Tags

Type your tag names separated by a space and hit enter

Luminal cysteine-proteases degrade colonic tight junction structure and are responsible for abdominal pain in constipation-predominant IBS.
Am J Gastroenterol. 2013 Aug; 108(8):1322-31.AJ

Abstract

OBJECTIVES

Luminal serine-proteases lead to increased colonic paracellular permeability and visceral hypersensitivity in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Other proteases, namely cysteine-proteases (CPs), increase airway permeability by digesting epithelial tight junction proteins. In this study, we focused on constipation-predominant IBS (IBS-C) and we aimed to (i) evaluate CP levels in two cohorts of IBS patients, (ii) test if IBS-C fecal supernatant (FSN) affects permeability, and visceral sensitivity after repeated administrations in mice, and (iii) evaluate occludin expression in IBS-C colonic biopsies.

METHODS

Fecal CP activity was determined using selective substrate and inhibitor (E64). The effect of papain, as positive control, and IBS-C FSN administrations were evaluated on colonic paracellular permeability and mucosal occludin levels in mice and T84 monolayers. Occludin protein levels were evaluated in IBS-C colonic biopsies. Sensitivity to colorectal distension (CRD) was measured after repeated administrations of IBS-C FSN.

RESULTS

We found in a subset of IBS-C patients an enhanced fecal CP activity, in comparison with healthy controls and IBS-D patients. CP activity levels positively correlated with disease severity and abdominal pain scoring. This association was confirmed by receiver operating characteristic curve analysis. In mice, repeated application of IBS-C FSN into colon triggered increased permeability, linked to the enzymatic degradation of occludin, and was associated with enhanced visceral sensitivity to CRD. Finally, occludin levels were found decreased in colonic biopsies from IBS-C patients, and IBS-C FSNs were able to degrade recombinant human occludin in vitro. All these effects were abolished by preincubation of IBS-C FSN with a CP inhibitor, E64.

CONCLUSIONS

These data suggest that luminal CPs may represent a new factor contributing to the genesis of symptoms in IBS.

Authors+Show Affiliations

INRA, UMR1331, Neuro-Gastroenterology and Nutrition Group, Toulouse, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23711626

Citation

Annaházi, Anita, et al. "Luminal Cysteine-proteases Degrade Colonic Tight Junction Structure and Are Responsible for Abdominal Pain in Constipation-predominant IBS." The American Journal of Gastroenterology, vol. 108, no. 8, 2013, pp. 1322-31.
Annaházi A, Ferrier L, Bézirard V, et al. Luminal cysteine-proteases degrade colonic tight junction structure and are responsible for abdominal pain in constipation-predominant IBS. Am J Gastroenterol. 2013;108(8):1322-31.
Annaházi, A., Ferrier, L., Bézirard, V., Lévêque, M., Eutamène, H., Ait-Belgnaoui, A., Coëffier, M., Ducrotté, P., Róka, R., Inczefi, O., Gecse, K., Rosztóczy, A., Molnár, T., Ringel-Kulka, T., Ringel, Y., Piche, T., Theodorou, V., Wittmann, T., & Bueno, L. (2013). Luminal cysteine-proteases degrade colonic tight junction structure and are responsible for abdominal pain in constipation-predominant IBS. The American Journal of Gastroenterology, 108(8), 1322-31. https://doi.org/10.1038/ajg.2013.152
Annaházi A, et al. Luminal Cysteine-proteases Degrade Colonic Tight Junction Structure and Are Responsible for Abdominal Pain in Constipation-predominant IBS. Am J Gastroenterol. 2013;108(8):1322-31. PubMed PMID: 23711626.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Luminal cysteine-proteases degrade colonic tight junction structure and are responsible for abdominal pain in constipation-predominant IBS. AU - Annaházi,Anita, AU - Ferrier,Laurent, AU - Bézirard,Valerie, AU - Lévêque,Mathilde, AU - Eutamène,Helene, AU - Ait-Belgnaoui,Afifa, AU - Coëffier,Moïse, AU - Ducrotté,Philippe, AU - Róka,Richárd, AU - Inczefi,Orsolya, AU - Gecse,Krisztina, AU - Rosztóczy,András, AU - Molnár,Tamás, AU - Ringel-Kulka,Tamar, AU - Ringel,Yehuda, AU - Piche,Thierry, AU - Theodorou,Vassilia, AU - Wittmann,Tibor, AU - Bueno,Lionel, Y1 - 2013/05/28/ PY - 2013/01/22/received PY - 2013/04/22/accepted PY - 2013/5/29/entrez PY - 2013/5/29/pubmed PY - 2013/11/1/medline SP - 1322 EP - 31 JF - The American journal of gastroenterology JO - Am J Gastroenterol VL - 108 IS - 8 N2 - OBJECTIVES: Luminal serine-proteases lead to increased colonic paracellular permeability and visceral hypersensitivity in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Other proteases, namely cysteine-proteases (CPs), increase airway permeability by digesting epithelial tight junction proteins. In this study, we focused on constipation-predominant IBS (IBS-C) and we aimed to (i) evaluate CP levels in two cohorts of IBS patients, (ii) test if IBS-C fecal supernatant (FSN) affects permeability, and visceral sensitivity after repeated administrations in mice, and (iii) evaluate occludin expression in IBS-C colonic biopsies. METHODS: Fecal CP activity was determined using selective substrate and inhibitor (E64). The effect of papain, as positive control, and IBS-C FSN administrations were evaluated on colonic paracellular permeability and mucosal occludin levels in mice and T84 monolayers. Occludin protein levels were evaluated in IBS-C colonic biopsies. Sensitivity to colorectal distension (CRD) was measured after repeated administrations of IBS-C FSN. RESULTS: We found in a subset of IBS-C patients an enhanced fecal CP activity, in comparison with healthy controls and IBS-D patients. CP activity levels positively correlated with disease severity and abdominal pain scoring. This association was confirmed by receiver operating characteristic curve analysis. In mice, repeated application of IBS-C FSN into colon triggered increased permeability, linked to the enzymatic degradation of occludin, and was associated with enhanced visceral sensitivity to CRD. Finally, occludin levels were found decreased in colonic biopsies from IBS-C patients, and IBS-C FSNs were able to degrade recombinant human occludin in vitro. All these effects were abolished by preincubation of IBS-C FSN with a CP inhibitor, E64. CONCLUSIONS: These data suggest that luminal CPs may represent a new factor contributing to the genesis of symptoms in IBS. SN - 1572-0241 UR - https://www.unboundmedicine.com/medline/citation/23711626/Luminal_cysteine_proteases_degrade_colonic_tight_junction_structure_and_are_responsible_for_abdominal_pain_in_constipation_predominant_IBS_ DB - PRIME DP - Unbound Medicine ER -