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Identification of an epithelial member of the protease family, supporting the potential diagnostic and therapeutic role of serine proteases in IBS
  1. Benedicte Y De Winter
  1. Correspondence to Professor Dr Benedicte Y De Winter, Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Universiteitsplein 1, Antwerp 2610, Belgium; benedicte.dewinter{at}uantwerpen.be

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The quest for appropriate diagnostic tools and therapies for IBS runs in parallel with the different pathogenic mechanisms investigated. One of these mechanisms is visceral hypersensitivity, resulting from a disturbed neuronal signalling at the peripheral and/or central levels.1 ,2 Rolland-Fourcade et al3 show, in this issue of Gut, that intestinal epithelial cells (Caco-2 cells) release a trypsin-like activity at the basolateral side of the cells after stimulation with a classical inflammatory stimulus (lipopolysaccharide) or with a stress-related stimulus (epinephrine), and they identified it as trypsin-3. They confirmed the clinical relevance of trypsin-3 by proving its presence in colonic tissue from patients with IBS (all subgroups). Besides, trypsin-3 increased epithelial permeability in the Caco-2 monolayers and increased the excitability of mouse dorsal root ganglia neurons in vitro. Moreover, it induced Ca+2 transients in human submucosal neurons in vitro and caused visceral hyperalgesia in response to colorectal distension in two rat models of visceral hypersensitivity.3 The novelty of this manuscript lies within the identification of a specific protease, namely trypsin-3 and its source, the intestinal epithelium, providing additional evidence for serine proteases and protease-activated receptors (PAR).

The importance of visceral hypersensitivity as a key contributor to the generation of symptoms in patients with …

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