A novel pathway by which the environmental toxin 4-Nonylphenol may promote an inflammatory response in inflammatory bowel disease
Albert Kim, Byeong Ho Jung, Patrick Cadet
Department of Biology, Neuroscience Research Institute, State University of New York – College at Old Westbury, Old Westbury, USA
Med Sci Monit Basic Res 2014; 20:47-54
Available online: 2014-04-10
4-Nonylphenol is a ubiquitous environmental toxin that is formed as a byproduct in the manufacturing and/or sewage treatment of regular household items. Previous work in our lab has implicated 4-NP in the progression of autoimmune diseases such as inflammatory bowel disease in which macrophages mistakenly attack the intestinal linings, causing chronic inflammation. Several key pro-and anti-inflammatory molecules have been shown to be involved in the manifestation of this disease, including IL-23A, COX-2, IL-8, TLR-4, and IL-10.
Material and Methods: 4-NP’s effects on these known mediators of IBD were effectively analyzed using a novel model for IBD, by which 4-NP may promote an inflammatory response. Data were collected using DNA Microarray, RT-PCR, and ELISA, after 48 hour treatment of U937 histiocytic lymphocyte cells and COLO320DM human intestinal epithelial cells with 1 nM and 5 nM concentrations of 4-NP.
Results: Significant dysregulation of the expression of both pro- and anti-inflammatory genes was observed in U937 cells that would promote and prolong inflammation. However, TLR-4, IL-8, and COX-2 gene expressions showed unprecedented effects in COLO320DM cells suggesting that these genes mediate apoptotic processes within the gastrointestinal tract.
Conclusions: Overall, our results suggest that 4-NP administration engenders immune responses linked to apoptotic processes via dysregulation of macrophage signaling. In sum, 4-NP appears to increases the risk of developing inflammatory bowel disease by promoting or prolonging adverse progression of inflammation in the gastrointestinal tract.
Keywords: Environmental Pollutants - toxicity, Cytokines - metabolism, Cell Line, Gene Expression Regulation - drug effects, Inflammation - pathology, Inflammatory Bowel Diseases - pathology, Oligonucleotide Array Sequence Analysis, Phenols - toxicity, RNA, Messenger - metabolism, Reference Standards, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction - genetics