Functional characterisation of decoy receptor 3 in Crohn's disease

Funke, Benjamin; Autschbach, Frank; Kim, Sunghee; Lasitschka, Felix; Strauch, Ulrike; Rogler, Gerhard; Gdynia, Georg; Li, Li; Gretz, Norbert; Macher-Goeppinger, Stephan; Sido, Bernd; Schirmacher, Peter; Meuer, Stefan; Roth, Wilfried

doi:10.1136/gut.2008.148908

Cited by 58 publications

(44 citation statements)

References 37 publications

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“…Recent studies have demonstrated that inflammation is a key factor in the induction of DcR3 expression, which was observed in epithelial cells in acute appendicitis (25) or Crohn's disease (26). In our study, DcR3 was expressed only in lymphatic tumor cells and squamous metaplastic tumor cells but not in macrophages and CPTC.…”

Section: Discussionsupporting

confidence: 47%

Expression of Decoy Receptor 3 in Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma: Correlation with M2 Macrophage Differentiation and Lymphatic Invasion

Chang

Chen

Lee

et al. 2013

Thyroid

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Background: The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is a unique variant of PTC that is characterized by extensive lymphovascular invasion of tumor cells in a background of lymphocytic thyroiditis. The lymphatic emboli contain tumor cells as well as macrophages, but the recruitment of these macrophages is not well understood. The aim of this study was to determine the relationship between the expression of Decoy receptor 3 (DcR3), the recruitment of tumor-associated macrophages (TAMs), and lymphatic invasion in DSV-PTC. Methods: We retrospectively examined 14 cases of DSV-PTC using immunohistochemistry studies. The density of TAMs, lymphatic vessel density, lymphatic invasion, tumor emboli area, and DcR3 expression were assessed. Statistical analyses were performed using Fisher's exact test, unpaired t-test, and linear regression. Results: The lymphatic tumor emboli contained a relatively higher density of TAMs than stroma and classical PTC (CPTC) areas. In addition, the number of lymphatic invasions and the size of the tumor emboli area were positively correlated with the number of M2 TAMs. A higher density of M2 TAMs was associated with older patients and larger tumor size. Moreover, DcR3 was expressed only in lymphatic tumor cells and squamous metaplastic tumor cells, but not in macrophages and CPTC. In addition, the preferential expression of DcR3 in tumors was associated with higher levels of M2 TAMs and lymphatic invasion. Conclusion: Despite the fact that the exact relationship between DcR3, M2 macrophages, and lymphatic invasion in DSV-PTC remains to be elucidated, our findings suggest that DcR3 expression in DSV-PTC tumor cells may promote the polarized macrophage differentiation toward the M2 phenotype. This phenomenon may further promote lymphatic invasion of DSV-PTC tumor cells.

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Section: Discussionsupporting

confidence: 47%

Expression of Decoy Receptor 3 in Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma: Correlation with M2 Macrophage Differentiation and Lymphatic Invasion

Chang

Chen

Lee

et al. 2013

Thyroid

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“…A subset of frozen samples was cut into 18 mm thick sections using a cryostat (Leica CM1850; Leica Microsystems, Wetzlar, Germany) and was processed by laser microdissection and pressure catapulting using a Microbeam LMPC System (Carl Zeiss MicroImaging, Jena, Germany) as described. 44 DNA was isolated using the Puregene Tissue Core Kit B (Qiagen, Hilden, Germany) according to manufacturer's instructions.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic screen of human DNA repair genes identifies aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma

et al. 2012

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Aberrant promoter methylation of different DNA repair genes has a critical role in the development and progression of various cancer types, including head and neck squamous cell carcinomas (HNSCCs). A systematic analysis of known human repair genes for promoter methylation is however missing. We generated quantitative promoter methylation profiles in single CpG units of 160 human DNA repair genes in a set of DNAs isolated from fresh frozen HNSCC and normal tissues using MassARRAY technology. Ninety-eight percent of these genes contained CpG islands (CGIs) in their promoter region; thus, DNA methylation is a potential regulatory mechanism. Methylation data were obtained for 145 genes, from which 15 genes exhibited more than a 20% difference in methylation levels between tumor and normal tissues, manifested either as hypermethylation or as hypomethylation. Analyses of promoter methylation with mRNA expression identified the DNA glycosylase NEIL1 (nei endonuclease VIII-like 1) as the most prominent candidate gene. NEIL1 promoter hypermethylation was confirmed in additional fresh frozen HNSCC samples, normal mucosa, HNSCC cell lines and primary human skin keratinocytes. The investigation of laser-microdissected tissues further substantiated increased methylation levels in tumor versus matched non-tumor cells. Immunohistological analysis revealed significantly less NEIL1 protein expression in tumor tissues. 5-Aza-2 0 -deoxycytidine treatment and DNMT1 knockdown resulted in the re-expression of NEIL1 in HNSCC cell lines, which initially carried hypermethylated promoter regions. In conclusion, our results suggest that DNA methylation contributes to the downregulation of NEIL1 expression and might thus have a role in modulating the response to therapies of HNSCC.

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“…Researchers demonstrated that DcR3 modulated macrophage activation toward an M2-like phenotype in vitro and downregulated MHC class II expression in tumor-associated macrophages via epigenetic control, which made it difficult to clear the virus (Tai et al 2012). DcR3 is able to elicit the secretion of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and IL-8 from endothelial cells , as well as promoting inflammation in Crohn disease partly by inducing NF-κB activation (Funke et al 2009). …”

Section: Discussionmentioning

confidence: 99%

Serum Decoy Receptor 3 Is a Useful Predictor for the Active Status of Chronic Hepatitis B in Hepatitis B e Antigen-Negative Patients

Hou

Lou

et al. 2013

Tohoku J. Exp. Med.

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Hepatitis B virus (HBV) infection is a global public health problem, because patients with chronic hepatitis B (CHB) may progress to liver cirrhosis and eventually evolve into hepatocellular carcinoma. Decoy receptor 3 (DcR3) is a soluble receptor of the tumor necrosis factor receptor superfamily, and has been implicated in anti-apoptotic and anti-inflammatory pathways. In this study, we explored the clinical value of serum DcR3 in predicting the active status of CHB in hepatitis B e antigen-negative patients (active HBeAg (−) CHB), which was determined with ELISA. The serum level of DcR3 in active HBeAg (−) CHB patients (1.92 ± 0.68 ng/ml) was higher than that in healthy controls (0.80 ± 0.25 ng/ml, p < 0.0001) and that in inactive status of HBeAg (−) CHB (inactive hepatitis B surface antigen carrier, HBsAg-IaC) patients (0.95 ± 0.26 ng/ml, p < 0.0001). DcR3 level was correlated with HBV DNA level (r = 0.819, p < 0.0001) and alanine transaminase level (ALT, r = 0.704, p < 0.0001) in active HBeAg (−) CHB patients. The area under the Receiver Operating Characteristics curve of DcR3 for detecting the active status of HBeAg (−) CHB patients was 0.914 (95% confidence interval, 0.851-0.977). The optimal cut-off value for DcR3 to predict active HBeAg (−) CHB was 1.22 ng/ml, which had a sensitivity of 87.5% and a specificity of 84.4%. These results suggest that serum DcR3 level may be useful for detecting HBeAg (−) CHB in the active stage, which requires medical treatment.

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Functional characterisation of decoy receptor 3 in Crohn's disease

Cited by 58 publications

References 37 publications

Expression of Decoy Receptor 3 in Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma: Correlation with M2 Macrophage Differentiation and Lymphatic Invasion

Expression of Decoy Receptor 3 in Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma: Correlation with M2 Macrophage Differentiation and Lymphatic Invasion

Epigenetic screen of human DNA repair genes identifies aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma

Serum Decoy Receptor 3 Is a Useful Predictor for the Active Status of Chronic Hepatitis B in Hepatitis B e Antigen-Negative Patients

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