Antioxidant liposomes protect against CEES-induced lung injury by decreasing SAF-1/MAZ-mediated inflammation in the guinea pig lung
✍ Scribed by Sutapa Mukhopadhyay; Shyamali Mukherjee; Bimal K. Ray; Alpana Ray; William L. Stone; Salil K. Das
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 321 KB
- Volume
- 24
- Category
- Article
- ISSN
- 1095-6670
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✦ Synopsis
Abstract
We reported earlier in a guinea pig model that exposure of 2‐chloroethyl ethyl sulfide (CEES), a mustard gas analog, causes lung injury associated with the activation of tumor necrosis factor alpha (TNF‐α), mitogen activated protein kinases (MAPK) signaling, and activator protein‐1 (AP‐1) transcription factor. Our earlier studies also revealed that antioxidant liposomes can be used as antidotes. Proinflammatory cytokines IL‐1, IL‐6, and TNF‐α, either alone or in combination, can induce the activation of another group of transcription factors, namely SAF‐1 (serum accelerator factor‐1)/MAZ (Myc‐associated zinc finger protein). Phosphorylation of SAF‐1 via MAPK markedly increases its DNA‐binding and transactivational potential. The objective of the present study was to investigate whether CEES exposure causes activation of IL‐1β, IL‐6, and SAF‐1/MAZ and whether these effects can be prevented by antioxidant liposomes. A single dose (200 μL) of the antioxidant liposome mixture was administered intratracheally after 5 min of exposure of CEES (0.5 mg/kg). The animals were sacrificed either 1 h or 30 days after CEES exposure. CEES exposure caused an upregulation of proinflammatory cytokines IL‐6 and IL‐1β in the lung along with an increase in the activation of transcription factor SAF‐1/MAZ. The antioxidant liposomes treatment significantly blocked the CEES‐induced activation of IL‐6, IL‐1β, and SAF‐1/MAZ. This might suggest that antioxidant liposomes might offer a potential therapeutic strategy against inflammatory diseases associated with activation of these bioactive molecules. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:187–194, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20329