEES-induced lung damage is mediated via control of AP-1 signaling.

Topics: Acetylcysteine; Activating Transcription Factors; Animals; Antidotes; Antioxidants; Blood Proteins; Cell Proliferation; Cyclin D1; Disease Models, Animal; Erythrocytes; Guinea Pigs; Liposomes; Lung; Lung Injury; Male; Mitogen-Activated Protein Kinases; Mustard Gas; Neutrophil Infiltration; Phosphorylation; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Pulmonary Eosinophilia; Time Factors; Tocopherols; Transcription Factor AP-1; Tumor Necrosis Factor-alpha