SummaryInflammatory bowel disease (IBD), a chronic intestinal inflammatory condition that affects millions of people worldwide, results in high morbidity and exorbitant health-care costs. The critical features of both innate and adaptive immunity are to control inflammation and dysfunction in this equilibrium is believed to be the reason for the development of IBD. miR-155, a microRNA, is up-regulated in various inflammatory disease states, including IBD, and is a positive regulator of T-cell responses.

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 colitis-associated 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.

Human Cytomegalovirus (HCMV) is an endemic herpes virus that reemerges in cancer patients enhancing oncogenic potential. HCMV infection is associated with certain types of cancer morbidity such as glioblastomas. HCMV, like all other herpes viruses, has the ability to remain latent within the body of the host and can contribute in chronic inflammation. To determine the role of HCMV in glioma pathogenesis, paraffin-embedded blocks from glioma patients (n = 50) and from benign meningioma patients (n = 30) were obtained and evaluated by immunohistochemistry and polymerase chain reaction for the evidence of HCMV antigen expression and the presence of viral DNA. We detected HCMV antigen and DNA for IEI-72, pp65, and late antigen in 33/36, 28/36, and 26/36 in glioblastoma multiforme patients whereas 12/14, 10/14, and 9/14 in anaplastic astrocytoma patients, respectively. Furthermore, 84% of glioma patients were positive for immunoglobulin G (IgG) compared to 72.5% among control samples (P = 0.04). These data indicate the presence of the HCMV virus in a high percentage of glioma samples demonstrating distinct histopathological grades and support previous reports showing the presence of HCMV infection in glioma tissue. These studies demonstrate that detection of low-levels of latent viral infections may play an active role in glioma development and pathogenesis.

Glioma is the most common and believed to be one of the most aggressive tumors of the central nervous system (CNS) in humans. Very little information is available on the etiology and pathogenesis of these tumors to date. A significant gap remains in our current understanding of the molecular pathways involved in the genesis, progression and clinical behavior of these tumors. Recently, several single nucleotide polymorphisms (SNPs) have been identified in cytokine gene sequences, particularly within the promoter region of these genes, and have been shown to be associated with the development of different types of brain tumors. The present study investigates the association of C-33T SNP in the interleukin-4 (IL-4) gene with systemic IL-4 level and the S503P SNP in the IL-4R gene with the incidence of glioma.Blood samples were collected from 100 histologically confirmed adult patients with glioma, and 30 apparently healthy individuals from the same area. DNA was extracted from each blood sample, and the IL-4 and IL-4R genes were amplified using polymerase chain reaction (PCR) with gene-specific primers. Systemic IL-4 concentration was assessed in serum samples from each participant by enzyme-linked immunosorbent assay (ELISA). We observed a negative association between the homozygous genotype (CC) of the SNP C-33T of the IL-4 gene with the incidence of glioma (OR=0.19, 95% CI=0.035-1.02), while the T allele of the SNP demonstrated a significant protective association against glioma. Similarly, the heterozygous (CT) and homozygous mutant (CC) of the SNP S503P of the IL-4R gene demonstrated a significant association with glioma development (OR=0.405, 95% CI=0.17-0.969 and OR=0.147, 95% CI=0.036-0.6 respectively), while the C allele exhibited a highly significant association with protection from glioma formation.These findings suggest that the T allele of the SNP C-33T in the IL-4 gene and the C allele of the SNP S503P in IL-4R may have a protective role against glioma development.