von der Weid, Pierre-YvesChen, Yingxuan2014-12-222015-02-232014-12-222014http://hdl.handle.net/11023/1968Upregulated TNF-α production and dysfunctional lymphatic pumping are observed in inflammatory bowel disease pathogenesis. It has been previously demonstrated that iNOS is involved in impaired mesenteric lymphatic pumping in animal model of intestinal inflammation and studies showed that TNF-α could decrease arterial contractility via iNOS activation. We hypothesized that TNF-α may induce impaired lymphatic pumping in intestinal inflammation and investigated the effects of TNF-α on rat mesenteric lymphatic pumping and its signaling pathway. Using pressure myography, we showed that the contraction frequency of isolated rat mesenteric lymphatic vessels was significantly decreased after TNF-α treatment, an effect restored following administration of PDTC, 1400W, ODQ or glibenclamide. Upregulation of phospho-IκB in TNF-α-treated vessels was demonstrated by western blot. We also showed upregulation of iNOS mRNA in TNF-α-treated vessels by quantitative real-time PCR and its suppression when PDTC was added. These findings suggest that TNF-α decreases lymphatic contractility via TNF-α- NF-κB- iNOS pathway.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.PhysiologyPathologyPharmacologyTNF-αLymphatic PumpingSignaling PathwayInflammationmaster thesis10.11575/PRISM/28114