Increased faecal serine protease activity in diarrhoeic IBS patients: a colonic lumenal factor impairing colonic permeability and sensitivity

Gecse, Krisztina; Róka, R; Ferrier, Laurent; Lévêque, Mathilde; Eutamène, Hélène; Cartier, Christel; Ait-Belgnaoui, Afifa; Rosztóczy, A; Izbéki, Ferenc; Fioramonti, Jean; Wittmann, Tibor; Buéno, Lionel

doi:10.1136/gut.2007.140210

Cited by 277 publications

(281 citation statements)

References 36 publications

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“…35 Alterations in the production of these pro-inflammatory cytokines (primarily produced by monocytes and macrophages) are suggestive of an increase in innate immune activity in IBS patients. Accordingly, data collected from D-IBS patients indicate an increase in protease activity in the stool 39 and jejunal fluid 40 and an increase in NO release in the rectal mucosa, 41 indicating the potential involvement of mast cells in the increased release of inflammatory mediators. This finding is consistent with data indicating an increase in blood levels of lipid inflammatory mediators such as prostaglandin E2 and leukotriene B4, which are known to be released from newly formed mast cells.…”

Section: Resultsmentioning

confidence: 99%

“…Two studies have reported a correlation between mast cell density and increased intestinal permeability in IBS patients. 39,71 Finally, several studies have correlated mast cell number with the severity of abdominal pain symptoms, 64,68,73,116 especially when mast cells were found close to enteric nerves. 68,73 Further investigation is required to determine the activation state of mast cells (e.g.…”

Section: Immune Activation In Ibs Patientsmentioning

confidence: 99%

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Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

Matricon

Méleine

Gelot

et al. 2012

Aliment Pharmacol Ther

187

180

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This uncommissioned review article was subject to full peer-review. SUMMARY BackgroundIrritable bowel syndrome (IBS), one of the most common gastrointestinal disorders, markedly impairing patients' quality of life. Drug development for IBS treatment has been hampered by the lack of understanding of IBS aetiology. In recent years, numerous data have emerged that suggest the involvement of immune activation in IBS, at least in a subset of patients. AimTo determine whether immune activation and intestinal permeabilisation are more frequently observed in IBS patients compared with healthy controls. MethodsThe scientific bibliography was searched using the following keywords: irritable bowel syndrome, inflammation, immune activation, permeabilisation, intestine, assay, histology and human. The retrieved studies, including blood, faecal and histological studies, were analysed to provide a comprehensive and structured overview of the available data including the type of assay, type of inflammatory marker investigated or intestinal segment studied. ResultsImmune activation was more frequently observed in IBS patients than in healthy controls. An increase in the number of mast cells and lymphocytes, an alteration in cytokine levels and intestinal permeabilisation were reported in IBS patients. No consistent changes in the numbers of B cells or enterochromaffin cells or in mucosal serotonin production were demonstrated. ConclusionsThe changes observed were modest and often heterogeneous among the studied population. Only appropriate interventions improving irritable bowel syndrome symptoms could highlight and confirm the role of immune activation in this pathophysiology.

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Section: Resultsmentioning

confidence: 99%

Section: Immune Activation In Ibs Patientsmentioning

confidence: 99%

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

Matricon

Méleine

Gelot

et al. 2012

Aliment Pharmacol Ther

187

180

View full text Add to dashboard Cite

show abstract

“…Serine proteases become neurologically active at high levels, producing abdominal aches, muscular contractions and widespread pain. These high levels of serine proteases are not found in viral or bacterial enteritis (Gecse et al 2008). Proteases are produced by protozoa to degrade host immunological factors, such as IgA (Puthia et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Blastocystis subtypes in irritable bowel syndrome and inflammatory bowel disease in Ankara, Turkey

Doğruman-Al

Kuştımur

Yoshikawa

et al. 2009

Mem. Inst. Oswaldo Cruz

118

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“…In particular, the specific contribution of extracellular serine proteases and their cognate inhibitors to epithelial tight junction formation, maintenance, and regulation of barrier function is unclear. [3][4][5][6]20,21 Matriptase is a trypsin-like transmembrane serine protease encoded by the ST14 gene that belongs to the recently emerged type II transmembrane serine protease family. Orthologs of matriptase have been found in all vertebrate species analyzed to date, and homologs of the type II transmembrane serine proteases are present in bees and fruit flies.…”

mentioning

confidence: 99%

Epithelial Integrity Is Maintained by a Matriptase-Dependent Proteolytic Pathway

List

Kósa

Szabo

et al. 2009

The American Journal of Pathology

133

157

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A pericellular proteolytic pathway initiated by the transmembrane serine protease matriptase plays a critical role in the terminal differentiation of epidermal tissues. Matriptase is constitutively expressed in multiple other epithelia, suggesting a putative role of this membrane serine protease in general epithelial homeostasis. Here we generated mice with conditional deletion of the St14 gene, encoding matriptase, and show that matriptase indeed is essential for the maintenance of multiple types of epithelia in the mouse. Thus, embryonic or postnatal ablation of St14 in epithelial tissues of diverse origin and function caused severe organ dysfunction, which was often associated with increased permeability, loss of tight junction function, mislocation of tight junction-associated proteins, and generalized epithelial demise. The study reveals that the homeostasis of multiple simple and stratified epithelia is matriptase-dependent, and provides an important animal model for the exploration of this membrane serine protease in a range of physiological and pathological processes.

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Increased faecal serine protease activity in diarrhoeic IBS patients: a colonic lumenal factor impairing colonic permeability and sensitivity

Abstract: Elevated colonic lumenal serine protease activity of IBS-D patients evokes a PAR-2-mediated colonic epithelial barrier dysfunction and subsequent allodynia in mice, suggesting a novel organic background in the pathogenesis of IBS.

Cited by 277 publications

References 36 publications

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

Blastocystis subtypes in irritable bowel syndrome and inflammatory bowel disease in Ankara, Turkey

Epithelial Integrity Is Maintained by a Matriptase-Dependent Proteolytic Pathway

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