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Bindu Chandrasekharan, Efi Kokkotou, Malu Tansey, Shanthi Srinivasan, P-196 YI TNF-α Inhibitors Attenuate Neuropeptide Y (NPY) Expression in the Murine Enteric Nervous System: Implications in Inflammation and Colonic Motility, Inflammatory Bowel Diseases, Volume 18, Issue suppl_1, 1 December 2012, Page S93, https://doi.org/10.1097/00054725-201212001-00229
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Neuropeptide Y (NPY) is a small peptide neurotransmitter produced by the enteric neurons. We have demonstrated that NPY is upregulated in the murine enteric nervous system (ENS) during experimental colitis and that NPY knockout mice are resistant to experimental colitis. However the mechanism of NPY up regulation in the ENS, and its downstream impact on colonic motility are unknown. We investigated whether TNF-α inhibitor, Etanercept, can regulate NPY expression and colonic motility.
We utilized an enteric neuronal cell line developed in our laboratory and dextran sodium sulfate mouse model of colitis to study NPY expression as modulated by TNF-α. NPY expression in human colonic biopsies was assessed by real time PCR. Colonic motility was assessed in using isometric muscle recording in isolated circular muscle strips with intact innervation. Neuronal apoptosis was evaluated by cleaved caspase-3 immunostaining. Neuronal nitric oxide synthase containing neurons (nNOS) were quantified by Diaphorase staining.
NPY expression was upregulated in human IBD, and IBD colons displayed increased neuronal apoptosis and impaired motility. Etanercept attenuated NPY expression in vitro and in vivo. Etanercept-treated mice exhibited attenuated inflammation and reduction in neuronal apoptosis. There was restoration of nNOS neurons in DSS mice treated with Etanercept, which was evidenced by the reduction in pellet frequency and water content (diarrhea phenotype typical of IBD).
Our data establish the significance of NPY-TNF-α interactions in IBD. Motility disorders persist in IBD patients even after the resolution of inflammation; hence it is compelling to further explore the role of TNF-α inhibitors in modulating motility issues associated with inflammatory disorders.
- apoptosis
- phenotype
- polymerase chain reaction
- tumor necrosis factors
- immunohistochemistry
- inflammation
- inflammatory bowel disease
- diarrhea
- etanercept
- cell lines
- cell motility
- colitis
- enteric nervous system
- dihydrolipoamide dehydrogenase
- mice, knockout
- neurons
- neuropeptide y
- neurotransmitters
- nitric oxide synthase
- peptides
- up-regulation (physiology)
- colon
- mice
- sodium
- irritable bowel syndrome
- motility disorders
- nerve supply
- sulfate
- inflammatory disorders
- dextran
- colon biopsy
- attenuation
- caspase-3
