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- Maiti, Arpan K., et al.
(författare)
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Colonic levels of vasoactive intestinal peptide decrease during infection and exogenous VIP protects epithelial mitochondria against the negative effects of IFN gamma and TNF alpha induced during Citrobacter rodentium infection
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:9
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Tidskriftsartikel (refereegranskat)abstract
- Citrobacter rodentium infection is a model for infection with attaching and effacing pathogens, such as enteropathogenic Escherichia coli. The vasoactive intestinal peptide (VIP) has emerged as an anti-inflammatory agent, documented to inhibit Th1 immune responses and successfully treat animal models of inflammation. VIP is also a mucus secretagogue. Here, we found that colonic levels of VIP decrease during murine C. rodentium infection with a similar time dependency as measurements reflecting mitochondrial function and epithelial integrity. The decrease in VIP appears mainly driven by changes in the cytokine environment, as no changes in VIP levels were detected in infected mice lacking interferon gamma (IFN gamma). VIP supplementation alleviated the reduction of activity and levels of mitochondrial respiratory complexes I and IV, mitochondrial phosphorylation capacity, transmembrane potential and ATP generation caused by IFN gamma, TNF alpha and C. rodentium infection, in an in vitro mucosal surface. Similarly, VIP treatment regimens that included the day 5-10 post infection period alleviated decreases in enzyme complexes I and IV, phosphorylation capacity, mitochondrial transmembrane potential and ATP generation as well as increased apoptosis levels during murine infection with C. rodentium. However, VIP treatment failed to alleviate colitis, although there was a tendency to decreased pathogen density in contact with the epithelium and in the spleen. Both in vivo and in vitro, NO generation increased during C. rodentium infection, which was alleviated by VIP. Thus, therapeutic VIP administration to restore the decreased levels during infection had beneficial effects on epithelial cells and their mitochondria, but not on the overall infection outcome.
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| 2. |
- Su, C., et al.
(författare)
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Influence of the viscosity of healthy and diseased human mucins on the motility of Helicobacter pylori
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- We present particle tracking microrheology results on human mucins, isolated from normal surface and gland mucosa and one tumor sample, and examine the motility of Helicobacter pylori in these mucins. At 1.5% concentration human mucin solutions are purely viscous, with viscosity eta (gland mucin) > eta (surface mucin) > eta (tumor mucin). In the presence of motile H. pylori bacteria, particle diffusion is enhanced, with diffusivity D+bac (tumor mucin) > D+bac (gland mucin) > D+bac(surface mucin). The surface and tumor mucin solutions exhibit an elastic response in the presence of bacteria. Taken together these results imply that particle diffusion and active swimming are coupled and impact the rheology of mucin solutions. Both J99 wild type (WT) and its isogenic Delta babA/Delta sabA mutant swam well in broth or PGM solutions. However, the human mucins affected their motility differently, rendering them immotile in certain instances. The distribution of swimming speeds in human mucin solutions was broader with a large fraction of fast swimmers compared to PGM and broth. The bacteria swam fastest in the tumor mucin solution correlating with it having the lowest viscosity of all mucin solutions. Overall, these results suggest that mucins from different tissue locations and disease status differ in their microrheological properties and their effect on H. pylori motility.
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