Visceral hypersensitivity in inflammatory bowel diseases and irritable bowel syndrome: The role of proteases

• Published in: World journal of gastroenterology : WJG 2016-12, Vol.22 (47), p.10275-10286
• Main Authors: Ceuleers, Hannah, Van Spaendonk, Hanne, Hanning, Nikita, Heirbaut, Jelena, Lambeir, Anne-Marie, Joossens, Jurgen, Augustyns, Koen, De Man, Joris G, De Meester, Ingrid, De Winter, Benedicte Y
• Format: Article
• Language: English
• Subjects: Abdominal Pain - drug therapy; Abdominal Pain - enzymology; Abdominal Pain - etiology; Abdominal Pain - physiopathology; Animals; Humans; Hyperalgesia - drug therapy; Hyperalgesia - enzymology; Hyperalgesia - etiology; Hyperalgesia - physiopathology; Inflammatory Bowel Diseases - complications; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - enzymology; Inflammatory Bowel Diseases - physiopathology; Intestinal Absorption; Intestines - enzymology; Intestines - innervation; Irritable Bowel Syndrome - complications; Irritable Bowel Syndrome - drug therapy; Irritable Bowel Syndrome - enzymology; Irritable Bowel Syndrome - physiopathology; Peptide Hydrolases - metabolism; Permeability; Protease Inhibitors - therapeutic use; Receptors, Proteinase-Activated - metabolism; Review; Signal Transduction
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v22.i47.10275

Proteases, enzymes catalyzing the hydrolysis of peptide bonds, are present at high concentrations in the gastrointestinal tract. Besides their well-known role in the digestive process, they also function as signaling molecules through the activation of protease-activated receptors(PARs). Based on their chemical mechanism for catalysis, proteases can be classified into several classes: serine, cysteine, aspartic, metallo- and threonine proteases represent the mammalian protease families. In particular, the class of serine proteases will play a significant role in this review. In the last decades, proteases have been suggested to play a key role in the pathogenesis of visceral hypersensitivity, which is a major factor contributing to abdominal pain in patients with inflammatory bowel diseases and/or irritable bowel syndrome. So far, only a few preclinical animal studies have investigated the effect of protease inhibitors specifically on visceral sensitivity while their effect on inflammation is described in more detail. In our accompanying review we describe their effect on gastrointestinal permeability. On account of their promising results in the field of visceral hypersensitivity, further research is warranted. The aim of this review is to give an overview on the concept of visceral hypersensitivity as well as on the physiological and pathophysiological functions of proteases herein.