Upregulation of intestinal mucosal mast cells expressing VPAC1 in close proximity to vasoactive intestinal polypeptide in inflammatory bowel disease and murine colitis

Casado‐Bedmar, Maite; Heil, Stéphanie D S; Myrelid, Pär; Söderholm, Johan D.; Keita, Åsa V.

doi:10.1111/nmo.13503

Cited by 30 publications

(20 citation statements)

References 48 publications

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“…VIP is a neurotransmitter produced by different cells, including MC, although mainly derived from neurons, and is also released duringin response to stress [112], particularly chronic, psychological stress. Our group has previously demonstrated pro-inflammatory effects of VIP both in animals and humans [34,112], in line with the observations made herein that showed tightening of mucosal barrier after blocking VIP both in a physiological health situation and a disorder of brain-gut axis strongly associated with chronic stress. We observed increased VIP serum levels and numerically but not statistically higher concentrations of VIP in biopsy lysates in IBS.…”

Section: Brain-gut Axis: Gut Aspectssupporting

confidence: 89%

“…Nevertheless, evidence on the impact of VIP on intestinal barrier is divergent, demonstrating both stabilizing and disrupting effect on gut mucosa. The effect of VIP may plausibly vary depending on different ongoing pathological processes [34]. In fact, both VIP agonists and antagonists have been suggested as promising anti-inflammatory agents in different inflammatory diseases, such as rheumatoid arthritis (VIP agonists) or inflammatory bowel diseases (both VIP agonists and antagonists) [34].…”

Section: Vasoactive Intestinal Polypeptidementioning

confidence: 99%

“…The effect of VIP may plausibly vary depending on different ongoing pathological processes [34]. In fact, both VIP agonists and antagonists have been suggested as promising anti-inflammatory agents in different inflammatory diseases, such as rheumatoid arthritis (VIP agonists) or inflammatory bowel diseases (both VIP agonists and antagonists) [34]. In IBS, increased amount of VIP was detected in colonic biopsies in smaller studies [179,216], however data seem to be inconsistent [196].…”

Section: Vasoactive Intestinal Polypeptidementioning

confidence: 99%

“…As neurotransmitter concentrations alter with age [207], meticulous age-matching was performed with an age range of ± 3 years. From the patients' cohort, 32 women accomplished both sigmoidoscopy and fMRI, while 34 Figure 6. Overview of inclusion process for both IBS patients (A) and healthy controls, HC (B).…”

Section: Specific Aimsmentioning

confidence: 99%

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Peripheral and Central Mechanisms in Irritable Bowel Syndrome : in search of links

Bednarska

2019

Linköping University Medical Dissertations

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Irritable bowel syndrome (IBS) is a chronic visceral pain disorder with female predominance, characterized by recurrent abdominal pain and disturbed bowel habits in the absence of an identifiable organic cause. This prevalent and debilitating disease, which accounts for a substantial economic and individual burden, lacks exact diagnostic tools and effective treatment, since its pathophysiology remains uncertain. The bidirectional and multilayered brain-gut axis is a well-established disease model, however, the interactions between central and peripheral mechanisms along the brain-gut axis remain incompletely understood. One of the welldescribed triggering factors, yet accounting for only a fraction of IBS prevalence, is bacterial gastroenteritis that affects mucosal barrier function. Altered gut microbiota composition as well as disturbed intestinal mucosal barrier function and its neuroimmune regulation have been reported in IBS, however, the impact of live bacteria, neither commensal nor pathogenic, on intestinal barrier has not been studied yet. Furthermore, abnormal central processing of visceral sensations and psychological factors such as maladaptive coping have previously been suggested as centrally-mediated pathophysiological mechanisms of importance in IBS. Brain imaging studies have demonstrated an imbalance in descending pain modulatory networks and alterations in brain regions associated with interoceptive awareness and pain processing and modulation, particularly in anterior insula (aINS), although biochemical changes putatively underlying these central alterations remain poorly understood. Most importantly, however, possible associations between these documented changes on central and peripheral levels, which may as complex interactions contribute to disease onset and chronification of symptoms, are widely unknown. VMpo ventromedial thalamic nucleus posterior portion VPAC vasoactive intestinal polypeptide receptor VSI Visceral Sensitivity Index Recurrent abdominal pain or discomfort** at least 3 days per month in the last 3 months associated with 2 or more of the following: 1. Improvement with defecation 2. Onset associated with a change in frequency of stool 3. Onset associated with a change in form (appearance) of stool *Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis. **Discomfort means an uncomfortable sensation not described as pain. In pathophysiology research and clinical trials, a pain/discomfort frequency of at least 2 days a week during screening evaluation for subject eligibility.

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Section: Brain-gut Axis: Gut Aspectssupporting

confidence: 89%

Section: Vasoactive Intestinal Polypeptidementioning

confidence: 99%

Section: Vasoactive Intestinal Polypeptidementioning

confidence: 99%

Section: Specific Aimsmentioning

confidence: 99%

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Peripheral and Central Mechanisms in Irritable Bowel Syndrome : in search of links

Bednarska

2019

Linköping University Medical Dissertations

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“…The more rapid weight loss observed in the mMCP-4-deficient mice could depend on several chymase-dependent issues. For example, chymase has been shown to degrade the neuropeptide vasoactive intestinal polypeptide (VIP) [63] and VIP regulates intestinal motility [64]. We may speculate that the lack of chymase potentially leads to higher levels of VIP, an increase in intestinal motility, and earlier weight loss in the infected mMCP-4 −/− mice.…”

Section: Discussionmentioning

confidence: 99%

The Chymase Mouse Mast Cell Protease-4 Regulates Intestinal Cytokine Expression in Mature Adult Mice Infected with Giardia intestinalis

Peirasmaki

Svärd

et al. 2020

Cells

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Mast cells have been shown to affect the control of infections with the protozoan parasite Giardia intestinalis. Recently, we demonstrated that Giardia excretory-secretory proteins inhibited the activity of the connective tissue mast cell-specific protease chymase. To study the potential role of the chymase mouse mast cell protease (mMCP)-4 during infections with Giardia, mMCP-4 +/+ and mMCP-4 −/− littermate mice were gavage-infected with G. intestinalis trophozoites of the human assemblage B isolate GS. No significant changes in weight gain was observed in infected young (≈10 weeks old) mMCP-4 −/− and mMCP-4 +/+ littermate mice. In contrast, infections of mature adult mice (>18 weeks old) caused significant weight loss as compared to uninfected control mice. We detected a more rapid weight loss in mMCP-4 −/− mice as compared to littermate mMCP-4 +/+ mice. Submucosal mast cell and granulocyte counts in jejunum increased in the infected adult mMCP-4 −/− and mMCP-4 +/+ mice. This increase was correlated with an augmented intestinal trypsin-like and chymotrypsin-like activity, but the myeloperoxidase activity was constant. Infected mice showed a significantly lower intestinal neutrophil elastase (NE) activity, and in vitro, soluble Giardia proteins inhibited human recombinant NE. Serum levels of IL-6 were significantly increased eight and 13 days post infection (dpi), while intestinal IL-6 levels showed a trend to significant increase 8 dpi. Strikingly, the lack of mMCP-4 resulted in significantly less intestinal transcriptional upregulation of IL-6, TNF-α, IL-25, CXCL2, IL-2, IL-4, IL-5, and IL-10 in the Giardia-infected mature adult mice, suggesting that chymase may play a regulatory role in intestinal cytokine responses.Cells 2020, 9, 925 2 of 19 infections, including infections with G. intestinalis [9][10][11]. However, there is little insight into how Giardia spp. cause disease; they are not invasive and secrete no known toxins [12]. Recent research suggests that G. intestinalis can secrete a large number of immunomodulatory proteins, possibly regulating host immune responses [13][14][15][16]. However, the mechanisms on how interactions between the host and Giardia either lead to parasite clearance or to disease remain to be understood.Recent studies have shown the importance of different immune cells in giardiasis, where both innate and adaptive immunity seem to play significant roles [17][18][19]. Accumulated data suggest that there is a mixed Th1/Th2/Th17 response during giardiasis [19,20]. When G. intestinalis attach to the microvillus brush border of intestinal epithelial cells (IECs) there is a production of chemokines and cytokines that will attract immune cells to the intestinal submucosa [20][21][22]. However, the effects differ depending on model systems used. In cultured human IECs challenged by G. intestinalis trophozoites (assemblage B, isolate GS), several chemokines were highly up-regulated early-at 1.5 h after challenge [21]. In experimental infections of gerbils with the WB isolate (ATCC 50803)...

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Vasoactive Intestinal Peptide (VIP)

Rosa

2022

Encyclopedia of Pathology

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Upregulation of intestinal mucosal mast cells expressing VPAC1 in close proximity to vasoactive intestinal polypeptide in inflammatory bowel disease and murine colitis

Cited by 30 publications

References 48 publications

Peripheral and Central Mechanisms in Irritable Bowel Syndrome : in search of links

Peripheral and Central Mechanisms in Irritable Bowel Syndrome : in search of links

The Chymase Mouse Mast Cell Protease-4 Regulates Intestinal Cytokine Expression in Mature Adult Mice Infected with Giardia intestinalis

Vasoactive Intestinal Peptide (VIP)

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