alexa Tumor necrosis factor-neuropeptide Y cross talk regulates inflammation, epithelial barrier functions, and colonic motility.
Oncology

Oncology

Cancer Surgery

Author(s): Chandrasekharan B, Jeppsson S, Pienkowski S, Belsham DD, Sitaraman SV, , Chandrasekharan B, Jeppsson S, Pienkowski S, Belsham DD, Sitaraman SV,

Abstract Share this page

Abstract BACKGROUND: Neuro-immune interactions play a significant role in regulating the severity of inflammation. Our previous work demonstrated that neuropeptide Y (NPY) is upregulated in the enteric nervous system during murine colitis and that NPY knockout mice exhibit reduced inflammation. Here, we investigated if NPY expression during inflammation is induced by tumor necrosis factor (TNF), the main proinflammatory cytokine. METHODS: Using primary enteric neurons and colon explant cultures from wild type and NPY knockout (NPY(-/-)) mice, we determined if NPY knockdown modulates TNF release and epithelial permeability. Further, we assessed if NPY expression is inducible by TNF in enteric neuronal cells and mouse model of experimental colitis, using the TNF inhibitors-etanercept (blocks transmembrane and soluble TNF) and XPro1595 (blocks soluble TNF only). RESULTS: We found that enteric neurons express TNF receptors (TNFR1 and R2). Primary enteric neurons from NPY(-/-) mice produced less TNF compared with wild type. Further, TNF activated NPY promoter in enteric neurons through phospho-c-Jun. NPY(-/-) mice had decreased intestinal permeability. In vitro, NPY increased epithelial permeability through phosphatidyl inositol-3-kinase (PI3-K)-induced pore-forming claudin-2. TNF inhibitors attenuated NPY expression in vitro and in vivo. TNF inhibitor-treated colitic mice exhibited reduced NPY expression and inflammation, reduced oxidative stress, enhanced neuronal survival, and improved colonic motility. XPro1595 had more protective effects on neuronal survival and motility compared with etanercept. CONCLUSIONS: We demonstrate a novel TNF-NPY cross talk that modulates inflammation, barrier functions, and colonic motility during inflammation. It is also suggested that selective blocking of soluble TNF may be a better therapeutic option than using anti-TNF antibodies.
This article was published in Inflamm Bowel Dis and referenced in Cancer Surgery

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords