Patterns of mucosal inflammation in pediatric inflammatory bowel disease: striking overexpression of IL-17A in children with ulcerative colitis

Busch, Meike A; Gröndahl, Britta; Knoll, Rebecca Luise; Pretsch, Leah; Doganci, Aysefa; Hoffmann, Isabell; Kullmer, Ulrike; Bähner, Viola; Zepp, Fred; Meyer, Claudius U.; Gehring, Stephan

doi:10.1038/s41390-019-0486-5

Cited by 10 publications

(5 citation statements)

References 36 publications

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“…Consequently, it can lead to an increase in the accumulation of the drug in the inflamed areas of the colon. In the period of inflammation, the overexpression of inflammatory biomarkers is an important pathophysiological change ( Liu et al, 2019 ; Busch et al, 2020 ; Yin et al, 2020 ). For example, the overexpression of glycoprotein CD98 is occurred in the inflamed colon ( Guo et al, 2016 ; Rahiman et al, 2022 ).…”

Section: Targeting Pathophysiological Changes Using Biomaterials-base...mentioning

confidence: 99%

Targeting pathophysiological changes using biomaterials-based drug delivery systems: A key to managing inflammatory bowel disease

et al. 2022

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Inflammatory bowel disease (IBD) is a gastrointestinal disorder, affecting about several million people worldwide. Current treatments fail to adequately control some clinical symptoms in IBD patients, which can adversely impact the patient’s quality of life. Hence, the development of new treatments for IBD is needed. Due to their unique properties such as biocompatibility and sustained release of a drug, biomaterials-based drug delivery systems can be regarded as promising candidates for IBD treatment. It is noteworthy that considering the pathophysiological changes occurred in the gastrointestinal tract of IBD patients, especially changes in pH, surface charge, the concentration of reactive oxygen species, and the expression of some biomolecules at the inflamed colon, can help in the rational design of biomaterials-based drug delivery systems for efficient management of IBD. Here, we discuss about targeting these pathophysiological changes using biomaterials-based drug delivery systems, which can provide important clues to establish a strategic roadmap for future studies.

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Section: Targeting Pathophysiological Changes Using Biomaterials-base...mentioning

confidence: 99%

Targeting pathophysiological changes using biomaterials-based drug delivery systems: A key to managing inflammatory bowel disease

et al. 2022

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“…Ulcerative colitis (UC) is a chronic inflammatory disease of the colon [ 1 , 2 ]. Damage to the intestinal barrier is driven by numerous infiltrating immune cells and alerted cytokine networks, with the important involvement of both innate and adaptive immune responses [ 3 , 4 ]. The inflamed gut mucosa hosts plenty of activated lymphocytes (T helper 2, T helper 1, regulatory T subsets), antigen-presenting cells (dendritic cells and macrophages), and natural killers [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Insufficient suppression of inflammation in UC is characterized by the synthesis of Th2-type cytokines and interferon-gamma (IFN-γ). These further aggravate the imbalance between pro- (IL-1, 6, 9, 13, 33, and TNF-α) and anti-inflammatory (IL-10, 37, and TGF-β) cytokines [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Methylation of RUNX3 Promoter 2 in the Whole Blood of Children with Ulcerative Colitis

Dybska

Nowak

Banaszkiewicz

et al. 2022

Genes

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Ulcerative colitis (UC) results from a complex interplay between the environment, gut microbiota, host genetics, and immunity. Runt-related transcription factor 3 (RUNX3) regulates Th1/Th2 balance and, thus, the synthesis of cytokines and inflammation. We aimed to analyze the dependence of RUNX3 promoter 2 (P2) methylation level on: age, sex, body mass index (BMI), C-reactive protein (CRP), serum albumin, disease duration, Pediatric Ulcerative Colitis Activity Index (PUCAI), the Paris classification, and exposure to medications. This multicenter, cross-sectional study recruited hospitalized children with UC. Methylation of RUNX3 P2 was measured with methylation-sensitive restriction enzymes in the whole blood DNA. Sixty-four children were enrolled, with a mean age of 14.5 ± 2.8 years. Half of them were female (51.6%), and the average BMI Z-score was −0.44 ± 1.14. The mean methylation of RUNX3 P2 was 54.1 ± 13.3%. The methylation level of RUNX3 P2 did not correlate with age, sex, nutritional status, CRP, albumin, PUCAI, or the extent of colitis (Paris E1–E4). RUNX3 P2 methylation did not differ between patients recruited within two and a half months of diagnosis and children who had UC for at least a year. Current or past exposure to biologics, immunosuppressants, or steroids was not associated with RUNX3 P2 methylation. Methylation of RUNX3 promoter 2 in whole blood DNA does not seem to be associated with the characteristics of UC in children.

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“…An important reason for difficulties in finding biomarkers is indicated by expression profiling studies of whole blood cells (WBC) and colon biopsies, which have identified hundreds of disease-associated genes [11][12][13][14]. A similar complexity has been found in other pediatric diseases [15].…”

Section: Introductionmentioning

confidence: 99%

Meta-Analysis of Expression Profiling Data Indicates Need for Combinatorial Biomarkers in Pediatric Ulcerative Colitis

Lee

Gawel

et al. 2020

Journal of Immunology Research

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Background. Unbiased studies using different genome-wide methods have identified a great number of candidate biomarkers for diagnosis and treatment response in pediatric ulcerative colitis (UC). However, clinical translation has been proven difficult. Here, we hypothesized that one reason could be differences between inflammatory responses in an inflamed gut and in peripheral blood cells. Methods. We performed meta-analysis of gene expression microarray data from intestinal biopsies and whole blood cells (WBC) from pediatric patients with UC and healthy controls in order to identify overlapping pathways, predicted upstream regulators, and potential biomarkers. Results. Analyses of profiling datasets from colonic biopsies showed good agreement between different studies regarding pathways and predicted upstream regulators. The most activated predicted upstream regulators included TNF, which is known to have a key pathogenic and therapeutic role in pediatric UC. Despite this, the expression levels of TNF were increased in neither colonic biopsies nor WBC. A potential explanation was increased expression of TNFR2, one of the membrane-bound receptors of TNF in the inflamed colon. Further analyses showed a similar pattern of complex relations between the expression levels of the regulators and their receptors. We also found limited overlap between pathways and predicted upstream regulators in colonic biopsies and WBC. An extended search including all differentially expressed genes that overlapped between colonic biopsies and WBC only resulted in identification of three potential biomarkers involved in the regulation of intestinal inflammation. However, two had been previously proposed in adult inflammatory bowel diseases (IBD), namely, MMP9 and PROK2. Conclusions. Our findings indicate that biomarker identification in pediatric UC is complicated by the involvement of multiple pathways, each of which includes many different types of genes in the blood or inflamed intestine. Therefore, further studies for identification of combinatorial biomarkers are warranted. Our study may provide candidate biomarkers for such studies.

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Patterns of mucosal inflammation in pediatric inflammatory bowel disease: striking overexpression of IL-17A in children with ulcerative colitis

Cited by 10 publications

References 36 publications

Targeting pathophysiological changes using biomaterials-based drug delivery systems: A key to managing inflammatory bowel disease

Targeting pathophysiological changes using biomaterials-based drug delivery systems: A key to managing inflammatory bowel disease

Methylation of RUNX3 Promoter 2 in the Whole Blood of Children with Ulcerative Colitis

Meta-Analysis of Expression Profiling Data Indicates Need for Combinatorial Biomarkers in Pediatric Ulcerative Colitis

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