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Molecular mechanism of signaling by tumor necrosis factor

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Science China Life Sciences 2002年第2期45卷 113-119页

作者：查纪坤舒红兵 1. College of Life Sciences Peking University 100871 Beijing China 2. National Jewish Medical and Research Center 80206 Denver CO USA

tumor necrosis factor (TNF) is an important cytokine with multiple biological effects, including cell growth, differentiation, apoptosis, immune regulation and induction of inflammation. The effects of TNF are mediated by two receptors, TNF-R1 and TNF-R2. The major signal trans-duction pathways triggered by TNF include those that lead to apoptosis, activation of transcription factor NF-κB and protein kinase JNK. This review will discuss the molecular mechanisms of these signaling pathways.

关键词： tumor necrosis factor signal transduction JNK kinase NF-κB apoptosis.

tumor necrosis factor-alpha blockage therapy impairs hepatitis B viral clearance and enhances T-cell exhaustion in a mouse model

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Cellular & Molecular Immunology 2015年第3期12卷 317-325页

作者： Hsu Chyuan Hwei-Fang Tsai Horng-Tay Tzeng Chi-Chang Sung Chien-Sheng Wu Pei-Jer Chen Ping-Ning Hsu Department of Internal Medicine Cathay General Hospital Taipei Taiwan China Department of Internal Medicine Taipei Medical University 5iquang HOHospital Taipei Taiwan China Institute of Clinical Medicine College of Medicine Taipei Medical University Taipei Taiwan China Graduate Institute ofImmunology College of Medicine National Taiwan University Taipei Taiwan China Department of Internal Medicine Far Eastern Memorial Hospital NewTaipei City Taiwan China Graduate Institute of Clinical Medicine College of Medicine National Taiwan University Taipei Taiwan China Departmentof Internal Medicine National Taiwan University Hospital Taipei Taiwan China These authors contributed equally to this work.

Hepatitis B virus （HBV） reactivation and recurrence are common in patients undergoing immunosuppression therapy. tumor necrosis factor （TNF） blockage therapy is effective for the treatment of many autoimmune inflammatory diseases. However, the role of TNF-a blockage therapy in the innate and adaptive immune responses against HBV is still not clear. A detailed analysis of HBV infection under TNF-a blockage therapy is essential for the prophylaxis and therapy for HBV reactivation and recurrence. In this study, HBV clearance and T-cell responses were analyzed in a HBV-transfected mouse model under anti-TNF blockage therapy. Our results demonstrated that under TNF-a blockage therapy, HBV viral clearance was impaired with persistent elevated HBV viral load in a dose- and temporal-dependent manner. The impairment of HBV clearance under anti-TNF-a blockage therapy occurred at early time points after HBV infection. In addition, TNF-a blockade maintained a higher serum HBV viral load and increased the number of intrahepatic programmed cell death （PD）- 1highCD127low exhausted T cells. Furthermore, TNF-a blockade abolished Toll-like receptor 9 （TLR9） ligand-induced facilitation of HBV viral clearance. Taken together, TNF-a blockade impairs HBV clearance and enhances viral load, and these effects depend on early administration after HBV infection. Our results here demonstrate that early TNF-a blockade reduces viral clearance and persistently maintains elevated HBV viral load in a mouse model, suggesting that HBV may reactivate during theraoy with TNF-a-blocking agents.

关键词： HBV viral load hepatitis B virus tumor necrosis factor

Detection of tumor necrosis factor Gene by Piezoelectric Nucleic Acid Sensor

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Chinese Journal of Chemistry 2002年第10期20卷 1044-1048页

作者：胡毅周晓东刘栗佳胡敏裴仁军胡继明 CollegeofLifeSciences WuhanUniversityWuhanHubei430072China DepartmentofAnalysis－MeasurementScience WuhanUniversityWuhanHubei430072China

A piezoelectric nucleic acid sensor was constructed for detection of tumor necrosis factor gene. Two methods were employed for immobilization of nucleic acid probe on gold electrode of piezoelectric crystal. The results show that polyethyleneimine adhesion and glutaraldehyde cross-linking method has higher sensitivity, stability and selectivity than protein A method. The solid-phase nucleic acid hybridization of oligo nucleotides and tumor necrosis factor target gene sequence were monitored using this sensor. tumor necrosis factor gene sequence (580 bp) was detected by this nucleic acid sensor for the first time.

关键词： nucleic acid sensor quartz crystal microbalance tumor necrosis factor

tumor necrosis factor gene polymorphisms and endometriosis in Asians： a systematic review and meta-analysis

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Chinese Medical Journal 2014年第9期127卷 1761-1767页

作者： Lyu Jiangtao Yang Hua Lang Jinghe Tan Xianjie Department of Obstetrics & Gynecology Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730 China

Background Numerous studies have described the association between polymorphisms in the tumor necrosis factor （TNF） gene and risk of ***,the results remain *** we reviewed studies reporting the association between TNF gene polymorphisms and endometriosis risk in *** PubMed and Embase were *** case-control studies assessing the role of multiple TNF gene polymorphisms in endometriosis were *** no less than two articles evaluated one variant,meta-analysis was conducted; otherwise,narrative analysis was chosen.A fixed-or random-effects model was employed according to the heterogeneity among *** strength of the association between TNF gene polymorphisms and endometriosis risk was assessed by odds ratios and 95％ confidence *** For TNF-α-238G＞A,-308G＞A,-857C＞T,and-863C＞A,no significant associations were identified from all genetic *** TNF-α-850T＞C,results from one study showed that patients harboring the heterozygote TC were less susceptible to endometriosis than patients harboring the homozygote *** TNF-α-1031T＞C,a mild increase in endometriosis risk was found in the Asian ***-analysis from two studies found that the TNF-β ＋252＞G polymorphism had a protective effect in Chinese *** to the limitations of the included studies,it is necessitated to perform more studies to elucidate the possible roles of TNF gene polymorphisms in the pathogenesis of *** TNF-α-1031T＞C and TNF-β ＋252A＞G were significantly associated with the risk of endometriosis in Asian and Chinese populations,*** further evaluate these associations,more large-scale,rigorously designed studies are needed.

关键词： tumor necrosis factor genetic polymorphism endometriosis meta-analysis

THE ASSOCIATION BETWEEN tumor necrosis factorαGENE POLYMORPHISM AND ASTHMA

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Chinese Medical Sciences Journal 2003年第4期18卷 248-253页

作者：高金明林耀广邱长春刘怡雯马毅刘英 Department of Respiratory Disease PUMC HospitalCAMS &PUMCBeijing100730 National Laboratory of Medical Molecular Biology Institute of Basic Medical ScienceCAMS & PUMCBeijing 100005

*** this study,we investigated the hypothesis that tumor necrosis factor(TNF)α-308gene polymorphism might be of the genetic predisposition to asthma and asthma ***α-308gene polymorphism was genotyped in221random unrelated Northern Chinese population(comprising125asthmatics and96healthy controls)and52individuals from12asthmatic families with Han ethnic by using polymerase chain reaction(PCR)-restriction fragment length polymor-phism(RFLP).Methacholine(Mch)broncho-challenge test,bronchial reversibility test and lung function were underwent in all ***α-3082homozygosity was present at a significantly higher frequency in asthmatics than that in controls(20.8%vs11.4%,Pfactor for asthma etiology(OR0.226,P<0.05).Moreover,patients carrying TNFα-3082homozy-gosity had less responsive to inhaledβ 2 -agonist in20minutes than patients carrying other two genotypes(24.1%vs29.5%vs38.8%,P<0.05).Linkage analysis didn’t support that TNFαgene was linked to asthma (Likelihood of odds,LOD<1)based on familial *** These results suggest that TNFα-3082homozygosity may be of a component contribut-ing to the genetic predisposition to asthma ,and airway responsiveness toβ2 -agonist.

关键词： tumor necrosis factor asthma genetic

ROLE OF tumor necrosis factor IN NEONATAL SEPSIS

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Chinese Medical Sciences Journal 1994年第1期9卷 45-48页

作者：史源沈际臬汪江淮李华强覃世文刘韧 Department of Pediatrics Daping Hospital Third Military Medical University Chongqing.

In order to assess the role of tumor necrosis factor (TNF) in neonatal sepsis, plasma TNF levels were determined by a method using L929 cells at the time of septic work-up in 67 neonates. Thirty-three patients, with sepsis were found to have significantly higher TNF levels (533. 33 ±468. 74 U/ml ; 1 U corresponding to 1. 67 pg recombinant TNF) as compared with 34 non-sepsis patients (100. 0±188, 97 U/ml) and 30 healthy newborns (27. 33±1 6. 1 7 U/ml, P<0. 05. respectively) . The upper limit of normal plasma TNF levels was 60 U/ml and the best cutoff value for predicting neonatal sepsis was 160 U/ml. This had remarkable sensitivity (88%), specificity (82%). positive predictive value (83%). and negative predictive value (88%). Plasma TNF levels were significantly associated with the occurrence of shock,organ failure. sclerema and outcome. Thus, anti-TNF antibodies might be used in protecting newborns from septic death.

关键词： tumor necrosis factor sepsis infant newborn

Effects of tumor necrosis factor-alpha on calcium movement in rat ventricular myocytes

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Acta Pharmacologica Sinica 2003年第12期 50-56页

作者： LI Xiao-Qiang, ZHAO Ming-Gao, MEI Qi-Bing~2, ZHANG Yan-Feng CAO Wei, WANG Hai-Fang, CHEN Dan~3, CUI Yi Department of Pharmacology, ~3Electron Microscopy Center, The Fourth Military Medical University, Xi-an 710032, China

AIM: To study the effects of tumor necrosis factor-alpha (TNF-α) on calcium movement in rat ventricular myocytes. METHODS: Intracellular free Ca2+concentration was measured with calcium fluorescent probe Fluo-3/AM and laser confocal microscope. L-type calcium current (ICa.L) was recorded with the whole-cell configuration of the patch-clamp techniques. RESULTS: At 2, 20 and 200μg/L, TNF-α was found to increase intracellular free Ca2+concentration in a dose-dependent manner illustrated by the increment of calcium fluorescence density with laser confocal microscope. Nicardipine 0.5μtmol/L slightly attenuated TNF-α-induced response. When the cardiac myocytes were exposed to caffeine (100mmol/L) for 30 rain, TNF-α failed to induce any change of intracellular free calcium. However, it was found that TNF-α inhibited *** whole-cell patch-clamp experiments. At 2, 20, and 200μg/L, TNF-α decreased peak *** 3.9％ (-5.1 pA/pF±0.3 pA/pF vs -4.9 pA/pF±0.2 pA/pF, n=9, P>0.05), 15.7

关键词： tumor necrosis factor myocardium calcium: patch-clamp techniques confocal microscopy

tumor necrosis factor-α and interleukin-6 in cirrhotic patients with spontaneous bacterial peritonitis

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World Journal of Gastrointestinal Pathophysiology 2012年第5期3卷 92-98页

作者： Muhammed AM Suliman Fawzy MH Khalil Salam SA Alkindi Anil V Pathare Ali AA Almadhani Neveen AAI Soliman Department of Medicine Sohar HospitalSohar 311Oman Department of Medicine Benha UniversityBenha 13511Egypt Department of Haematology Sultan Qaboos UniversityMuscat 123Oman

AIM: To evaluate the role of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cirrhotic patients who have hepatic and renal impairment with spontaneous bacterial peritonitis (SBP).

关键词： tumor necrosis factor Interleukin-6 Spontaneous bacterial peritonitis Cirrhosis tumor necrosis factor

Dynamic changes of interleukin-1, interleukin-6 and tumor necrosis factor in intermingled skin graft in burned rats

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Chinese Journal of Traumatology 2001年第1期4卷 31-36页

作者：吴建和赵雁飞胡宝瑜童善庆朱德安陆德源史济湘 DepartmentofMicrobiology ShanghaiSecondMedicalUniversity DepartmentofPathology ShanghaiSecondMedicalUniversity InstituteofBurnResearch RuijinHospitalShanghaiSecondMedicalUniversity

To compare the dynamic changes of interleukin 1 (IL 1), interleukin 6 (IL 6), and tumor necrosis factor (TNF) in intermingled skin graft with those in other types of skin grafts in rats. Methods: A 10% 15% third degree burn was created in 180 Spregue Dawley (SD) rats. After removing the scar, skin grafts were performed on the open wounds immediately with autoskin (aus, n=54), alloskin (als, n=54) and intermingled skin (n=36). That is to say, in the intermingled skin graft, a big piece of alloskin (mals) was grafted first, and 3 days later, small pieces of autoskin (maus) were embedded in the alloskin. The rest 36 rats were taken as the controls. And the biological activities of IL 1, IL 6 and TNF in graft sheets in each group were detected after skin graft. Results: The levels of IL 1, IL 6 and TNF in the aus group decreased steadily after their initial elevations, whereas in the als group they increased significantly and kept on the peak level in the later phases. In the intermingled group, there appeared a lowest IL 1 level in the mals and a highest one in the maus simultaneously at 7 (4) days (The number out of parenthesis is the days after transplanting with alloskin sheets, and the number in parenthesis is the days after embedding autoskin sheets in the intermingled skin graft. Similarly hereinafter.) after skin graft (Pfactors to lighten the intensity of local rejection in the intermingled skin graft. The temporaril

关键词： Skin transplantation Burns Interleukin 1 Interleukin 6 tumor necrosis factor