A pilot study of fecal serine-protease activity: a pathophysiologic factor in diarrhea-predominant irritable bowel syndrome.

Background & Aims: The pathogenesis of irritable bowel syndrome (IBS) remains only partially understood, and no specific or universally effective patient management procedure has been developed to date. Our study was designed to evaluate if colonic luminal serine-proteases may be a relevant pathophysiologic marker of IBS.

Methods: Fecal samples of 38 IBS patients, 15 patients with ulcerative colitis (UC), and 15 healthy controls were studied.

PAR2 activation alters colonic paracellular permeability in mice via IFN-gamma-dependent and -independent pathways.

Activation of colonic proteinase-activated receptor-2 (PAR(2)) caused inflammation and increased mucosal permeability in mouse colon. The present study was aimed at characterizing the possible links between these two phenomena. We evaluated the effects of intracolonic infusion of PAR(2)-activating peptide, SLIGRL, on colonic paracellular permeability and inflammation at two different doses, 5 and 100 microg per mouse, in an attempt to discriminate between both PAR(2)-mediated effects.

Colitis induced by proteinase-activated receptor-2 agonists is mediated by a neurogenic mechanism.

Proteinase-activated receptor-2 (PAR2) activation induces colonic inflammation by an unknown mechanism. We hypothesized that PAR2 agonists administered intracolonically in mice induce inflammation via a neurogenic mechanism. Pretreatment of mice with neurokinin-1 and calcitonin-gene-related peptide (CGRP) receptor antagonists or with capsaicin showed attenuated PAR2-agonist-induced colitis.

Stress-induced disruption of colonic epithelial barrier: role of interferon-gamma and myosin light chain kinase in mice.

Background & Aims: Stressful life events are supposed to be involved in various diseases such as inflammatory bowel diseases and irritable bowel syndrome. Impairment of the intestinal epithelial barrier function is a suspected consequence of stress, but the underlying mechanisms remain unclear. This study aimed to determine the mechanisms through which stress modulates the colonic epithelial barrier.

Protective effect of dietary nitrate on experimental gastritis in rats.

Nitrates have long been considered as harmful dietary components and judged responsible for deleterious effects on human health, leading to stringent regulations concerning their levels in food and water. However, recent studies demonstrate that dietary nitrate may have a major role in human health as a non-immune mechanism for host defence, through its metabolism to NO in the stomach. NO is a versatile molecule and although evidence exists showing that administration of low doses of exogenous NO protects against gastrointestinal inflammation, higher NO doses have been shown to exacerbate injury.

Proteinase-activated receptor-2-induced colonic inflammation in mice: possible involvement of afferent neurons, nitric oxide, and paracellular permeability.

Activation of colonic proteinase-activated receptor-2 (PAR-2) provokes colonic inflammation and increases mucosal permeability in mice. The mechanism of inflammation is under debate and could be neurogenic and/or the consequence of tight-junction opening with passage of exogenous pathogens into the lamina propria. The present study aimed to further characterize the inflammatory effect of PAR-2 activation by investigating: 1) the role of NO, 2) the role of afferent neurons, and 3) a possible cause and effect relationship between colonic paracellular permeability changes and mucosal inflammation.

Stress-induced visceral hypersensitivity in female rats is estrogen-dependent and involves tachykinin NK1 receptors.

Hormonal cycling may be related to a higher incidence of pain syndrome in female. As tachykinins are pivotal in stress-induced colonic dysfunction, we investigated whether ovarian steroids influence stress-induced visceral hypersensitivity to rectal distension (RD) in female rats and further, whether this influence involves NK1 receptors. Female Wistar rats, either intact or ovariectomized (OVX), were equipped for abdominal muscle electromyography and submitted to 2-h partial restraint stress (PRS) or sham-PRS.

Alteration of CCK-induced satiety in post-Nippostrongylus brasiliensis-infected rats.

In rats, the nematode Nippostrongylus brasiliensis induces an intestinal inflammation, but after the inflammation had resolved and the worm burden eliminated, morphological alterations of the intestinal wall, mainly consisting of mast cell hyperplasia and enteric nerve remodeling, persist for several weeks. Intestinal signals reaching the brain through the vagus nerve and involving neuropeptides such as CCK, play a role in the control of food intake. Our hypothesis was that neuroimmune alterations of the intestine may alter this control.

Induction of intestinal inflammation in mouse by activation of proteinase-activated receptor-2.

Proteinase-activated receptor (PAR)-2, a G-protein-coupled receptor for trypsin and mast cell tryptase, is highly expressed in the intestine. Luminal trypsin and tryptase are elevated in the colon of inflammatory bowel disease patients. We hypothesized that luminal proteinases activate PAR-2 and induce colonic inflammation.