Non-immune cells from a variety of organs, including the liver, lung and skin, when targeted by toxic agents, secrete pro-inflammatory cytokines and chemokines which participate in pathological as well as repair processes. In particular, tumor necrosis factor alpha (TNF a) and certain members of the neutrophil chemoattractant family of chemokines (CXC), including interleukin-8, play major roles in these responses. This presentation will describe several organ model systems for toxicity including asbestor-induced lung disease, arsenic-induced skin toxicity and heavy metal-medicated hepatotoxicity which demonstrate cytokine participation. In addition to describing the nature of these responses, the molecular events responsible will be detailed. A common pathway responsible for cytokine induction in all of these systems involves chemical-medicated, cellular oxidative stress, which, in turn, activates nuclear transcription factors, such as NF-kB, NF-IL-6 and AP-1. Unraveling the complex mechanism associated with these events may provide novel opportunities for intervention.
The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana