scholarly journals Expression profiling of ileal mucosa in asthma reveals upregulation of innate immunity and genes characteristic of Paneth and goblet cells

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Jan K. Nowak ◽  
Marzena Dworacka ◽  
Nazgul Gubaj ◽  
Arystan Dossimov ◽  
Zhumabek Dossimov ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Differential Expression ◽  
Expression Profiles ◽  
Differential Expression Analysis ◽  
Goblet Cells ◽  
Ileal Mucosa ◽  
Significant Differential Expression ◽  
Immune Genes ◽  
Asthma Patients

Abstract Background The expression profiles of the intestinal mucosa have not been comprehensively investigated in asthma. We aimed to explore this in the Correlated Expression and Disease Association Research (CEDAR) patient cohort. Methods Differential expression analysis of ileal, transverse colon, and rectal biopsies were supplemented by a comparison of transcriptomes from platelets and leukocytes subsets, including CD4+, CD8+, CD14+, CD15+, and CD19+ cells. Asthma patients (n = 15) and controls (n = 15) had similar age (p = 0.967), body mass index (p = 0.870), similar numbers of females (80%) and smoking rates (13.3%). Results Significant differential expression was found in the ileum alone, and not in any other cell/tissue types. More genes were found to be overexpressed (1,150) than under-expressed (380). The most overexpressed genes included Fc Fragment of IgG Binding Protein (FCGBP, logFC = 3.01, pFDR = 0.015), Mucin 2 (MUC2, logFC = 2.78, pFDR = 0.015), and Alpha 1B Defensin (DEFA1B, logFC = 2.73, pFDR = 0.024). Gene ontology implicated the immune system, including interleukins 4 and 13, as well as antimicrobial peptides in this overexpression. There was concordance of gene over- (STAT1, XBP1) and underexpression (NELF, RARA) in asthma and Crohn’s disease ileum when our results were compared to another dataset (p = 3.66 × 10–7). Conclusion Ileal mucosa in asthma exhibits a specific transcriptomic profile, which includes the overexpression of innate immune genes, mostly characteristic of Paneth and goblet cells, in addition to other changes that may resemble Crohn’s disease.

scholarly journals Tu1932 Differential Expression of MicroRNAs in Ileal Mucosa of Patients With Early, Recurrent and Late Crohn's Disease

2014 ◽  
Vol 146 (5) ◽  
pp. S-875-S-876
Author(s):  
Jan Van der Goten ◽  
Ingrid Arijs ◽  
Leentje Van Lommel ◽  
Sophie Organe ◽  
Wiebe Vanhove ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Differential Expression ◽  
Ileal Mucosa

Diving into inflammation: a pilot study exploring the dynamics of the immune-microbiota axis in ileal tissue layers of patients with Crohn’s disease

2021 ◽  
Author(s):  
Edda Russo ◽  
Francesco Giudici ◽  
Federica Ricci ◽  
Stefano Scaringi ◽  
Giulia Nannini ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Tissue Injury ◽  
Microbiota Composition ◽  
Response Distribution ◽  
Ileal Mucosa ◽  
The Family ◽  
New Biomarkers ◽  
Clinical Conditions ◽  
Ileal Tissue

Abstract Background and aims Crohn’s Disease (CD) pathogenesis is still unclear. Disorders in the mucosal immunoregulation and its crosstalk with the microbiota may represent an important component in tissue injury. We aimed to characterize the molecular immune response distribution within the ileal layers and to evaluate the correlated microbiota in pathological/healthy settings comparing first surgery/relapse clinical conditions. Methods We enrolled 12 CD patients. A comprehensive analysis of ileal mucosa, submucosa and serosa broad-spectrum cytokines’ panel was performed through a multiplex approach. In addition, ileal microbiota composition was assessed through Next Generation Sequencing. Results We observed a distinct profile (of IL1-α, IL-1β, IL-4, IL-8, ICAM-1, E-Selectin, P-Selectin, IP-10, IL 6, and IL 18) across the CD vs healthy ileal layers; and a different distribution of IFN-γ, P-Selectin, IL-27 and IL-21 in first surgery vs relapse patients. In addition, the phylum Tenericutes, the family of Ruminococcaceae, and the genus Mesoplasma and Mycoplasma were significantly enriched in pathological setting. Significant microbiota differences were observed between relapse vs first surgery patients regarding the class Bacteroidia, the genus of Prevotella, Flavobacterium, Tepidimonas and Escherichia/Shigella. Finally, the abundance of the genus Mycoplasma was positively correlated with IL-18. Conclusions We describe a dissimilarity of cytokines’ distribution and microbiota composition within the CD and the adjacent healthy ileal tissue layers and between first operation and surgical relapse. Our results give a potential insight into the dynamics of the gut microbiota-immune axis in CD patients, leading to new biomarkers’ detection.

scholarly journals Thyrotroph embryonic factor (TEF) is differentially expressed in high-grade serous ovarian cancers.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Ovarian Cancer ◽  
Transcription Factor ◽  
Differential Expression ◽  
Expression Profiles ◽  
Gynecologic Cancer ◽  
Bzip Transcription Factor ◽  
High Grade ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
Embryonic Factor

Ovarian cancer is the most lethal gynecologic cancer (1). We sought to identify genes associated with high-grade serous ovarian cancer (HGSC) by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with HGSC using published microarray data (2, 3). We previously reported differential expression of the PAR-bZIP transcription factor HLF in HGSC (4). Here, we report significant differential expression of a second PAR-bZIP transcription factor, thyrotroph embryonic factor (TEF) (5) in high-grade serous ovarian tumors.

Abstract WP120: MicroRNA Expression in Patients With Acute Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Janhavi M Modak ◽  
Meaghan A Roy-O’Reilly ◽  
Sarah E Conway ◽  
Liang Zhu ◽  
Louise D McCullough
Keyword(s):  
Ischemic Stroke ◽  
Differential Expression ◽  
Expression Profiles ◽  
Outpatient Setting ◽  
Microrna Expression ◽  
Neurological Deficits ◽  
Stroke Patients ◽  
Significant Differential Expression ◽  
Blood Samples ◽  
Mrna Targets

Background and Purpose: MicroRNAs (miRNAs) are a class of endogenous small non-coding ribonucleic acids that regulate gene expression and can impact cellular function by suppressing or activating downstream mRNA targets. Pre-clinical studies in animal models of stroke have demonstrated specific changes in miRNA expression profiles after ischemic stroke. Methods: Patients admitted to Hartford Hospital from January 2011 - March 2014 were considered for this study. Blood samples were collected within 24 hours of stroke presentation. miRNA profiles from peripheral blood samples of ischemic stroke patients were compared to controls. Patients with acute middle cerebral artery (MCA) cardioembolic strokes (based on TOAST criteria) were included (n=16). Blood collected from patients with no acute neurological deficits in an outpatient setting served as controls (n=8). Individuals with a history of active cancer, neoplastic brain lesions or traumatic brain injury were excluded. Based on literature review, 173 miRNAs were selected to assess for differential expression between cases and controls. miRNA profiling was conducted at Exiqon Services, Denmark, using miRCURY LNA™ microRNA Array. Statistical analysis was performed using SAS. Results: In patients with acute ischemic strokes, a statistically significant differential expression was observed in 14 miRNAs as compared to controls. MicroRNAs miR-1273e, miR-5187-3p were found to be downregulated in stroke patients (p=0.01). Other miRNAs showing a significant downregulation included let 7e-5p (p=0.03); miR-4709-3p, miR-4756-3p, miR-5584-3p, miR-647 (p=0.02); miR-4742-3p (p=0.03); miR-4764-5p, miR-4531 and miR-2116-5p (p=0.04). MicroRNAs miR-664a-3p (p=0.02), miR-943 (p=0.04) and miR-145-5p (p=0.03) were significantly upregulated. Differential expression in males and females was not observed. Conclusion: Ischemic stroke patients show a differential microRNA expression profile as compared to controls. Further studies can help identify microRNA signatures as well as the downstream targets involved in the ischemic stroke molecular cascade.

scholarly journals De novo assembly of the Brown trout (Salmo trutta m. fario) brain and muscle transcriptome: transcript annotation, tissue differential expression profile and SNP discovery

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
J. Fibla ◽  
N. Oromi ◽  
M. Pascual-Pons ◽  
J. L. Royo ◽  
A. Palau ◽  
...  
Keyword(s):  
Differential Expression ◽  
Brown Trout ◽  
Salmo Trutta ◽  
De Novo ◽  
Transcriptome Assembly ◽  
Differential Expression Analysis ◽  
Cdna Libraries ◽  
Significant Differential Expression ◽  
Reference Transcriptome ◽  
Salmonid Species

Abstract Objectives The Brown trout is a salmonid species with a high commercial value in Europe. Life history and spawning behaviour include resident (Salmo trutta m. fario) and migratory (Salmo trutta m. trutta) ecotypes. The main objective is to apply RNA-seq technology in order to obtain a reference transcriptome of two key tissues, brain and muscle, of the riverine trout Salmo trutta m. fario. Having a reference transcriptome of the resident form will complement genomic resources of salmonid species. Data description We generate two cDNA libraries from pooled RNA samples, isolated from muscle and brain tissues of adult individuals of Salmo trutta m. fario, which were sequenced by Illumina technology. Raw reads were subjected to de-novo transcriptome assembly using Trinity, and coding regions were predicted by TransDecoder. A final set of 35,049 non-redundant ORF unigenes were annotated. Tissue differential expression analysis was evaluated by Cuffdiff. A False Discovery Rate (FDR) ≤ 0.01 was considered for significant differential expression, allowing to identify key differentially expressed unigenes. Finally, we have identified SNP variants that will be useful tools for population genomic studies.

scholarly journals Invasive Ability of an Escherichia coliStrain Isolated from the Ileal Mucosa of a Patient with Crohn’s Disease

1999 ◽  
Vol 67 (9) ◽  
pp. 4499-4509 ◽  
Author(s):  
Jerome Boudeau ◽  
Anne-Lise Glasser ◽  
Estelle Masseret ◽  
Bernard Joly ◽  
Arlette Darfeuille-Michaud
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Host Cell ◽  
Bacterial Invasion ◽  
Intestinal Epithelial ◽  
Invasive Ability ◽  
Ileal Mucosa ◽  
Gastrointestinal Infections ◽  
E Coli ◽  
Host Cell Membranes

ABSTRACT Crohn’s disease (CD) is an inflammatory bowel disease in whichEscherichia coli strains have been suspected of being involved. We demonstrated previously that ileal lesions of CD are colonized by E. coli strains able to adhere to intestinal Caco-2 cells but devoid of the virulence genes so far described in the pathogenic E. coli strains involved in gastrointestinal infections. In the present study we compared the invasive ability of one of these strains isolated from an ileal biopsy of a patient with CD, strain LF82, with that of reference enteroinvasive (EIEC), enteropathogenic (EPEC), enterotoxigenic (ETEC), enteraggregative (EAggEC), enterohemorrhagic (EHEC), and diffusely adhering (DAEC)E. coli strains. Gentamicin protection assays showed thatE. coli LF82 was able to efficiently invade HEp-2 cells. Its invasive level was not significantly different from that of EIEC and EPEC strains (P > 0.5) but significantly higher than that of ETEC (P < 0.03), EHEC (P < 0.005), EAggEC (P < 0.004) and DAEC (P < 0.02) strains. Strain LF82 also demonstrated efficient ability to invade intestinal epithelial cultured Caco-2, Intestine-407, and HCT-8 cells. Electron microscopy examination of infected HEp-2 cells revealed the presence of numerous intracellular bacteria located in vacuoles or free in the host cell cytoplasm. In addition, the interaction of strain LF82 with epithelial cells was associated with the elongation of microvillar extensions that extruded from the host cell membranes and engulfed the bacteria. This internalization mechanism strongly resembles Salmonella- orShigella-induced macropinocytosis. The use of cytochalasin D and colchicine showed that the uptake of strain LF82 by HEp-2 cells was mediated by both an actin microfilament-dependent mechanism and microtubule involvement. In addition, strain LF82 survived for at least 24 h in HEp-2 and Intestine-407 cells and efficiently replicated intracellularly in HEp-2 cells. PCR and hybridization experiments did not reveal the presence of any of the genetic determinants encoding EIEC, EPEC, or ETEC proteins involved in bacterial invasion. Thus, these findings show that LF82, which colonized the ileal mucosa of a patient with CD, is a true invasive E. coli strain and suggest the existence of a new potentially pathogenic group of E. coli, which we propose be designated adherent-invasive E. coli.

scholarly journals DOP06 Non-invasive identification of adherent-invasive E. coli in patients with Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S044-S045 ◽  
Author(s):  
A Buisson ◽  
E Vazeille ◽  
X Hébuterne ◽  
M Fumery ◽  
B Pariente ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Unmet Need ◽  
Inhibition Test ◽  
Invasive Ability ◽  
Ileal Mucosa ◽  
Multi Centre Study ◽  
E Coli ◽  
Non Invasive ◽  
Adhesion Inhibition

Abstract Background Medications limiting the adhesion of ‘adherent and invasive E. coli’ (AIEC) represent potential strategies to treat Crohn’s disease (CD). However, the ileal AIEC identification is a time-consuming procedure, and the number of AIEC strains which colonise ileal CD mucosa remains unknown. There is an unmet need for non-invasive biomarkers to identify patients colonised by AIEC. We aimed to evaluate non-invasive biomarker of ileal AIEC colonisation in patients with CD. Methods This prospective and multi-centre study included CD patients requiring ileocoloscopy. Saliva, serum, stools and ileal biopsies were collected. Abundance and global invasive ability of ileal or faecal E. coli were performed. Isolated E. coli were characterised as AIEC or non-AIEC on I407 epithelial cells and THP1 macrophages. The ERIC-PCR profiles of ileal E. coli were performed. Ileal E. coli/CEACAM6 interaction was analysed by a yeast aggregation test and T84 assays (CEACAM6 protein expression, adhesion inhibition test with D-mannose). Quantification of serum anti-E. coli and ileal or salivary CEACAM6 was realised by ELISA. Results Overall, 102 CD patients were enrolled in this study and 25.8% of them exhibited ileal AIEC colonisation (AIEC+). The abundance and global invasive ability of ileal mucosa-associated E. coli were higher in AIEC+ CD patients compared with CD patients without AIEC (AIEC−) (p = 0.0065 and p = 0.0007, respectively). There was no difference between faecal abundance and invasive ability of E. coli between AIEC+ and AIEC− patients. The ERIC-PCR profiles of ileal E. coli showed that CD AIEC+ were for 78% of them colonised by not more than 2 clonal AIEC strains. In addition, AIEC were able to interact with CEACAM6 by binding D-mannose residues and to induce CEACAM6 expression in T84 cells (p = 0.0009 and p = 0.0185, vs. non-AIEC; respectively). This was also supported by adhesion inhibition test. Serum anti-E. coli level was higher for CD AIEC+ (vs. CD AIEC-). Ileal CEACAM6 level were positively correlated with abundance of ileal associated E. coli in AIEC+ patients (r = 0.4000; p = 0.0362) and with salivary CEACAM6 level (r = 0.4690; p &lt; 0.0001). The non-invasive biomarker ‘serum anti-E.coli/salivary CEACAM6’ index was higher for CD AIEC+ (p = 0.0174; vs. CD AIEC-). A cut-off value &lt; 1.34 × 10−6 eliminated the presence of ileal AIEC with a high negative predictive value (90% CI95% [69%–95%]). Conclusion Our study reported that identification of faecal AIEC cannot replace identification of AIEC from ileal biopsies, most of AIEC infection are mono or bi-clonal (≤ 2 strains) and that non-invasive biomarker such as ‘serum anti-E.coli/salivary CEACAM6’ index could be helpful to screen CD patients for AIEC infection.

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