Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Intestinal Inflammation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources
PubMed1997

Acute and chronic effects of different bile acids on indomethacin-induced intestinal inflammation.

The role of bile acids in the pathogenesis of bowel inflammation is unknown. The objective of this study was to determine whether urso- (UDC), cheno- (CDC), and taurochenodeoxycholic acid (TCDC) exert a pro- or antiinflammatory action in the acute and chronic phase of the indomethacin model of a long lasting ileitis in rats. Short-term and long-term inflammatory responses (48 h and 10 days, respectively) after two subcutaneous indomethacin (Indo) injections were elicited in rat small bowel and mesentery. To distinguish between common and model-specific effects bile acids were tested also in another model of acute inflammation induced by mesenteric superfusion with leukotriene B4(LTB4). The number of adherent and emigrated leukocytes, leukocyte rolling velocity, and venular wall shear rate were monitored in normal and inflamed postcapillary venules, and fecal pH of ileal contents which has been shown to correlate with degree of inflammation was measured, 6.5- and 2.3-fold increases in leukocyte adherence and comparable increments in leukocyte emigration were observed 48 h and ten days after indomethacin treatment, respectively. UDC, CDC, and TCDC (10 mg/kg) given daily from Indo administration until the experiment attenuated the leukocyte adherence and emigration responses elicited by indomethacin in short- and long-term inflammation. This effect was accompanied by a significant increase of fecal pH which had been lowered by indomethacin. None of the bile acids reduced the LTB4-induced increases in adherence and emigration. Oral administration of UDC, CDC, and TCDC reduces leukocyte adhesion and emigration in acute and chronic stages of Indo-induced inflammation. This could be due to the alkalizing effect of these bile acids on fecal pH which has been shown to correlate with a decrease of leukocyte-endothelial cell interactions but--according to the missing effectiveness in another model of intestinal inflammation--not to specific influences on leukocyte-endothelial cell adhesion.

Animals↗
PubMed2006

Intestinal inflammation modulates expression of 11beta-hydroxysteroid dehydrogenase in murine gut.

The effect of glucocorticoids is controlled at the pre-receptor level by the activity of 11beta-hydroxysteroid dehydrogenase (11HSD). The isoform 11HSD1 is an NADP+ -dependent oxidoreductase, usually reductase, that amplifies the action of glucocorticoids due to reduction of the biologically inactive 11-oxo derivatives cortisone and 11-dehydrocorticosterone to cortisol and corticosterone. The NAD+ -dependent isoform (11HSD2) is an oxidase that restrains the effect of hormones due to 11beta-oxidation of cortisol and corticosterone to their 11-oxo derivatives. Although the immunosuppressive and anti-inflammatory effects of glucocorticoids are well known, the relationship between inflammation and local metabolism of glucocorticoids is not well understood. In this study, we demonstrated that colitis induced by dextran sulfate sodium modulates colonic 11HSD1. Experimentally induced intestinal inflammation stimulated colonic NADP+ -dependent but not NAD+ -dependent 11HSD activity. Colonic 11HSD1 mRNA was increased, whereas 11HSD2 mRNA was not changed. Additional parallel studies revealed a similar pattern of 11HSD1 mRNA induction in mesenteric lymph nodes and intestinal intraepithelial lymphocytes, but not in spleen and peritoneal macrophages. These data suggest that inflammation modulates local metabolism of glucocorticoid and support the notion that pre-receptor regulation of endogenous corticosteroids might play a role in inflammatory processes.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Diarrhea associated with intestinal inflammation increases the potency of mu and delta opioids on the inhibition of gastrointestinal transit in mice.

The aim of the study was to determine the effects of intestinal inflammation induced by croton oil on the antitransit action of systemically administered receptor-specific opioids. Our hypothesis was that inflammation would "sensitize" opioid receptors in peripheral and/or central terminals of myenteric and submucous plexus neurons and enhance the effects of exogenously administered opioids. Diarrhea was induced by p.o. administration of croton oil and was demonstrated by weight loss and increased gastrointestinal transit. Histologically, an increased number of clear vesicles in the cytoplasm of jejunal epithelial cells and enlarged spaces filled with fine granular material in the extravascular compartment were observed. Subcutaneous morphine and fentanyl produced dose-related inhibitions of gastrointestinal transit in saline-treated controls with ED50 values of 1.24 +/- 0.06 and 0.036 +/- 0.010 mg/kg, respectively. In animals with diarrhea, dose-response curves were parallel and shifted to the left with a significant decrease in ED50 values of 2.95 times for morphine and 1.89 for fentanyl. The effects of the delta agonist Tyr-D-Pen-Gly-Phe-D-Pen, but those of U50,488H [trans-3,4-dichloro-N-methyl-N-(2-(1-pyrrolydynil)cyclohexyl) benzeneazetamine] also were increased significantly during diarrhea associated with inflammation. Naloxone (0.1 mg/kg), MR-2266 [(-)-a-5,9-diethyl-2'-hydroxy-2-(3-furylmethyl)-6,7-benzomorphan] (3 mg/kg) and naltrindole (1 mg/kg) antagonized the effects of the receptor-specific opioid agonists used in the study. Our results show that the potency of s.c. mu and delta opioids is increased during inflammation of the gut and that the effect is mediated by the same type of opioid receptors present in the noninflamed tissue. These results support the view that a sensitization of opioid receptors occurs during acute inflammation of the gut.

Amino Acid Sequence↗
PubMed2000

Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation.

It is now clear that functionally specialized regulatory T (Treg) cells exist as part of the normal immune repertoire, preventing the development of pathogenic responses to both self- and intestinal antigens. Here, we report that the Treg cells that control intestinal inflammation express the same phenotype (CD25(+)CD45RB(low)CD4(+)) as those that control autoimmunity. Previous studies have failed to identify how CD25(+) Treg cells function in vivo. Our studies reveal that the immune-suppressive function of these cells in vivo is dependent on signaling via the negative regulator of T cell activation cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), as well as secretion of the immune-suppressive cytokine transforming growth factor beta. Strikingly, constitutive expression of CTLA-4 among CD4(+) cells was restricted primarily to Treg cells, suggesting that CTLA-4 expression by these cells is involved in their immune-suppressive function. These findings raise the possibility that Treg cell function contributes to the immune suppression characteristic of CTLA-4 signaling. Identification of costimulatory molecules involved in the function of Treg cells may facilitate further characterization of these cells and development of new therapeutic strategies for the treatment of inflammatory diseases.

Abatacept↗
PubMed1992

Epithelial proliferation in response to gastrointestinal inflammation.

Intestinal inflammation seems invariably to be associated with increased epithelial proliferation. In the small bowel the pathological consequences of this area an increase in the crypt proliferative compartment and a decrease in the absorptive villus compartment, which can lead to malabsorption. In the colon, it is more difficult to examine changes in cell proliferation, but using Ki67, epithelial proliferation has been shown to be increased in ulcerative colitis and parasitic infection. The teleological advantage of increasing epithelial proliferation during intestinal inflammation is presumably in an effort to get rid of parasitized or infected epithelial cells, or to rapidly replace cells which have been lost. Rejection of helminth parasites from rodent small bowel is associated with partial villous atrophy and crypt hypertrophy, which is probably part of the host response making the mucosa inhospitable to the parasites. The short-term nutritional disadvantage of malabsorption is outweighed by the long-term advantage of being parasite-free. However, when the intestinal inflammation is elicited by a dietary constituent, the consequences are only pathological. At the moment there is no information as to the mechanisms by which inflammatory cells alter mucosal morphology and epithelial renewal. The restructuring of mucosal morphology in the flat-mucosa involves considerable adaptation of the connective tissue elements of the lamina propria. Whether this occurs in response to changes in epithelial renewal is not known. Finally, it is clear that activated T cells in the lamina propria can produce a flat-mucosa. In diseases such as Trichuris dysentery and ulcerative colitis there is no or very little T cell activation, even though epithelial proliferation is increased. Increased epithelial proliferation therefore may occur in response to different inflammatory stimuli.

Animals↗
PubMed2004

Intestinal inflammation measured by fecal neopterin in Gambian children with enteropathy: association with growth failure, Giardia lamblia, and intestinal permeability.

OBJECTIVES: Investigate whether fecal neopterin concentration (a potential marker of gut inflammation) in Gambian children with enteropathy was associated with growth failure. Secondary outcome measures tested the associations between Giardia lamblia infestation, fecal neopterin and lactulose mannitol absorption ratio(L:M), a measure of intestinal permeability. METHODS: Seventy-two children had height and weight measured every 6 to 8 weeks until 15 months of age in a rural Gambian village. L:M ratio, a measure of small intestinal permeability and fecal neopterin were measured at these times. Stool was examined by immunofluorescence and light microscope for Giardia cysts. RESULTS: Long-term height and weight gains were negatively associated with mean subject fecal neopterin concentration (r = -0.29 and -0.36, respectively; P < 0.001). There was no correlation between fecal neopterin and intestinal permeability or history of diarrhea. Of 72 children studied, 19 had Giardia cysts in stool and 38 had negative stool examinations. Infected children had a mean of 0.7 days of diarrhea/week (95% confidence interval [CI], 0.31-1.03) versus 0.8 days/week (95% CI, 0.71-0.85) in uninfected children. No difference in growth was detected between those with positive or negative fecal smears. Mean L:M ratio was the same in both groups (0.31; 95% CI, 0.26-0.34). CONCLUSIONS: Consistent with the theory that intestinal inflammation in tropical infants may impair growth, fecal neopterin concentrations were inversely associated with growth. Factors other than Giardia are causing enteropathy and growth failure in Gambian infants.

Animals↗
PubMed2005

Signal transducers and activators of transcription 3 signaling pathway: an essential mediator of inflammatory bowel disease and other forms of intestinal inflammation.

Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of chronic inflammatory bowel disease (IBD), are characterized by mucosal immune cell activation that is driven by a cytokine imbalance. Several cytokines involved in IBD act through the activation of the signal transducers and activators of transcription (STAT) family. We investigated the activation of STAT3 in the mucosa of CD and UC patients, and evaluated whether this event is specific for IBD patients. Using immunofluorescence and immunoblotting, total and phosphorylated STAT3 levels were assessed in biopsy specimens, isolated lamina propria mononuclear cells, and peripheral blood mononuclear cells from patients with CD, UC, other forms of intestinal inflammation, and control subjects. Immunoblotting revealed phosphorylated STAT3 in mucosal biopsy specimens from patients with CD, UC, celiac disease, and acute self-limited colitis, but not in the normal mucosa of control subjects. In IBD patients, STAT3 activation was confined to actively inflamed areas. Accordingly, activated STAT3 was detected in isolated lamina propria mononuclear cells from inflamed IBD tissues, but not in peripheral blood mononuclear cells from control subjects or IBD patients. Immunofluorescence demonstrated that the sources of activated STAT3 were macrophages and T lymphocytes, but not neutrophils. STAT3 activation also was detected in T cells infiltrating the duodenal mucosa of celiac disease patients. We conclude that STAT3 signaling occurs in both CD and UC, where it is strictly confined to areas of active inflammation and is limited to infiltrating macrophages and T cells. The occurrence of STAT3 signaling in other acute and chronic intestinal inflammatory conditions suggests that, rather than a specific feature of IBD, it represents a fundamental signaling pathway that is shared by multiple forms of gut inflammation.

Adult↗
PubMed1996

Role of interleukin 8 on leucocyte-endothelial cell adhesion in intestinal inflammation.

BACKGROUND: An important action of interleukin 8 (IL8) is stimulation of granulocytes. The object of this study was to assess the contribution of IL8 to the leucocyte-endothelial cell interactions associated with intestinal inflammation in the rat. METHODS: Two indomethacin injections (48 and 24 hours prior to the experiments) induced a longlasting ileitis in rats. The number of adherent and emigrated leucocytes, leucocyte rolling velocity, and shear rate were monitored in normal and inflamed mesenteric postcapillary venules. Some animals received a monoclonal antibody (MAb) against IL8 or CD11b/CD18 at 24 and 12 hours prior to the experiment. RESULTS: Indomethacin elicited a seven-fold increase in leucocyte adherence and a 5.4-fold increase in leucocyte emigration, while leucocyte rolling velocity was reduced by nearly 80%. The indomethacin induced increases in leucocyte adherence and emigration were significantly reduced (by 57% and 67%, respectively) while leucocyte rolling velocity was increased (to 63% of control) by the IL8-specific MAb. The level of inhibition seen with the IL8 MAb was similar to that associated with administration of a MAb directed against the leucocyte adhesion molecule CD11b/CD18. CONCLUSIONS: IL8 contributes to the leucocyte-endothelial cell interactions elicited in mesenteric venules by indomethacin.

Animals↗
PubMed2002

Intestinal inflammation modulates expression of the synaptic vesicle protein neuronal calcium sensor-1.

The calcium-binding protein neuronal calcium sensor 1 (NCS-1) is involved in modulation of neurotransmitter release in the peripheral and central nervous systems. Since intestinal inflammation impairs neurotransmitter release, we evaluated the expression of NCS-1 in the normal rat colon and in dinitrobenzene sulfonic acid (DNBS)-induced colitis. Immunocytochemistry and Western blots showed high levels of NCS-1 in the myenteric plexus and in axons in the smooth muscle layers; 23 +/- 2% of myenteric neurons were NCS-1 positive, with staining restricted to the largest neurons. NCS-1-positive axons decreased to 13.3 +/- 0.4% of total axons by day 2 and dropped further to 7.0 +/- 0.1% by day 4, returning to control levels by day 16. Dual-label Western blot analysis showed that the expression of NCS-1 relative to PGP 9.5 decreased by 50% on day 4 but returned to control by day 16. The selective loss of NCS-1 during colitis may underlie the altered neural function seen in the inflamed intestine.

Animals↗
PubMed2000

Intestinal inflammation and morphine tolerance alter the interaction between morphine and clonidine on gastrointestinal transit in mice.

BACKGROUND: Morphine and clonidine show synergy or antagonism inhibiting gastrointestinal transit depending on their proportion and level of effect. Their interaction during morphine tolerance and intestinal inflammation were assessed. METHODS: Gastrointestinal transit in mice was evaluated with charcoal and antitransit effects expressed as percent mean values +/- SEM. Tolerance was induced with a morphine pellet (75 mg) implanted for 72 h, and inflammation with intragastric croton oil. Dose-response curves for morphine and clonidine alone and combined at a 1:1 potency ratio were obtained, and doses producing a 50% and 60% inhibition were calculated (ED50, ED60). Interaction was established by isobolograms, interaction indexes, and analysis of variance. RESULTS: In naive and tolerant mice, the combination induced linear dose-response curves up to the ED60 and then reached a plateau. In naive mice, ED50 values were as follows: morphine 1.52 +/- 0.15 mg/kg, clonidine 0.09 +/- 0.008 mg/kg, and combined 0.506 +/- 0.084 mg/kg (0.478 +/- 0.08 mg/kg morphine plus 0.028 +/- 0.004 mg/kg clonidine). During tolerance, ED50 values were as follows: morphine 9.73 +/- 0.8 mg/kg, clonidine 0.09 +/- 0.007 mg/kg, combination 0.131 +/- 0.09 mg/kg (morphine 0. 13 +/- 0.09 mg/kg plus clonidine 0.0013 +/- 0.0005 mg/kg). In both groups, the interaction was synergistic up to the ED60 and antagonistic thereafter; synergy was enhanced during tolerance. During inflammation, ED50 values were as follows: morphine 0.17 +/- 0.04 mg/kg, clonidine 0.015 +/- 0.006 mg/kg, combined 0.62 +/- 0.04 mg/kg (morphine 0.568 +/- 0.04 mg/kg plus clonidine 0.052 +/- 0.004 mg/kg); thus, potencies of morphine and clonidine increased 9.3 and 7.1 times, while the combination remained unaltered. Moreover, inflammation transformed synergy into antagonism. CONCLUSIONS: The interaction between morphine and clonidine was significantly altered during tolerance and inflammation. During tolerance, synergy was present up to 60% effect and then became antagonistic. Inflammation converted synergy to antagonism. A common pathway in signal transduction could partially explain the results.

Analgesics↗
PubMed2004

Leptin receptor expression on T lymphocytes modulates chronic intestinal inflammation in mice.

BACKGROUND: Leptin regulates appetite through the long isoform of its receptor in the hypothalamus. Although leptin regulates immune responses, it is still unknown whether a direct effect of leptin on lymphocytes is required. AIMS: To clarify whether expression of leptin receptors on T lymphocytes modulates intestinal inflammation in mice. METHODS: The model of colitis induced by transfer of CD4(+)CD45RB(high) (RB(high)) cells into scid mice was used. Wild-type (WT) or leptin receptor deficient (db/db) RB(high) cells were transferred into scid mice and development of colitis evaluated. RESULTS: Leptin receptors were expressed on both RB(high) and RB(low) cells. Intestinal lymphocytes of mice with colitis expressed high leptin levels compared with healthy controls whereas the opposite was true for serum leptin levels. Transfer of RB(high) cells from db/db mice induced delayed disease compared with transfer of WT cells. A high rate of apoptosis in lamina propria lymphocytes and reduced cytokine production were observed early on in scid mice receiving db/db RB(high) cells. These effects were not due to the high levels of glucocorticoids present in db/db mice as administration of corticosterone to WT mice failed to reproduce this phenomenon. High expression of peroxisome proliferator activated receptor gamma was observed in the colon of recipients of db/db compared with WT cells. Freshly isolated db/db RB(high) cells produced low levels of interferon gamma. Despite delayed onset of colitis, as disease progressed differences between mice receiving WT or db/db cells were no longer apparent. CONCLUSIONS: These results suggest that leptin affects the immune response, partly by acting on the long isoform of its receptor expressed on T lymphocytes.

Animals↗
PubMed1995

Mucosal imbalance of IL-1 and IL-1 receptor antagonist in inflammatory bowel disease. A novel mechanism of chronic intestinal inflammation.

The etiology and pathogenesis of inflammatory bowel disease (IBD) are unknown. Increasing evidence supports the theory that chronic IBD is the result of dysfunctional immunoregulation manifested by an inappropriate production of mucosal cytokines. The aim of the present study was to test the hypothesis that a specific mucosal imbalance of IL-1 and IL-1 receptor antagonist (IL-1ra) production plays an important role in the perpetuation and chronicity of intestinal inflammation. Total IL-1, IL-1ra, and the IL-1ra/IL-1 ratio were measured in freshly isolated intestinal mucosal cells, as well as in mucosal biopsies obtained from control, Crohn's disease, and ulcerative colitis patients. IL-1 alpha, IL-1 beta, and IL-1 ra were measured by specific non-cross-reacting radioimmunoassays and ELISA. A markedly significant decrease in the intestinal mucosal IL-1ra/IL-1 ratio was found in both Crohn's disease and ulcerative colitis patients when compared with control subjects (p < 0.01). The IL-1ra/IL-1 ratio correlated closely with the clinical severity of disease (r = -0.7846, p < 0.001). Furthermore, the observed decrease in the IL-1ra/IL-1 ratio was specific for IBD because a decreased IL-1ra/IL-1 ratio was not found in patients with self-limiting colitis. These results support the hypothesis that an imbalance between IL-1 and IL-1ra production is of pathogenic importance in chronic inflammatory diseases, including IBD.

Adolescent↗
PubMed2003

Lipoxins: pro-resolution lipid mediators in intestinal inflammation.

Many inflammatory processes are self-limiting, suggesting the existence of endogenous anti-inflammatory mechanisms. Among the lipid mediators generated during cell-cell interactions are the lipoxins (LX, including LXA(4) and B(4)), a distinct class of lipoxygenase-derived eicosanoids. Aspirin acetylation of cyclooxygenase 2 also promotes the generation of a series of 15-epimers of LXA(4), known as aspirin-triggered lipoxins (ATL), that may account for some of the bioactivity profile of aspirin and possibly of nonsteroidal anti-inflammatory drugs. Native LX are rapidly inactivated in vivo, and stable analogs of LXA(4), LXB(4), and ATL have been synthesized that possess enhanced bioavailability and potency as anti-inflammatory eicosanoids. Here, we review current in vitro, ex vivo, and in vivo evidence supporting cytoprotective and proresolution roles for LX in intestinal inflammation. LXA(4), LXA(4) analogs, and ATL analogs inhibit neutrophil chemotaxis, adhesion to epithelium, and epithelial cell chemokine release. In addition, LX blunt TNF-alpha-stimulated inflammatory responses, cyclooxygenase product generation, and epithelial cell apoptosis and are cytoprotective for cytokine-activated colonic mucosa ex vivo. LX, ATL, and synthetic LX analogs have already been demonstrated to possess impressive antiinflammatory and proresolution efficacy in a range of experimental models of inflammation in vivo. Further elucidation of the role of LX in intestinal epithelial cell biology and immune function may yield novel therapeutic approaches in inflammatory bowel disease and possibly gastrointestinal cancer.

Animals↗
PubMed1988

Plasma kinin-precursor levels in clinical intestinal inflammation.

Plasma kinin-precursor (kininogen) concentrations were measured in the peripheral venous blood of 7 untreated patients with inflammatory bowel diseases, 12 healthy subjects, and 5 uncomplicated fracture cases. The mean plasma kininogen levels were significantly raised (P less than 0.025) in patients with intestinal inflammation (7.0 +/- 1.0 micrograms BK Eq/ml), as compared with the value found in healthy subjects (5.7 +/- 0.7 micrograms BK Eq/ml), and in fracture cases (5.0 +/- 1.2 micrograms BK Eq/ml). The packed cell volume did not differ (P greater than 0.05) between patients and control groups. Thus, the raised plasma kininogen levels observed in patients were not the result of nonspecific changes in plasma volume. It is suggested that raised plasma kininogen might be due to increased synthesis to provide substrate for excessive kinin-formation, to a potent inflammatory agent, or to high synthesis of acute-phase reactants. The possible significance of this observation is discussed.

Acute-Phase Reaction↗
PubMed1996

Local production of corticotropin releasing hormone is increased in experimental intestinal inflammation in rats.

BACKGROUND/AIMS: Corticotropin releasing hormone (CRH) suppresses immunological functions via stimulation of the pituitary-adrenal axis, but is also found in peripheral tissues. Peripheral proinflammatory activity of CRH is suggested by increased tissue concentrations in arthritis and in vitro immunostimulatory effects. This study evaluated intestinal CRH concentrations, immunolocalisation, and synthesis in chronic enterocolitis and investigated in vitro responsiveness of lamina propria mononuclear cells to CRH. METHODS: Chronic granulomatous enterocolitis was induced by intramural injection of peptidoglycan-polysaccharide polymers in the ileocaecal region of Lewis rats. CRH protein was measured in caecal specimens by immunohistochemistry and radioimmunoassay and caecal CRH mRNA expression was analysed by reverse transcriptase polymerase chain reaction. RESULTS: In the chronically inflamed caecum abundant immunoreactive CRH was found in inflammatory cells, mesenchymal cells, as well as in myenteric plexi. In contrast, only a few CRH containing cells were detected in normal and HSA injected control caecums. Moreover, caecal CRH protein levels were increased during chronic enterocolitis. Local CRH synthesis as indicated by mRNA expression was considerably increased in chronic enterocolitis whereas it was undetectable or low in uninflamed caecum. In addition, CRH stimulated in vitro proliferation of lamina propria mononuclear cells and inhibited mitogen induced proliferation. CONCLUSION: Increased CRH protein and mRNA expression in chronic enterocolitis and responsiveness of intestinal mononuclear cells to CRH indicate an immunomodulatory role for locally produced CRH in intestinal inflammation.

Animals↗
PubMed2006

Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease.

Calprotectin is an abundant neutrophil protein found in both plasma and stool that is markedly elevated in infectious and inflammatory conditions, including inflammatory bowel disease (IBD). We conducted a systematic review of the published literature regarding fecal calprotectin to evaluate its potential as a noninvasive marker of neutrophilic intestinal inflammation. Reference ranges for fecal calprotectin have been established in healthy adults and children, and elevated concentrations of fecal calprotectin have been demonstrated in numerous studies of patients with IBD. Fecal calprotectin correlates well with histological inflammation as detected by colonoscopy with biopsies and has been shown successfully to predict relapses and detect pouchitis in patients with IBD. Fecal calprotectin has been shown to consistently differentiate IBD from irritable bowel syndrome because it has excellent negative predictive value in ruling out IBD in undiagnosed, symptomatic patients. Fecal calprotectin also may be useful in determining whether clinical symptoms in patients with known IBD are caused by disease flares or noninflammatory complications/underlying irritable bowel syndrome and in providing objective evidence of response to treatment. Although more studies are needed to define fully the role of fecal calprotectin, convincing studies and growing clinical experience point to an expanded role in the diagnosis and management of IBD.

Biomarkers↗
PubMed2001

Consequences of intestinal inflammation on the enteric nervous system: neuronal activation induced by inflammatory mediators.

The ENS is responsible for the regulation and control of all gastrointestinal functions. Because of this critical role, and probably as a consequence of its remarkable plasticity, the ENS is often relatively well preserved in conditions where the architecture of the intestine is seriously disrupted, such as in IBD. There are structural and functional changes in the enteric innervation in animal models of experimental intestinal inflammation and in IBD. These include both up and down regulation of transmitter expression and the induction of new genes in enteric neurons. Using Fos expression as a surrogate marker of neuronal activation it is now well established that enteric neurons (and also enteric glia) respond to inflammation. Whether this "activation" is limited to a short-term functional response, such as increased neuronal excitability, or reflects a long-term change in some aspect of the neuronal phenotype (or both) has yet to be firmly established, but it appears that enteric neurons are highly plastic in their response to inflammation.

Animals↗
PubMed2026

UHRF1 deficiency exacerbates intestinal inflammation by epigenetic modulation of NPY1R gene methylation.

Epigenetic modifications play a crucial role in the pathogenesis of inflammatory bowel disease (IBD) by mediating gene-environment interactions. We previously showed that UHRF1, a central regulator of DNA methylation, contributes to cancer progression; however, its function in IBD remains poorly understood. Here, we revealed that UHRF1 was frequently reduced in inflamed tissues of patients with IBD and that its deficiency exacerbated intestinal epithelial cell (IEC) damage. Through a multilevel approach incorporating human cell models and an intestinal epithelial-specific Uhrf1-KO mouse model, we established UHRF1 as a key mitigator of IBD progression. Mechanistically, UHRF1 bound to the NPY1R promoter, promoted its methylation, and led to transcriptional suppression. The NPY1R upregulation resulting from UHRF1 deficiency attenuated cAMP/PKA/CREB signaling in IECs, thereby enhancing NF-&#x3ba;B activation and subsequent proinflammatory responses, which compromised intestinal epithelial barrier integrity. Furthermore, we identified miR-141 as a negative regulator of NPY1R, highlighting its potential as a therapeutic agent. Collectively, our results identified the UHRF1/NPY1R regulatory axis as a critical epigenetic mechanism in intestinal inflammation and underscored its dual promise for IBD diagnostics and therapy.

Animals↗