A novel pathway by which the environmental toxin 4-Nonylphenol may promote an inflammatory response in inflammatory bowel disease.
Background 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.
Department of Biology, Neuroscience Research Institute, State University of New York - College at Old Westbury, Old Westbury, USA.
Albert
A
Kim
Department of Biology, Neuroscience Research Institute, State University of New York - College at Old Westbury, Old Westbury, USA.
Byeong Ho
BH
Jung
Department of Biology, Neuroscience Research Institute, State University of New York - College at Old Westbury, Old Westbury, USA.
Patrick
P
Cadet
D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010636:Phenols / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012015:Reference Standards; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
D016207:Cytokines; D004785:Environmental Pollutants; D010636:Phenols; D012333:RNA, Messenger; C041594:4-nonylphenol