Interferon-γ Receptor-Mediated but Not Tumor Necrosis Factor Receptor Type 1- or Type 2-Mediated Signaling Is Crucial for the Activation of Cerebral Blood Vessel Endothelial Cells and Microglia in Murine Toxoplasma Encephalitis

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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Aggregation of the intracellular domain of the type 1 tumor necrosis factor receptor defined by the two-hybrid system.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)31673-3 ◽

1994 ◽

Vol 269 (36) ◽

pp. 22492-22495 ◽

Cited By ~ 2

Author(s):

H.Y. Song ◽

J.D. Dunbar ◽

D.B. Donner

Keyword(s):

Tumor Necrosis Factor ◽

Hybrid System ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Receptor ◽

Intracellular Domain ◽

Two Hybrid ◽

Necrosis Factor

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Nitric Oxide Synthase mRNA in Endothelial Cells: Synergistic Induction by Interferon-γ, Tumor Necrosis Factor-α and Lipopolysaccharide and Inhibition by Dexamethasone

The Japanese Journal of Pharmacology ◽

10.1254/jjp.63.327 ◽

1993 ◽

Vol 63 (3) ◽

pp. 327-334 ◽

Cited By ~ 12

Author(s):

Takeshi MaruMo ◽

Toshio Nakaki ◽

Hiroko Adachi ◽

Hiroyasu Esumi ◽

Hiromichi Suzuki ◽

...

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Interferon Γ ◽

Synergistic Induction ◽

Factor Α ◽

Oxide Synthase ◽

Necrosis Factor

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Function and Regulation of Tumor Necrosis Factor Receptor Type 2

Current Medicinal Chemistry ◽

10.2174/0929867043364694 ◽

2004 ◽

Vol 11 (16) ◽

pp. 2205-2212 ◽

Cited By ~ 68

Author(s):

I. Carpentier ◽

B. Coornaert ◽

R. Beyaert

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Receptor ◽

Receptor Type ◽

Necrosis Factor

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Effect of interferon-γ and tumor necrosis factor on the expression of class I and class II major histocompatibility molecules by cultured human umbilical vein endothelial cells

Cellular Immunology ◽

10.1016/0008-8749(88)90046-9 ◽

1988 ◽

Vol 111 (1) ◽

pp. 1-9 ◽

Cited By ~ 47

Author(s):

Josiah F. Wedgwood ◽

Lynda Hatam ◽

Vincent R. Bonagura

Keyword(s):

Endothelial Cells ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Umbilical Vein ◽

Class Ii ◽

Interferon Γ ◽

Class I ◽

Human Umbilical Vein ◽

Umbilical Vein Endothelial Cells ◽

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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