The bile acid sensor FXR regulates insulin transcription and secretion.

Farnesoid X Receptor plays an important role in maintaining bile acid, cholesterol homeostasis and glucose metabolism. Here we investigated whether FXR is expressed by pancreatic beta-cells and regulates insulin signaling in pancreatic beta-cell line and human islets. We found that FXR activation induces positive regulatory effects on glucose-induced insulin transcription and secretion by genomic and non-genomic activities.

The bile acid receptor FXR is a modulator of intestinal innate immunity.

The farnesoid X receptor (FXR) is a bile acid-regulated nuclear receptor expressed in enterohepatic tissues. In this study we investigated whether FXR is expressed by cells of innate immunity and regulates inflammation in animal models of colitis. Acute (7 days) and chronic (8 wk) colitis were induced in wild-type and FXR(-/-) mice by intrarectal administration of trinitrobenzensulfonic acid or by 7-day administration of 5% dextran sulfate in drinking water.

Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn's disease.

Background & Aims: T-helper (Th)1 cells play a central role in the pathogenesis of tissue damage in Crohn's disease (CD). Interleukin (IL)-12/STAT4 signaling promotes Th1 cell commitment in CD, but other cytokines are needed to maintain activated Th1 cells in the mucosa. In this study, we examined the expression and role of IL-21, a T-cell-derived cytokine of the IL-2 family; in tissues and cells isolated from patients with inflammatory bowel disease.

CARD15 mutation analysis in an Italian population: Leu1007fsinsC but neither Arg702Trp nor Gly908Arg mutations are associated with Crohn's disease.

Background: CARD15 gene mutations have been demonstrated to confer a high risk of Crohn's disease (CD). Despite this, recent studies reported variable associations between CD and CARD15 mutations in distinct ethnic groups, thus raising the hypothesis that genetic and/or allelic heterogeneity may influence the relationship between CARD15 and CD. The purpose of this study was to evaluate the frequency of the main mutations of the CARD15 gene (Leu 1007fsinsC, Arg702Trp, and Gly908Arg) in Italian CD patients and to establish possible genotype-phenotype correlations.

Induction and regulation of Smad7 in the gastric mucosa of patients with Helicobacter pylori infection.

Background & Aims: Helicobacter pylori (Hp) infection causes a chronic gastric inflammation, which can lead to peptic ulceration and cancer. The inflammatory response is multifactorial and is characterized by exaggerated Th1 cytokine production. How the Th1 response is induced and maintained in the stomach of Hp-infected patients remains unclear.

Genetic and pathogenetic insights into inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the gastrointestinal tract that share clinical and pathologic characteristics. The most credible hypothesis is that CD and UC result from an inappropriate and exaggerated mucosal immune response to normal constituents of the mucosal microflora that is in part genetically determined. However, there is reason to believe that the main pathologic processes in these two diseases are distinct.

A failure of transforming growth factor-beta1 negative regulation maintains sustained NF-kappaB activation in gut inflammation.

Immunologically mediated tissue damage in the gut is associated with increased production of proinflammatory cytokines, which activate the transcription factor NF-kappaB in a variety of different cell types. The mechanisms/factors that negatively regulate NF-kappaB in the human gut and the pathways leading to the sustained NF-kappaB activation in gut inflammation remain to be identified. Pretreatment of normal human intestinal lamina propria mononuclear cells (LPMC) with transforming growth factor-beta1 (TGF-beta1) resulted in a marked suppression of TNF-alpha-induced NF-kappaB p65 accumulation in the nucleus, NF-kappaB binding DNA activity, and NF-kappaB-dependent gene activation.

Enhanced expression of interferon regulatory factor-1 in the mucosa of children with celiac disease.

Celiac disease (CD) is an enteropathy characterized by a Th1-type immune response to the dietary gluten. The transcriptional mechanisms or factors that control Th1 cell development in this condition remain to be elucidated. The aim of this study was to analyze in CD the expression of interferon (IFN) regulatory factor (IRF)-1, a transcription factor that regulates the differentiation and function of Th1 cells.

Fecal alpha 1-antitrypsin clearance as a marker of clinical relapse in patients with Crohn's disease of the distal ileum.

Background: Crohn's disease (CD) shows a chronic relapsing course but no marker of relapse is currently available. However, fecal alpha 1-antitrypsin (alpha 1-AT) clearance (alpha 1-ATCl) is an indicator of protein loss and increases during active inflammation. We assessed the usefulness of fecal alpha 1-ATCl in predicting clinical relapse in patients with inactive ileal CD.

Metastatic Crohn's disease of the forehead.

Background: Metastatic Crohn's disease (CD) involves the presence of cutaneous granuloma distant from the intestinal lesions related to the disease, usually observed in colonic CD.

Case History: A 35-year-old female with a permanent ileostomy following proctocolectomy for CD presented in 1999 with a 2-month history of an unusual skin lesion of the forehead. A diagnosis of CD of the ileum, colon, and rectum had been made in 1994.