Corticotropin-releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro

Wallon, Conny; Yang, Ping‐Chang; Keita, Åsa V.; Ericson, Ann‐Charlott; McKay, Derek M.; Sherman, Philip M.; Perdue, Mary H.; Söderholm, Johan D.

doi:10.1136/gut.2006.117549

Cited by 242 publications

(235 citation statements)

References 53 publications

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“…The severity of psychological stress and the number of mucosal mast cells were found to be correlated in IBS patients regardless of the subtypes [88]. The increased permeability was blocked by the mast cell stabilizer lodoxamide or by disodium cromoglycate pretreatment [89,90], indicating the importance of mediators released from infiltrated mast cells in intestinal permeability.…”

Section: Irritable Bowel Syndrome (Ibs)mentioning

confidence: 83%

Gastrointestinal mucosal barrier function and diseases

2016

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The gastrointestinal mucosal barrier plays an essential role in the separation of the inside of the body from the outside environment. Tight junctions (TJs) are the most important component for construction of a constitutive barrier of epithelial cells, and they regulate the permeability of the barrier by tightly sealing the cell-cell junctions. TJ proteins are represented by claudins, occludin, junctional adhesion molecules, and scaffold protein zonula occludens. Among these TJ proteins, claudins are the major components of TJs and are responsible for the barrier and the polarity of the epithelial cells. Gastrointestinal diseases including reflux esophagitis, inflammatory bowel disease, functional gastrointestinal disorders, and cancers may be regulated by these molecules, and disruption of their functions leads to chronic inflammatory conditions and chronic or progressive disease. Therefore, regulation of the barrier function of epithelial cells by regulating the expression and localization of TJ proteins is a potential new target for the treatment of these diseases. Treatment strategies for these diseases might thus be largely altered if symptom generation and/or immune dysfunction could be regulated through improvement of mucosal barrier function. Since TJ proteins may also modify tumor infiltration and metastasis, other important goals include finding a good TJ biomarker of cancer progression and patient prognosis, and developing TJ protein-targeted therapies that can modify patient prognosis. This review summarizes current understanding of gastrointestinal barrier function, TJ protein expression, and the mechanisms underlying epithelial barrier dysregulation in gastrointestinal diseases.

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Section: Irritable Bowel Syndrome (Ibs)mentioning

confidence: 83%

Gastrointestinal mucosal barrier function and diseases

2016

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“…140,141 Several observations link clinical relapses to the increase in intestinal permeability 142,143 and to life stress, 144,145 partly through mast cell activation 146 and the release of CRF from eosinophils 83 and neighboring nerves. 68 Moreover, inflammatory Public speech and CRF administration increased intestinal permeability and salivary cortisol. Increased permeability after public speech was only present in subjects with a significant elevation of cortisol.…”

Section: Clinical Consequences Of Stress/ Corticotropin-releasing Facmentioning

confidence: 99%

Role of Corticotropin-releasing Factor in Gastrointestinal Permeability

Rodiño-Janeiro¹,

Alonso-Cotoner²,

Pigrau³

et al. 2015

J Neurogastroenterol Motil

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The interface between the intestinal lumen and the mucosa is the location where the majority of ingested immunogenic particles face the scrutiny of the vast gastrointestinal immune system. Upon regular physiological conditions, the intestinal microflora and the epithelial barrier are well prepared to process daily a huge amount of food-derived antigens and non-immunogenic particles. Similarly, they are ready to prevent environmental toxins and microbial antigens to penetrate further and interact with the mucosal-associated immune system. These functions promote the development of proper immune responses and oral tolerance and prevent disease and inflammation. Brain-gut axis structures participate in the processing and execution of response signals to external and internal stimuli. The brain-gut axis integrates local and distant regulatory networks and supersystems that serve key housekeeping physiological functions including the balanced functioning of the intestinal barrier. Disturbance of the brain-gut axis may induce intestinal barrier dysfunction, increasing the risk of uncontrolled immunological reactions, which may indeed trigger transient mucosal inflammation and gut disease. There is a large body of evidence indicating that stress, through the brain-gut axis, may cause intestinal barrier dysfunction, mainly via the systemic and peripheral release of corticotropin-releasing factor. In this review, we describe the role of stress and corticotropin-releasing factor in the regulation of gastrointestinal permeability, and discuss the link to both health and pathological conditions. (J Neurogastroenterol Motil 2015;21:33-50)

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“…62,84 Plenty of work has been done to verify the concept that MCs contribute to stress induced gut dysfunction. For example, MCs mediate stress induced intestinal barrier disruption [85][86][87] and visceral hypersensitivity 82,88,89 due to the release of tryptase, TNF-α, 86 and histamine. 82 Peripheral administration of H 1 R antagonists fexofenadine and ebastine are capable of reversing post stress visceral hypersensitivity in rats.…”

Section: Central Stress: Psychological Distress and Negative Life Eventsmentioning

confidence: 99%

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Zhang

Song

Hou

2016

J Neurogastroenterol Motil

111

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Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder since it lacks demonstrable pathological abnormalities. However, in recent years, low grade inflammatory infiltration, often rich in mast cells, in both the small and large bowel, has been observed in some patients with IBS. The close association of mast cells with major intestinal functions, such as epithelial secretion and permeability, neuroimmune interactions, visceral sensation, and peristalsis, makes researchers and gastroenterologists to focus attention on the key roles of mast cells in the pathogenesis of IBS. Numerous studies have been carried out to identify the mechanisms in the development, infiltration, activation, and degranulation of intestinal mast cells, as well as the actions of mast cells in the processes of mucosal barrier disruption, mucosal immune dysregulation, visceral hypersensitivity, dysmotility, and local and central stress in IBS. Moreover, therapies targeting mast cells, such as mast cell stabilizers (cromoglycate and ketotifen) and antagonists of histamine and serotonin receptors, have been tried in IBS patients, and have partially exhibited considerable efficacy. This review focuses on recent advances in the role of mast cells in IBS, with particular emphasis on bridging experimental data with clinical therapeutics for IBS patients.

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Corticotropin-releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro

Abstract: Our results suggest that CRH mediates transcellular uptake of HRP in human colonic mucosa via CRH receptor subtypes R1 and R2 on subepithelial mast cells. CRH-induced macromolecular uptake in human colon mucosa may have implications for stress-related intestinal disorders.

Cited by 242 publications

References 53 publications

Gastrointestinal mucosal barrier function and diseases

Gastrointestinal mucosal barrier function and diseases

Role of Corticotropin-releasing Factor in Gastrointestinal Permeability

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

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