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  • 1. Labus, J. S.
    et al.
    Mayer, E. A.
    Jarcho, J.
    Kilpatrick, L. A.
    Kilkens, T. O. C.
    Evers, E. A. T.
    Backes, W. H.
    Brummer, Robert Jan
    Örebro universitet, Hälsoakademin.
    van Nieuwenhoven, Michiel A
    Acute tryptophan depletion alters the effective connectivity of emotional arousal circuitry during visceral stimuli in healthy women2011Inngår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 60, nr 9, s. 1196-1203Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Alterations in serotonin signalling within the brain-gut axis have been implicated in the pathophysiology of irritable bowel syndrome (IBS) and is a treatment target. Acute tryptophan depletion (ATD) decreases brain serotonin (5-hydroxytryptamine; 5-HT) levels, and increases visceral perception and negative emotional bias in patients with IBS. The aim of the present study was to determine the effect of ATD on brain activity and connectivity during visceral stimuli in healthy women, and to compare the ATD-induced brain connectivity of an arousal circuit in female patients with IBS without ATD.

    METHODS: 12 healthy females (19-25 years) were studied under placebo (PLA) conditions and ATD. Functional MRI measurements were performed during a rectal barostat protocol, consisting of random non-painful and maximal tolerable distensions. Partial least squares analyses and structural equation modelling were used to evaluate the effect of ATD on functional and effective brain connectivity during distension. Results in healthy controls under ATD were compared with the effective connectivity of brain responses to 45 mm Hg rectal distension in 14 female patients with constipation-predominant IBS (IBS-C) (24-50 years).

    RESULTS: In healthy controls, ATD resulted in increased response of an extensive brain network to balloon distension, including the amygdala and nodes of emotional arousal and homeostatic afferent networks. The effect was greater during high inflation, suggesting greater engagement of the central serotonion system with more aversive visceral stimuli. Effective connectivity analysis revealed a profound effect of ATD on coupling between emotional arousal network nodes, resulting in loss of negative feedback inhibition of the amygdala. A near-identical pattern was identified in the patients with IBS-C.

    CONCLUSIONS: The findings are consistent with an ATD-induced disinhibition of and increased connectivity within an emotional arousal network during aversive stimulation. Together with the previous demonstration of ATD-induced visceral hyperalgesia in healthy controls, and the near-identical effective connectivity pattern observed in patients with IBS-C, these findings suggest that dysregulation of this brain network may play a role in central pain amplification and IBS pathophysiology.

  • 2.
    Rossi, Oriana
    et al.
    Host-Microbe Interactomics Group, ASG, University of Wageningen, Wageningen, The Netherlands.
    Karczewski, Jurgen
    Host-Microbe Interactomics Group, ASG, University of Wageningen, Wageningen, The Netherlands.
    Stolte, Ellen H
    Host-Microbe Interactomics Group, ASG, University of Wageningen, Wageningen, The Netherlands.
    Brummer, Robert J M
    Örebro universitet, Institutionen för läkarutbildning.
    van Nieuwenhoven, Michiel A
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Meijerink, Marjolein
    Host-Microbe Interactomics Group, ASG, University of Wageningen, Wageningen, The Netherlands .
    van Neerven, Joost R J
    FrieslandCampina, Amersfoort, The Netherlands .
    van Ijzendoorn, Sven C D
    Department of Cell Biology, Section Membrane Cell Biology, University Medical Center Groningen, Groningen, The Netherlands .
    van Baarlen, Peter
    Host-Microbe Interactomics Group, ASG, University of Wageningen, Wageningen, The Netherlands .
    Wells, Jerry M
    Host-Microbe Interactomics Group, ASG, University of Wageningen, Wageningen, The Netherlands .
    Vectorial secretion of interleukin-8 mediates autocrine signalling in intestinal epithelial cells via apically located CXCR12013Inngår i: BMC research notes, ISSN 1756-0500, Vol. 6, s. 431-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: In the intestinal mucosa, several adaptations of TLR signalling have evolved to avoid chronic inflammatory responses to the presence of commensal microbes. Here we investigated whether polarized monolayers of intestinal epithelial cells might regulate inflammatory responses by secreting IL-8 in a vectorial fashion (i.e. apical versus basolateral) depending on the location of the TLR stimulus.

    RESULTS: In the Caco-2 BBE model of polarized villus-like epithelium, apical stimulation with TLR2 and TLR5 ligands resulted in the apical secretion of IL-8. The CXCR1 receptor for IL-8 was expressed only on the apical membrane of Caco-2 BBE cells and differentiated epithelial cells in the human small intestine and colon. Transcriptome analyses revealed that Caco-2 BBE cells respond to stimulation with IL-8 supporting the hypothesis that IL-8 induces G protein-coupled receptor signalling.

    CONCLUSIONS: These results show that IL-8 induces autocrine signalling via an apical CXCR1 in Caco-2 BBE intestinal epithelial cells and that this receptor is also expressed on the apical surface of differentiated human intestinal epithelial cells in vivo, suggesting an autocrine function for IL-8 secreted in the lumen.

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