Signal transduction events in lung injury induced by 2-chloroethyl ethyl sulfide, a mustard analog

✍ Scribed by Diptendu Chatterjee; Shyamali Mukherjee; Milton G. Smith; Salil K. Das

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 215 KB
• Volume: 17
• Category: Article
• ISSN: 1095-6670
• DOI: 10.1002/jbt.10068

✦ Synopsis

Abstract

Sulfur mustard has been used as a vesicant chemical warfare agent. To understand the mechanism by which mustard gas exposure causes respiratory damage, we have used 2‐chloroethyl ethyl sulfide (CEES) as a mustard analog. Our initial studies have shown that guinea pigs exposed to CEES intratracheally accumulate high levels of TNF‐α. Accumulation of TNF‐α leads to activation of both acid and neutral sphingomyelinases, resulting in high accumulation of ceramides, a second messenger involved in cell apoptosis. In addition, NF‐κB was activated for a short period (1–2 h after exposure) as determined by mobility shift assay. Supershift assays indicated that both p50 and p65 of NF‐κB were activated due to CEES exposure. However, NF‐κB rapidly disappeared after 2 h. It is possible that the initial activation of NF‐κB was an adaptive response to protect the cells from damage since NF‐κB is known to inhibit TNF‐α/ceramide‐induced cell apoptosis. Since NF‐κB disappeared after 2 h, the cells continued being damaged owing to accumulation of ceramides and activation of several caspases, leading to apoptosis. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:114–121, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10068