scholarly journals Proteomic characterisations of ulcerative colitis endoscopic biopsies associate with clinically relevant histological measurements of disease severity

2021 ◽  
pp. jclinpath-2021-207718
Author(s):  
Aaron M Gruver ◽  
Matt D Westfall ◽  
Bradley L Ackermann ◽  
Salisha Hill ◽  
Ryan D Morrison ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Accuracy Assessment ◽  
Interleukin 2 ◽  
Proteome Analysis ◽  
Scoring Systems ◽  
Cell Junction ◽  
Interleukin 17 ◽  
Gamma Chain ◽  
Novel Approach ◽  
Interleukin 23

Aims and methodsAccurate protein measurements using formalin-fixed biopsies are needed to improve disease characterisation. This feasibility study used targeted and global mass spectrometry (MS) to interrogate a spectrum of disease severities using 19 ulcerative colitis (UC) biopsies.ResultsTargeted assays for CD8, CD19, CD132 (interleukin-2 receptor subunit gamma/common cytokine receptor gamma chain), FOXP3 (forkhead box P3) and IL17RA (interleukin 17 receptor A) were successful; however, assays for IL17A (interleukin 17A), IL23 (p19) (interleukin 23, alpha subunit p19) and IL23R (interleukin 23 receptor) did not permit target detection. Global proteome analysis (4200 total proteins) was performed to identify pathways associated with UC progression. Positive correlation was observed between histological scores indicating active colitis and neutrophil-related measurements (R2=0.42–0.72); inverse relationships were detected with cell junction targets (R2=0.49–0.71) and β-catenin (R2=0.51–0.55) attributed to crypt disruption. An exploratory accuracy assessment with Geboes Score and Robarts Histopathology Index cut-offs produced sensitivities/specificities of 72.7%/75.0% and 100.0%/81.8%, respectively.ConclusionsPathologist-guided MS assessments provide a complementary approach to histological scoring systems. Additional studies are indicated to verify the utility of this novel approach.

The interleukin-23/interleukin-17 immune axis as a promising new target in the treatment of spondyloarthritis

2014 ◽  
Vol 26 (4) ◽  
pp. 361-370 ◽  
Author(s):  
Nataliya Yeremenko ◽  
Jacqueline E. Paramarta ◽  
Dominique Baeten
Keyword(s):  
Interleukin 17 ◽  
Interleukin 23

Serum interleukin 17, interleukin 23, and interleukin 10 values in children with atopic eczema/dermatitis syndrome (AEDS): Association with clinical severity and phenotype

2015 ◽  
Vol 36 (1) ◽  
pp. 74-81 ◽  
Author(s):  
Salvatore Leonardi ◽  
Caterina Cuppari ◽  
Sara Manti ◽  
Martina Filippelli ◽  
Giuseppe Fabio Parisi ◽  
...  
Keyword(s):  
Atopic Eczema ◽  
Interleukin 10 ◽  
Clinical Severity ◽  
Interleukin 17 ◽  
Interleukin 23

Effects of supplemental dietary arginine on the exogenous advanced glycosylation end product–induced interleukin-23/interleukin-17 immune response in rats

Nutrition ◽  
2012 ◽  
Vol 28 (10) ◽  
pp. 1063-1067 ◽  
Author(s):  
Chiu-Li Yeh ◽  
Ya-Mei Hu ◽  
Jun-Jen Liu ◽  
Wei-Jao Chen ◽  
Sung-Ling Yeh
Keyword(s):  
Immune Response ◽  
Interleukin 17 ◽  
Interleukin 23 ◽  
Advanced Glycosylation

Interleukin-15 signals T84 colonic epithelial cells in the absence of the interleukin-2 receptor beta-chain

1997 ◽  
Vol 272 (5) ◽  
pp. G1201-G1208 ◽  
Author(s):  
A. C. Stevens ◽  
J. Matthews ◽  
P. Andres ◽  
V. Baffis ◽  
X. X. Zheng ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Interleukin 2 ◽  
Receptor Protein ◽  
Beta Chain ◽  
Gamma Chain ◽  
T84 Cells ◽  
Colonic Epithelial Cells ◽  
Common Gamma Chain ◽  
Interleukin 15 ◽  
The Common

Interleukin-15 (IL-15) shares many biological functions with interleukin-2 (IL-2) due to common receptor components. IL-15 binds to the IL-2 receptor (IL-2R) beta-chain and the common gamma-chain receptor in addition to one other IL-15 binding receptor protein (IL-15R alpha). Both IL-2R beta- and gamma-chains are required to promote cell growth in hematopoietic cells. The colonic cryptlike epithelial cell line T84 contains the common gamma-chain but lacks the IL-2R beta-chain. We report IL-15R alpha-chain mRNA in T84 cells with the use of reverse transcriptase-polymerase chain reaction. T84 and normal colonic epithelial cells bind a FLAG-IL-15 fusion protein in immunoperoxidase and flow cytometric experiments. In addition, IL-15, but not IL-2, accelerates and enhances the development of transepithelial resistance across T84 monolayers in a dose-dependent fashion. We conclude that normal and T84 colonic epithelial cells express IL-15R alpha and are able to bind IL-15. IL-15 can deliver a nonproliferative functional signal in the absence of IL-2R beta-chain in T84 cells.

scholarly journals Anti-interleukin-23 agents for the treatment of ulcerative colitis

2019 ◽  
Vol 20 (4) ◽  
pp. 399-406 ◽  
Author(s):  
Jurij Hanžel ◽  
Geert R. D’Haens
Keyword(s):  
Ulcerative Colitis ◽  
Interleukin 23

scholarly journals Identification of key genes and biological processes contributing to colitis associated dysplasia in ulcerative colitis

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11321
Author(s):  
Di Zhang ◽  
Pengguang Yan ◽  
Taotao Han ◽  
Xiaoyun Cheng ◽  
Jingnan Li
Keyword(s):  
Ulcerative Colitis ◽  
Mitochondrial Dysfunction ◽  
Single Gene ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Cell Junction ◽  
Biological Processes ◽  
Hub Genes ◽  
Key Genes

Background Ulcerative colitis-associated colorectal cancer (UC-CRC) is a life-threatening complication of ulcerative colitis (UC). The mechanisms underlying UC-CRC remain to be elucidated. The purpose of this study was to explore the key genes and biological processes contributing to colitis-associated dysplasia (CAD) or carcinogenesis in UC via database mining, thus offering opportunities for early prediction and intervention of UC-CRC. Methods Microarray datasets (GSE47908 and GSE87466) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between groups of GSE47908 were identified using the “limma” R package. Weighted gene co-expression network analysis (WGCNA) based on DEGs between the CAD and control groups was conducted subsequently. Functional enrichment analysis was performed, and hub genes of selected modules were identified using the “clusterProfiler” R package. Single-gene gene set enrichment analysis (GSEA) was conducted to predict significant biological processes and pathways associated with the specified gene. Results Six functional modules were identified based on 4929 DEGs. Green and blue modules were selected because of their consistent correlation with UC and CAD, and the highest correlation coefficient with the progress of UC-associated carcinogenesis. Functional enrichment analysis revealed that genes of these two modules were significantly enriched in biological processes, including mitochondrial dysfunction, cell-cell junction, and immune responses. However, GSEA based on differential expression analysis between sporadic colorectal cancer (CRC) and normal controls from The Cancer Genome Atlas (TCGA) indicated that mitochondrial dysfunction may not be the major carcinogenic mechanism underlying sporadic CRC. Thirteen hub genes (SLC25A3, ACO2, AIFM1, ATP5A1, DLD, TFE3, UQCRC1, ADIPOR2, SLC35D1, TOR1AIP1, PRR5L, ATOX1, and DTX3) were identified. Their expression trends were validated in UC patients of GSE87466, and their potential carcinogenic effects in UC were supported by their known functions and other relevant studies reported in the literature. Single-gene GSEA indicated that biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to angiogenesis and immune response were positively correlated with the upregulation of TFE3, whereas those related to mitochondrial function and energy metabolism were negatively correlated with the upregulation of TFE3. Conclusions Using WGCNA, this study found two gene modules that were significantly correlated with CAD, of which 13 hub genes were identified as the potential key genes. The critical biological processes in which the genes of these two modules were significantly enriched include mitochondrial dysfunction, cell-cell junction, and immune responses. TFE3, a transcription factor related to mitochondrial function and cancers, may play a central role in UC-associated carcinogenesis.

scholarly journals An interleukin-2 receptor gamma chain mutation with normal thymus morphology.

1997 ◽  
Vol 100 (12) ◽  
pp. 3036-3043 ◽  
Author(s):  
N Sharfe ◽  
M Shahar ◽  
C M Roifman
Keyword(s):  
Interleukin 2 ◽  
Gamma Chain ◽  
Interleukin 2 Receptor

Attenuation of IL-2-induced multisystem organ edema by phalloidin and antamanide

1991 ◽  
Vol 70 (3) ◽  
pp. 1364-1368 ◽  
Author(s):  
R. Welbourn ◽  
G. Goldman ◽  
L. Kobzik ◽  
C. R. Valeri ◽  
H. B. Hechtman ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Side Effects ◽  
Bronchoalveolar Lavage ◽  
Protein Concentration ◽  
Interleukin 2 ◽  
Cell Junction ◽  
Elevated Protein ◽  
Intravenous Saline

Interleukin 2 (IL-2) is a potent cytokine with diverse effects, including the ability to stimulate lymphocyte differentiation into cells capable of lysing tumor. Its therapeutic efficacy is limited because of side effects such as breakdown of the microvascular barrier and edema. Control of the microvascular barrier is in part regulated by endothelial cell cytoskeletal contractile proteins. This study tests whether the cyclopeptides that maintain actin filament organization and distribution and reduce macromolecular flux across the endothelial cell junction in vitro would similarly maintain barrier tightness and prevent early edema produced by IL-2 in vivo. Anesthetized rats were treated at 30-min periods with intravenous saline (0.5 ml, n = 41), phalloidin (20 micrograms in 0.5 ml, n = 21), or antamanide, (20 micrograms in 0.5 ml, n = 21), starting 30 min before the 1-h infusion of 10(6) U of recombinant human IL-2 or saline. Six hours after the start of IL-2, there was edema in the saline/IL-2 group, as measured by increased wet-to-dry ratios (W/D) in the lungs, heart, and kidney. With saline/IL-2, bronchoalveolar lavage (BAL) fluid contained an elevated protein concentration and higher plasma thromboxane levels compared with controls. The number of neutrophils sequestered in the lungs was more than twice that of saline controls. Phalloidin significantly attenuated edema in lung and reduced BAL protein leak. Antamanide treatment was as effective in limiting lung and heart edema, but, in contrast to phalloidin, antamanide prevented kidney edema and did not lead to an alteration in the liver W/D. Antamanide also prevented BAL fluid protein leak.(ABSTRACT TRUNCATED AT 250 WORDS)

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