31 research outputs found
Tu1029 Endoscopic and Surgical Treatment of Malignant Colorectal Polyps: A Population-Based Comparative Study
Su1233 Increased Efficiency in Adenoma Detection With Screening and Surveillance Colonoscopies Over the Course of Scheduled Block
CCR3 Blockade Attenuates Eosinophilic Ileitis and Associated Remodeling
Intestinal remodeling and stricture formation is a complication of inflammatory bowel disease (IBD) that often requires surgical intervention. Although eosinophils are associated with mucosal remodeling in other
organs and are increased in IBD tissues, their role in
IBD-associated remodeling is unclear. Histological and
molecular features of ileitis and remodeling were assessed using immunohistochemical, histomorphometric, flow cytometric, and molecular analysis (real-time
RT-PCR) techniques in a murine model of chronic eosinophilic ileitis. Collagen protein was assessed by Sircol
assay. Using a spontaneous eosinophilic Crohn’s-like
mouse model SAMP1/SkuSlc, we demonstrate an association between ileitis progression and remodeling over
the course of 40 weeks. Mucosal and submucosal eosinophilia increased over the time course and correlated
with increased histological inflammatory indices. Ileitis
and remodeling increased over the 40 weeks, as did
expression of fibronectin. CCR3-specific antibody-mediated reduction of eosinophils resulted in significant decrease in goblet cell hyperplasia, muscularis propria
hypertrophy, villus blunting, and expression of inflammatory and remodeling genes, including fibronectin.
Cellularity of local mesenteric lymph nodes, including
T- and B-lymphocytes, was also significantly reduced.
Thus, eosinophils participate in intestinal remodeling, supporting eosinophils as a novel therapeutic
target
Tu1938 Predictors of Interobserver Variability (IOV) Among Cytopatologists (CyPs) in the Diagnosis of Pancreatic Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-FNA) Cytology Specimens
Esophageal human β-defensin expression in eosinophilic esophagitis.
Background: Defensins are antimicrobial peptides
expressed on mucosal surfaces that contribute to maintaining
intestinal homeostasis by providing innate defense mechanisms for the epithelia. Defensin expression is altered in a number of diseases that affect mucosal surfaces, such as atopic
dermatitis, allergic rhinitis, and inflammatory bowel disease.
Similar to atopic dermatitis, eosinophilic esophagitis (EoE) is
a chronic disease in which the squamous epithelial surface is
affected by a similar TH2 microenvironment and eosinophilpredominant inflammation. Therefore, we hypothesized that
defensin expression would be decreased in EoE.
Methods: To address this, we measured defensin expression
invitro in cell lines derived from patients with EoE (EoE1-T) or gastroesophageal reflux disease (GERD) (NES-G4T cells) and ex vivo
in esophageal mucosal biopsy samples from children with EoE
or GERD and control children without esophageal disease.
Results: Interleukin-5 induced a decrease in human
β-defensin (hBD) -1 and hBD3 expression in EoE1-T but not in
NES-G4T cells. Compared with esophageal biopsy specimens
from GERD and control children, specimens from EoE pediatric
patients revealed a significant decrease in mRNA and protein
expression for hBD1 and hBD3.
Conclusion: Diminished expression of hBD1 and hBD3
may make the esophageal epithelium more susceptible to the
development and/or perpetuation of EoE
Sa1822 Patient Preferences for Prevention of Esophageal Adenocarcinoma in Barrett's Esophagus, Endoscopic Ablation Versus Chemoprevention: A Prospective Multicenter Study
Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis
Objective: Eosinophilic oesophagitis (EoE) is a chronic
inflammatory condition of the oesophagus with limited
treatment options. No previous transgenic model has
specifically targeted the oesophageal mucosa to induce
oesophageal eosinophilia.
Design: We developed a mouse model that closely
resembles EoE by utilising oxazolone haptenation in mice
with transgenic overexpression of an eosinophil poietic
and survival factor (interleukin (IL)-5) in resident
squamous oesophageal epithelia.
Results: Overexpression of IL-5 in the healthy
oesophagus was achieved in transgenic mice (L2-IL5)
using the squamous epithelial promoter Epstein–Barr
virus ED-L2. Oxazolone-challenged L2-IL5 mice
developed dose-dependent pan-oesophageal
eosinophilia, including eosinophil microabscess formation
and degranulation as well as basal cell hyperplasia.
Moreover, oesophagi expressed increased IL-13 and the
eosinophil agonist chemokine eotaxin-1. Treatment of
these mice with corticosteroids significantly reduced
eosinophilia and epithelial inflammation.
Conclusions: L2-IL5 mice provide a novel experimental
model that can potentially be used in preclinical testing
of EoE-related therapeutics and mechanistic studies
identifying pathogenetic features associated with
mucosal eosinophilia
Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis
Objective Eosinophils reside in the colonic mucosa
and increase significantly during disease. Although a
number of studies have suggested that eosinophils
contribute to the pathogenesis of GI inflammation, the
expanding scope of eosinophil-mediated activities
indicate that they also regulate local immune responses
and modulate tissue inflammation. We sought to define
the impact of eosinophils that respond to acute phases
of colitis in mice.
Design Acute colitis was induced in mice by
administration of dextran sulfate sodium, 2,4,6-
trinitrobenzenesulfonic acid or oxazolone to C57BL/6J
(control) or eosinophil deficient (PHIL) mice. Eosinophils
were also depleted from mice using antibodies against
interleukin (IL)-5 or by grafting bone marrow from PHIL
mice into control mice. Colon tissues were collected and
analysed by immunohistochemistry, flow cytometry and
reverse transcription PCR; lipids were analysed by mass
spectroscopy.
Results Eosinophil-deficient mice developed
significantly more severe colitis, and their colon tissues
contained a greater number of neutrophils, than
controls. This compensatory increase in neutrophils was
accompanied by increased levels of the chemokines
CXCL1 and CXCL2, which attract neutrophils. Lipidomic
analyses of colonic tissue from eosinophil-deficient mice
identified a deficiency in the docosahexaenoic acidderived anti-inflammatory mediator 10, 17-
dihydroxydocosahexaenoic acid (diHDoHE), namely
protectin D1 (PD1). Administration of an exogenous
PD1-isomer (10S, 17S-DiHDoHE) reduced the severity of
colitis in eosinophil-deficient mice. The PD1-isomer also
attenuated neutrophil infiltration and reduced levels of
tumour necrosis factor-α, IL-1β, IL-6 and inducible NOsynthase in colons of mice. Finally, in vitro assays
identified a direct inhibitory effect of PD1-isomer on
neutrophil transepithelial migration.
Conclusions Eosinophils exert a protective effect in
acute mouse colitis, via production of anti-inflammatory
lipid mediators