scholarly journals CARD16 is differentially expressed in the blood of patients with Crohn’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Monozygotic Twins ◽  
Muramyl Dipeptide ◽  
Differentially Expressed ◽  
Peripheral Blood Mononuclear ◽  
Disease Etiology ◽  
Economic Productivity

Crohn’s Disease (CD) is an inflammatory bowel disease that causes significant morbidity, declines in quality of life and loss of economic productivity (1, 2). Twin studies show concordance rates at 58.3% and 63.3% in monozygotic twins demonstrating that genetic factors contribute to the disease etiology in a significant manner (3, 4). We mined a published microarray dataset to perform global differential gene expression profiling using the blood of patients with Crohn’s Disease (5). We identified the caspase recruitment domain family member 16, CARD16, also known as COP and Pseudo-ICE as among the most differentially expressed genes in the blood of patients with Crohn’s Disease. CARD16 expression in the whole blood of patients with Crohn’s Disease was significantly higher than in the blood of healthy, non-affected subjects. Analysis of a separate dataset (6) revealed that CARD16 is a transcriptionally activated in peripheral blood mononuclear cells following stimulation with muramyl dipeptide. CARD16 has been described as both a negative and positive regulator of interleukin-1 𝛃 (IL-1 𝛃) secretion (7, 8) and an activator of NF-kB signaling (9). These data suggest that differential and significantly increased expression of CARD16 in the blood of patients with Crohn’s Disease, in conjunction with the contrasting roles of CARD16 in inflammasome versus NF-kB signaling might contribute to the dysregulated cytokine profile seen in the hematopoietic tissues of patients with Crohn’s Disease (10-15).

scholarly journals The gene encoding the interleukin-1 receptor antagonist is differentially expressed in the blood and regulatory T-cells of patients with Crohn’s disease and transcriptionally induced in peripheral blood mononuclear cells upon stimulation with muramyl dipeptide.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
T Cells ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Muramyl Dipeptide ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Crohn’s disease, an inflammatory bowel disease (1), is a significant cause of morbidity and economic burden in the United States (2, 3, 4). We performed differential gene expression analyses and identified the interleukin-1 (IL-1) receptor antagonist, IL1RN (5, 6), as among the genes most differentially expressed in the blood and regulatory T-cells of patients with Crohn’s disease using published (7) and public datasets (8). Further analysis of published microarray data (9) revealed that IL1RN was transcriptionally induced upon stimulation of peripheral blood mononuclear cells (PBMC) with muramyl dipeptide, the ligand for the gene product of the Crohn’s disease susceptibility locus NOD2. Interestingly, IL-1RN was expressed at significantly lower quantities in the Treg of patients with Crohn’s disease than in the Treg of non-affected control subjects. This is the first report of differential expression of IL1RN in patients with Crohn’s disease.

scholarly journals The gene encoding the Wiskott-Aldrich syndrome (WAS) protein is transcriptionally repressed following stimulation of peripheral blood mononuclear cells with muramyl dipeptide.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Pattern Recognition ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mononuclear Cells ◽  
Muramyl Dipeptide ◽  
Gene Encoding ◽  
Peripheral Blood Mononuclear ◽  
Wiskott Aldrich Syndrome ◽  
Blood Mononuclear Cells

The nucleotide-binding oligomerization domain protein 2, NOD2, is the pattern recognition receptor for muramyl dipeptide, a component of the cell wall of both gram-positive and gram-negative bacteria (1, 2). Sensing of muramyl dipeptide by NOD2 triggers signal transduction downstream of the RIP2 kinase to transcriptionally activate a diverse innate immune gene expression program (3-5). Single nucleotide variants in NOD2 are the strongest genetic risk factors for developing Crohn’s Disease (6, 7), an inflammatory bowel disease (8). By mining a published dataset (9), we found that among the genes whose expression changed most significantly in peripheral blood mononuclear cells (PBMC) stimulated with muramyl dipeptide, genome-wide, was the gene encoding the Wiskott-Aldrich syndrome (WAS) protein (10), a regulator of actin polymerization in hematopoietic cells (11). The WAS gene is mutated in patients with Wiskott-Aldrich syndrome (12), a genetic disorder characterized by thrombocytopenia, eczema, immunodeficiency and lymphoid malignancies (13), and whose symptoms include bloody diarrhea (14, 15). WAS RNA message was transcriptionally repressed following exposure of PBMC to muramyl dipeptide. These data link together a gene, that when mutated in humans leads to gastrointestinal symptoms not dissimilar to those found in patients with Crohn’s Disease, with the ligand for the gene whose product encodes the single most significant genetic variant conferring risk for development of Crohn’s Disease, and further suggest that the actin cytoskeleton may be a central target of gene expression changes effected by NOD2 pattern recognition of MDP.

scholarly journals ZBTB6 is hyper-methylated and differentially expressed in the blood of patients with Crohn’s disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
The United States ◽  
Differentially Expressed ◽  
Economic Productivity ◽  
Unbiased Manner ◽  
Inflammatory Bowel ◽  
Disease Analysis ◽  
Broad Complex

Crohn’s disease, an inflammatory bowel disease of the gastrointestinal tract (1), causes significant morbidity and nearly 3.5 billion dollars in lost economic productivity in the United States (2) due to complications of the disease. We mined transcriptome and methylome datasets (3, 4) to understand, in an unbiased manner, the most significant changes in gene expression and DNA methylation in the hematopoietic system of patients with Crohn’s disease (CD). We identified the zinc finger and BTB (broad complex, tramtrack, bric-à-brac) domain-containing gene ZBTB6 (5, 6) as one of the most differentially expressed genes in the whole blood of patients with Crohn’s disease. Analysis of a separate data revealed that the ZBTB6 locus was one of the most differentially methylated sites globally in the blood of patients with Crohn’s disease when compared to the blood of healthy patients. ZBTB6 is differentially methylated and differentially expressed in the blood of patients with Crohn’s disease, and more significantly so than the vast majority of the human genome. These data point to inhibition of ZBTB6 gene expression by hyper-methylation of the ZBTB6 locus and suggest that titration of some function or transcriptional target of ZBTB6 may be an important event in the pathogenesis of Crohn’s disease.

scholarly journals Differential between Protein and mRNA Expression of CCR7 and SSTR5 Receptors in Crohn's Disease Patients

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Nathalie Taquet ◽  
Serge Dumont ◽  
Jean-Luc Vonesch ◽  
Didier Hentsch ◽  
Jean-Marie Reimund ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Protein Expression ◽  
Mrna Expression ◽  
Large Scale ◽  
Mononuclear Cells ◽  
Biologically Active ◽  
Chronic Inflammatory Bowel Disease ◽  
Peripheral Blood Mononuclear ◽  
Mrna And Protein Expression

Crohn's disease (CD) is a multifactorial chronic inflammatory bowel disease of unknown cause. The aim of the present study was to explore if mRNA over-expression of SSTR5 and CCR7 found in CD patients could be correlated to respective protein expression. When compared to healthy donors, SSTR5 was over-expressed 417±71 times in CD peripheral blood mononuclear cells (PBMCs). Flow cytometry experiments showed no correlation between mRNA and protein expression for SSTR5 in PBMCs. In an attempt to find a reason of such a high mRNA expression, SSTR5 present on CD PBMCs were tested and found as biologically active as on healthy cells. In biopsies of CD intestinal tissue, SSTR5 was not over-expressed but CCR7, unchanged in PBMCs, was over-expressed by 10±3 times in the lamina propria. Confocal microscopy showed a good correlation of CCR7 mRNA and protein expression in CD intestinal biopsies. Our data emphasize flow and image cytometry as impossible to circumvent in complement to molecular biology so to avoid false interpretation on receptor expressions. Once confirmed by further large-scale studies, our preliminary results suggest a role for SSTR5 and CCR7 in CD pathogenesis.

scholarly journals CircRNA_103765 acts as a proinflammatory factor via sponging miR-30 family in Crohn’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yulan Ye ◽  
Liping Zhang ◽  
Tong Hu ◽  
Juan Yin ◽  
Lijuan Xu ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Cell Apoptosis ◽  
Mononuclear Cells ◽  
Circular Rnas ◽  
Infliximab Treatment ◽  
Peripheral Blood Mononuclear ◽  
Novel Approach ◽  
Tnf Α

AbstractIncreasing evidence suggests that circular RNAs (circRNAs) play critical roles in various pathophysiological activities. However, the role of circRNAs in inflammatory bowel disease (IBD) remains unclear. Here we report the potential roles of hsa_circRNA_103765 in regulating cell apoptosis induced by TNF-α in Crohn’s disease (CD). We identify that CircRNA_103765 expression was significantly upregulated in peripheral blood mononuclear cells (PBMCs) of patients with active IBD. A positive correlation with TNF-α significantly enhanced circRNA_103765 expression in CD, which was significantly reversed by anti-TNF-α mAb (infliximab) treatment. In vitro experiments showed that TNF-α could induce the expression of circRNA_103765, which was cell apoptosis dependent, while silencing of circRNA_103765 could protect human intestinal epithelial cells (IECs) from TNF-α-induced apoptosis. In addition, circRNA_103765 acted as a molecular sponge to adsorb the miR-30 family and impair the negative regulation of Delta-like ligand 4 (DLL4). Collectively, CircRNA_103765 is a novel important regulator of the pathogenesis of IBD via sponging miR-30 family-mediated DLL4 expression changes. Blockade of circRNA_103765 could serve as a novel approach for the treatment of IBD patients.

Sign in / Sign up

Export Citation Format

Share Document