Function and Regulation of Tumor Necrosis Factor Receptor Type 2

Despite the fact that accumulation of microglia, the resident macrophages of the central nervous system (CNS) are the main feature of glioblastoma, the role of microglia in the progression of glioma is still arguable. Based on the correlation of inflammation with tumor progression, in this study, we attempt to determine if peripheral inflammation aggravates glioma expansion and the activation of microglia associated with the tumor. Experimental animals were administered intraperitoneally by inflammagen lipopolysaccharide (LPS) for 7 days (LPS priming) before intracerebral implantation of glioma cells. Moreover, a reduced level of tumor necrosis factor receptor type 2 (TNFR2) that is restricted to immune cells, neurons, and microglia has been found in patients with glioblastoma through the clinic analysis of monocyte receptor expression. Thus, in addition to wildtype (WT) mice, heterogeneous TNFR2 gene deficiency (TNFR2+/−) mice and homogeneous TNFR2 gene knockout (TNFR2−/−) mice were used in this study. The results show that peripheral challenge by LPS, Iba1+- or CD11b+-microglia increase in numbers in the cortex and hippocampus of TNFR2−/− mice, when compared to WT or TNFR2+/− mice. We further conducted the intracerebral implantation of rodent glioma cells into the animals and found that the volumes of tumors formed by rat C6 glioma cells or mouse GL261 glioma cells were significantly larger in the cortex of TNFR2−/− mice when compared to that measured in LPS-primed WT or LPS-primed TNFR2+/− mice. Ki67+-cells were exclusively clustered in the tumor of LPS-primed TNFR2−/− mice. Microglia were also extensively accumulated in the tumor formed in LPS-primed TNFR2−/− mice. Accordingly, our findings demonstrate that aggravation of microglia activation by peripheral inflammatory challenge and a loss of TNFR2 function might lead to the promotion of glioma growth.

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SOLUBLE TUMOR NECROSIS FACTOR RECEPTOR TYPE 1 LEVELS EXHIBIT A STRONGER ASSOCIATION WITH RENAL OUTCOMES THAN TRADITIONAL RISK FACTORS IN CHINESE SUBJECTS WITH TYPE 2 DIABETES MELLITUS

Endocrine Practice ◽

10.4158/ep-2020-0114 ◽

2020 ◽

Vol 26 (10) ◽

pp. 1115-1124

Author(s):

Li-Hsin Chang ◽

Chii-Min Hwu ◽

Yi-Chun Lin ◽

Chin-Chou Huang ◽

Justin G.S. Won ◽

...

Keyword(s):

Type 2 Diabetes ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Diabetic Kidney Disease ◽

Tumor Necrosis Factor Receptor ◽

Receptor Type ◽

Renal Outcomes ◽

Necrosis Factor

Objective: Associations between albuminuria and renal outcomes are inconsistent in patients with type 2 diabetes (T2D). Soluble tumor necrosis factor receptor type 1 (sTNFR1) is involved in declined kidney function and poor renal outcomes but this has not been confirmed among Chinese T2D patients. This study aimed to examine the association of sTNFR1 and renal outcomes in a cohort of these patients. Methods: Two hundred and eighty-three Chinese T2D patients were enrolled in a prospective observational study which excluded individuals with estimated glomerular filtration rates (eGFR) <30 mL/min/1.73m2. Composite renal outcomes included either or both a >30% decline in eGFR and worsening albuminuria from consecutive tests of blood/urine during a 3.5-year follow-up. Results: Higher sTNFR1 levels were associated with impaired renal outcomes. sTNFR1 levels of ≥979 pg/mL yielded the most sensitivity and specific predictions of renal outcomes according to the receiver operating curve (area under the curve 0.68, P<.001; sensitivity 78.3%, specificity 48.9%). Renal events occurred more frequently in subjects with sTNFR1 ≥979 pg/mL than in others (sTNFR1 <979 pg/mL; 29% versus 10%; P<.001 by log-rank test). The association between sTNFR1 ≥979 pg/mL and renal outcomes remained significant after adjustment for relevant covariates (adjusted hazard ratio 2.43, 95% confidence interval 1.18 to 5.02; P = .01) and consistent across subgroups stratified by age, sex, blood pressure, eGFR, albuminuria, and the use of renin-angiotensin system inhibitors. Conclusion: Increased sTNFR1 levels were associated with renal outcomes in Chinese T2D subjects, making sTNFR1 a potential biomarker in diabetic kidney disease. Abbreviations: BMI = body mass index; CI = confidence interval; DKD = diabetic kidney disease; eGFR = estimated glomerular filtration rate; GLP-1a = glucagon-like peptide-1 agonist; HR = hazard ratio; RAS = reninangiotensin system; ROC = receiver operating characteristic; SGLT2i = inhibitors of the sodium glucose cotransporter; sTNFR1 = soluble tumor necrosis factor receptor type 1; T2D = type 2 diabetes; UACR = urinary albumin-creatinine ratio

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Ginsenoside metabolite compound K exerts joint-protective effect by interfering with synoviocyte function mediated by TNF-α and Tumor necrosis factor receptor type 2

European Journal of Pharmacology ◽

10.1016/j.ejphar.2015.12.019 ◽

2016 ◽

Vol 771 ◽

pp. 48-55 ◽

Cited By ~ 10

Author(s):

Ying Wang ◽

Jingyu Chen ◽

Xuexia Luo ◽

Ying Zhang ◽

Ming Si ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Protective Effect ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Receptor ◽

Receptor Type ◽

Compound K ◽

Tnf Α ◽

Necrosis Factor

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Deficient Expression of Tumor Necrosis Factor Receptor Type 2 in the Endometrium of Women with Endometriosis

American Journal Of Reproductive Immunology ◽

10.1034/j.1600-0897.2003.00058.x ◽

2003 ◽

Vol 50 (1) ◽

pp. 33-40 ◽

Cited By ~ 15

Author(s):

Abdelaziz Kharfi ◽

Yves Labelle ◽

Jacques Mailloux ◽

Ali Akoum

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Receptor ◽

Receptor Type ◽

Necrosis Factor

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Relationship between serum tumor necrosis factor receptor-2 concentration and periodontal destruction in patients with type 2 diabetes: Cross-sectional study

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1606266m ◽

2016 ◽

Vol 144 (5-6) ◽

pp. 266-272 ◽

Cited By ~ 1

Author(s):

Sanja Matic-Petrovic ◽

Ana Pucar ◽

Aleksandra Jotic ◽

Biljana Milicic ◽

Jelena Arambasic-Jovanovic ◽

...

Keyword(s):

Type 2 Diabetes ◽

Tumor Necrosis Factor ◽

Surface Area ◽

Tumor Necrosis ◽

Periodontal Diseases ◽

Tumor Necrosis Factor Receptor ◽

Enzyme Linked Immunosorbent Assay ◽

Periodontal Destruction ◽

Necrosis Factor

Introduction. The role of tumor necrosis factor-? (TNF?) is well documented in pathogenesis of chronic periodontitis (CP) and type 2 diabetes (T2D). Considering short half-life of TNF?, tumor necrosis factor receptor-2 (TNFR2) is used as prosperous surrogate marker of TNF? activity. Objective. The aim was to detect TNFR2 serum concentration and correlate it with periodontal destruction in patients with diagnosed T2D and nondiabetics. Methods. The study included 85 patients divided into three groups: T2D + CP (group T2D, n = 34); nondiabetics + CP (Group PD, n = 27); and healthy controls (group HC, n = 24). T2D was diagnosed according to WHO criteria (2013) and periodontitis was diagnosed using International Workshop for a Classification of Periodontal Diseases and Conditions criteria (1999). TNFR2 level was measured by enzyme-linked immunosorbent assay (ELISA). Results. There was no difference in TNFR2 level among the groups (Kruskal-Wallis, p = 0.482). Significant correlation (Pearson?s correlation coefficient) was observed between clinical attachment loss (CAL) and TNFR2 concentration in PD group (rp = -0.460, p = 0.016). In T2D group, correlations were observed between TNFR2 concentration and CAL (rp = 0.363, p = 0.005) and periodontal inflamed surface area (PISA) (rp = 0.345, p = 0.046) and periodontal epithelial surface area (PESA) (rp = 0.578, p = 0.000). Conclusion. Higher concentration of TNFR2 was associated with higher CAL, PESA, and PISA scores in T2D group. Contrary to that, nondiabetics with higher values of CAL exhibited lower concentration of TNFR2, presenting potential protective effect on periodontal destruction. These results imply that diabetes may alter TNFR2 secretion originated from periodontium.

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