Gulf War agents trigger discrete transcriptional changes in human neuronal cells

Abstract

Reports on Gulf War illness (GWI) implicated the use of the pesticide permethrin (PER), and the insect repellent N,N-diethyl-m-toluamide (DEET), in its etiology, as well as pyridostigmine bromide (PB), which was given as a prophylactic treatment against nerve agent exposure. Using Affymetrix microarrays the genomic response of human neuronal SHSY-5Y cells to 10 days of exposure to these agents was characterized and profiles of gene modulation unique to each treatment were demonstrated. In particular, a significantly greater impact of PER was observed compared to the other treatments. The Ingenuity Pathway Analysis knowledgebase was used to analyze the genomic datasets and attribute functional consequences to the effects of related genes, which were significantly up- or down-regulated in response to different treatments. Canonical pathways shown to be significantly modulated at the genomic level in response to exposure included cellular mechanisms, which might contribute to the clinical presentation in GWI patients and thus be targeted for further investigation as potential targets for therapeutic intervention.

Keywords:

• Gulf War illness
• permethrin
• DEET
• pyridostigmine bromide

Acknowledgment

This work was supported by a VA Merit award to F. Crawford and M. Mullan and by the Roskamp Foundation.