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Intestinal exposure to PCB 153 induces inflammation via the ATM/NEMO pathway
- Source :
- Toxicology and applied pharmacology. 339
- Publication Year :
- 2017
-
Abstract
- Background Polychlorinated biphenyls (PCBs) are persistent organic pollutants that adversely affect human health. PCBs bio-accumulate in organisms important for human consumption. PCBs accumulation in the body leads to activation of the transcription factor NF-κB, a major driver of inflammation. Despite dietary exposure being one of the main routes of exposure to PCBs, the gut has been widely ignored when studying the effects of PCBs. Objectives We investigated the effects of PCB 153 on the intestine and addressed whether PCB 153 affected intestinal permeability or inflammation and the mechanism by which this occurred. Methods Mice were orally exposed to PCB 153 and gut permeability was assessed. Intestinal epithelial cells (IECs) were collected and evaluated for evidence of genotoxicity and inflammation. A human IEC line (SW480) was used to examine the direct effects of PCB 153 on epithelial function. NF-кB activation was measured using a reporter assay, DNA damage was assessed, and cytokine expression was ascertained with real-time PCR. Results Mice orally exposed to PCB 153 had an increase in intestinal permeability and inflammatory cytokine expression in their IECs; inhibition of NF-кB ameliorated both these effects. This inflammation was associated with genotoxic damage and NF-кB activation. Exposure of SW480 cells to PCB 153 led to similar effects as seen in vivo . We found that activation of the ATM/NEMO pathway by genotoxic stress was upstream of NF-kB activation. Conclusions These results demonstrate that oral exposure to PCB 153 is genotoxic to IECs and induces downstream inflammation and barrier dysfunction in the intestinal epithelium.
- Subjects :
- 0301 basic medicine
Male
DNA damage
Inflammation
Genotoxic Stress
Ataxia Telangiectasia Mutated Proteins
Pharmacology
Toxicology
medicine.disease_cause
Article
Cell Line
03 medical and health sciences
chemistry.chemical_compound
Mice
medicine
Animals
Humans
Intestinal Mucosa
Intestinal permeability
Intracellular Signaling Peptides and Proteins
food and beverages
Polychlorinated biphenyl
NF-κB
medicine.disease
Intestinal epithelium
Polychlorinated Biphenyls
Mice, Inbred C57BL
030104 developmental biology
chemistry
medicine.symptom
Inflammation Mediators
Genotoxicity
DNA Damage
Signal Transduction
Subjects
Details
- ISSN :
- 10960333
- Volume :
- 339
- Database :
- OpenAIRE
- Journal :
- Toxicology and applied pharmacology
- Accession number :
- edsair.doi.dedup.....a46158d1dc2378f7f137fd89cac4562a