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.

In vitro immunomodulation of RH IL-10 on TNF-α secretion by lamina propria mononuclear cells in Crohn's disease

1998 ◽  
Vol 114 ◽  
pp. A1079
Author(s):  
A. Schmit ◽  
M. Carol ◽  
A. Van Gossum ◽  
M. Goldman ◽  
F. Mascart-Lemone
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Lamina Propria ◽  
Mononuclear Cells ◽  
Lamina Propria Mononuclear Cells ◽  
Tnf Α

scholarly journals Effect of Anti-TNF Therapy on Mucosal Apoptosis Genes Expression in Crohn's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Liliana Lykowska-Szuber ◽  
Michal Walczak ◽  
Marzena Skrzypczak-Zielinska ◽  
Joanna Suszynska-Zajczyk ◽  
Kamila Stawczyk-Eder ◽  
...  
Keyword(s):  
Gene Expression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mononuclear Cells ◽  
Mrna Level ◽  
Colon Tissue ◽  
Peripheral Blood Mononuclear ◽  
Effective Response ◽  
Genes Expression

Crohn's disease (CD) is a chronic immune-mediated disorder for which there is not a fully effective treatment. Moreover, biological therapy with anti-tumor necrosis factor-α (anti-TNF-α) monoclonal antibodies leads to an effective response in only 60–70% of patients. Our previous data suggested that specific loci polymorphism of the TNFRSF1B, FCGR3A, IL1R, IL1B, and FAS genes could be a predictor of the primary non-response to anti-TNF therapy in CD patients. In this work, we propose to explain this hypothesis by functional analysis in colon biopsies and in a cell culture model. Using the RT-qPCR analysis, we estimated the FCGR3A, IL1R, TNFRSF1B, IL1B, FAS, and ADAM17 genes mRNA level in colon biopsies material from inflamed and non-inflamed tissue from 21 CD patients (14 responders and 7 non-responders to anti-TNF therapy) and 6 controls, as well as in vitro in a peripheral blood mononuclear cells (PBMCs) from 14 CD patients (seven responders and seven non-responders to anti-TNF therapy) and eight controls cultured for 72 h with 10 μg/ml of anti-TNF antibody. Our findings demonstrated a significant down-regulation of TNFRSF1B gene expression in non-responders both in inflamed and in non-inflamed colon tissue, while the expression of the FCGR3A and IL1B genes was significantly up-regulated in non-responders in the inflamed colon region. In vitro research results indicate that the anti-TNF drug induced a significant decrease in TNFRSF1B, FCGR3A, and FAS gene expression in non-responders. These results show that altered TNFRSF1B, FCGR3A, and IL1B genes expression can be a predictor of the primary non-response to anti-TNF therapy in CD patients.

Infliximab, Immunomodulators and Treatment Failures in Paediatric and Adolescent Patients with Crohn’s Disease: a Nationwide Cohort Study

2020 ◽  
Author(s):  
Ken Lund ◽  
Michael Due Larsen ◽  
Torben Knudsen ◽  
Jens Kjeldsen ◽  
Rasmus Gaardskær Nielsen ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Combination Therapy ◽  
Cox Regression ◽  
Clinical Information ◽  
Infliximab Therapy ◽  
Infliximab Treatment ◽  
Tnf Α ◽  
Adolescent Patients ◽  
Switching Type

Abstract Background and Aims In paediatric patients with Crohn’s disease, the role of combination therapy, infliximab plus immunomodulators [thiopurine or methotrexate], is debated and data are sparse. We examined whether infliximab plus immunomodulators, compared to infliximab therapy alone, reduces the risk of treatment failure measured by intestinal surgery or switching type of anti-tumour necrosis factor [TNF] α agent within 24 months. Design Using Danish registries, we identified patients with Crohn’s disease, aged ≤ 20 years at the time of the first infliximab treatment, and retrieved data on their co-medications. We used Cox regression models to examine surgery or switching type of anti-TNFα agent from January 1, 2003 to December 31, 2015. Results We included 581 patients. The 2-year cumulative percentage of surgery was 8.5% among patients receiving combination therapy and 14.5% in those receiving infliximab alone. The adjusted 2-year hazard ratio [HR] of surgeries was 0.53 (95% confidence interval [CI] 0.32–0.88) in patients receiving combination therapy, compared to patients receiving infliximab alone. When examining a switch of anti-TNFα we included 536 patients. Within 2 years, 18.3% experienced a switch among patients receiving combination therapy and 24.8% in patients treated with infliximab alone, corresponding to an adjusted HR of 0.66 [95% CI 0.45–0.97] in patients receiving combination therapy. Conclusions The HR of intestinal surgeries and the risk of a switch to another anti-TNFα was reduced in paediatric and adolescent patients receiving combination therapy, compared to patients receiving only infliximab. These results suggest a benefit for infliximab therapy combined with immunomodulators, but these need to be confirmed in data with additional clinical information.

Characterization of calves exhibiting a novel inheritable TNF-α hyperresponsiveness to endotoxin: associations with increased pathophysiological complications

2005 ◽  
Vol 98 (6) ◽  
pp. 2045-2055 ◽  
Author(s):  
T. H. Elsasser ◽  
J. W. Blum ◽  
S. Kahl
Keyword(s):  
Mononuclear Cells ◽  
Acute Phase Protein ◽  
Peripheral Blood Mononuclear ◽  
Lps Challenge ◽  
Genetic Potential ◽  
Tnf Α ◽  
Related Stress

A subpopulation of calves, herein termed “hyperresponders” (HPR), was identified and defined by the patterns of plasma TNF-α concentrations that developed following two challenges with endotoxin (LPS, 0.8 μg Escherichia coli 055:B5 LPS/kg0.75live body wt) separated by 5 days. The principle characteristic of HPR calves was a failure to develop tolerance to repeated LPS challenge that was evident in the magnitude of the TNF-α concentrations and prolonged severity of pathological sequellae. Whereas calves failing to develop LPS tolerance were identified on the basis of their excessive in vivo plasma TNF-α concentration responses, in vitro TNF-α responses of peripheral blood mononuclear cells isolated from each calf and challenged with LPS or PMA did not correlate or predict the magnitude of in vivo plasma TNF response of the calf. Intentional breeding to obtain calves from bulls and/or cows documented as HPR resulted in offspring displaying the HPR character when similar progeny calves were tested with LPS in vivo, with extensive controls in place to account for sources of variability in the general TNF-α response to LPS that might compromise interpretation of the data. Feed intake, clinical serology and hematology profiles, and acute-phase protein responses of HPR calves following LPS were significantly different from those of calves displaying tolerance. These results suggest that the pattern of plasma TNF-α changes that evolve from a low-level double LPS challenge effectively reveal the presence of a genetic potential for animals to display excessive or prolonged pathological response to LPS-related stress and compromised prognosis for recovery.

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.

Monocyte Derivatives Promote Angiogenesis and Myocyte Survival in a Model of Myocardial Infarction

2010 ◽  
Vol 19 (4) ◽  
pp. 369-386 ◽  
Author(s):  
M. Bouchentouf ◽  
P. Paradis ◽  
K. A. Forner ◽  
J. Cuerquis ◽  
M. N. Boivin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Endothelial Cell ◽  
Mononuclear Cells ◽  
Endothelial Cell Proliferation ◽  
Blood Monocytes ◽  
Vascular Networks ◽  
Peripheral Blood Mononuclear ◽  
Mature Endothelial Cell ◽  
Tnf Α

In this study, we have investigated the hypothesis that previously reported beneficial effect of peripheral blood mononuclear cells cultured under angiogenic conditions on cardiovascular function following ischemia is not limited to EPCs but also to monocytes contained therein. We first purified and analyzed the phenotype and secretome of human and murine blood monocytes cultured under angiogenic conditions (named MDs for monocyte derivatives) and tested their effect in a mouse model of myocardial infarction (MI). FACS analysis of MDs shows that these cells express mature endothelial cell markers and that their proliferative capacity is virtually absent, consistent with their end-differentiated monocytic ontogeny. MDs secreted significant levels of HGF, IGF-1, MCP-1, and sTNFR-1 relative to their monocyte precursors. MDs were unable to form vascular networks in vitro when cultured on matrix coated flasks. Treatment of murine HL-1 cardiomyocyte cell line with MD-conditioned medium reduced their death induced by TNF-α, staurosporine, and oxidative stress, and this effect was dependent upon MD-derived sTNFR-1, HGF, and IGF-1. We further demonstrate that MD secretome promoted endothelial cell proliferation and capacity to form vessels in vitro and this was dependent upon MD-derived MCP-1, HGF, and IGF-1. Echocardiography analysis showed that MD myocardial implantation improved left ventricle fractional shortening of mouse hearts following MI and was associated with reduced myocardial fibrosis and enhancement of angiogenesis. Transplanted MDs and their secretome participate in preserving functional myocardium after ischemic insult and attenuate pathological remodeling.

scholarly journals The effect of marine oil-derived n-3 fatty acids on transepithelial calcium transport in Caco-2 cell models of healthy and inflamed intestines

2007 ◽  
Vol 97 (2) ◽  
pp. 281-288 ◽  
Author(s):  
Jennifer Gilman ◽  
Kevin D. Cashman
Keyword(s):  
Fatty Acids ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Human Subjects ◽  
Healthy Human ◽  
Marine Oil ◽  
Ca Transport ◽  
Tnf Α

Marine oil-derived n-3 fatty acids have been shown to stimulate intestinal Ca absorption in animal studies, but the effects of such fatty acids on Ca absorption in human subjects are relatively unknown. In particular, n-3 fatty acids may be of therapeutic value for some Crohn's disease patients who experience Ca malabsorption. Therefore, the aim of the present study was to investigate the effect of 20 : 5n-3 and 22 : 6n-3 on transepithelial Ca transport across monolayers of healthy Caco-2 cells as well as of TNF-α-treated Caco-2 cells (an in vitro model of Crohn's disease). Caco-2 cells were seeded onto permeable filter supports and allowed to differentiate into monolayers, which were treated with 80 μm-20 : 5n-3, 80 μm-22 : 6n-3, or 40 μm-20 : 5n-3+40 μm-22 : 6n-3 for 6 or 8 d, with or without co-treatment with TNF-α (10 ng/ml) (n 11–15 monolayers per treatment). On day 16, transepithelial and transcellular transport of 45Ca and fluorescein transport (a marker of paracellular diffusion) were measured. Treatment of healthy and inflamed Caco-2 cells with 20 : 5n-3, 22 : 6n-3 and both fatty acids combined for 8 d significantly (P < 0·005–0·01) increased total transepithelial Ca transport compared with that in control, effects which were mediated by an enhanced rate of transcellular Ca transport. The effects of n-3 fatty acids on Ca absorption after 6 d were less clear-cut. In conclusion, the present in vitro findings highlight the need to investigate the effect of marine oil-based n-3 fatty acids on Ca absorption in vivo in studies of healthy human subjects as well as of Crohn's disease patients.

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