Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), which is
thought to result from immune-mediated inflammatory disorders, leads to high morbidity and health
care cost. Fatty acid amide hydrolase (FAAH) is an enzyme crucially involved in the modulation of intestinal
physiology through anandamide (AEA) and other endocannabinoids. Here we examined the effects of
an FAAH inhibitor (FAAH-II), on dextran sodium sulphate (DSS)-induced experimental colitis in mice.
Treatments with FAAH-II improved overall clinical scores by reversing weight loss and colitisassociated
pathogenesis. The frequencies of activated CD4+ T cells in spleens, mesenteric lymph nodes
(MLNs), Peyer’s patches (PPs), and colon lamina propiria (LP) were reduced by FAAH inhibition.
Similarly, the frequencies of macrophages, neutrophils, natural killer (NK), and NKT cells in the PPs
and LP of mice with colitis declined after FAAH blockade, as did concentrations of systemic and colon
inflammatory cytokines. Microarray analysis showed that 26 miRNAs from MLNs and 217 from PPs
had a 1.5-fold greater difference in expression after FAAH inhibition. Among them, 8 miRNAs were determined
by reverse-transcription polymerase chain reaction (RT-PCR) analysis to have anti-inflammatory
properties. Pathway analysis demonstrated that differentially regulated miRNAs target mRNA associated
with inflammation. Thus, FAAH-II ameliorates experimental colitis by reducing not only the number of
activated T cells but also the frequency of macrophages, neutrophils, and NK/NKT cell, as well as inflammatory
miRNAs and cytokine at effector sites in the colon. These studies demonstrate for the first time
that FAAH-II inhibitor may suppress colitis through regulation of pro-inflammatory miRNAs expression.
Published by Elsevier Inc.
1. Introduction
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2016
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