Objective To investigate the effects of expression of TNFα mRNA on glucose uptake in both the liver and skeletal muscle after endotoxemia. Methods In the mice with intraperitoneal injection of lipopolysaccharide (LPS), the changes of TNFα level of plasma and uptake of 2-deoxyglucose (2-DG) in the isolated soleus muscle and hepatic tissues were determined, then the reinstatement of glucose uptake by injecting TNF-McAb for 3 days was also observed. In addition, changes of TNFα mRNA expression of liver were evaluated. Results The expression of TNFα mRNA in the liver showed markedly increased in the first 3 hours post endotoxemia and remaind high for 3 days, and the plasma TNFα level paralleled with TNFα mRNA expression of liver also was elevated. The basal uptake of 2-DG both in muscle and liver were markedly increased, but the stimulated 2-DG uptake with insulin was greatly reduced as compared with the control. In addition, these abnormalities of 2-DG uptake can be partially corrected by neutralization of the circulatory TNFα by administration of TNF-McAb. Conclusion The disorders of glucose uptake of the liver and the muscle due to the overexpression of TNFα mRNA and elevated circulatory TNFα level may be the mechanism of insulin resistance after endotoxemia.
【Abstract】 Objective To investigate the expression and significance of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors in pancreatic cancer. Methods Thirty-two samples of pancreatic cancer tissue were collected from year 2002 to 2004. All of them were verified by histopathology and there were 9 cases of well-differentiated, 12 of moderately differentiated, and 11 of poorly differentiated, in which 12 cases were in the stage of Ⅰor Ⅱand 20 in the stage of Ⅲ or Ⅳ according to the TNM staging method. Eighteen normal pancreatic tissues were used as control group. The expressions of TRAIL receptors (death receptor 4, death receptor 5, decoy receptor 4 and decoy receptor 5) mRNA were assayed by semi-quantitive reverse transcription polymerase chain reaction (RT-PCR) in the pancreatic cancer tissues and the normal pancreatic tissues. Results The expressions of death receptor 4 (DR4) and death receptor 5 (DR5) were detected in all the pancreatic cancer tissues and the normal pancreatic tissues and the levels of DR4 and DR5 were significantly higher than those of the normal pancreatic tissues (P＜0.01). Decoy receptor 1 (DcR1) and decoy receptor 2 (DcR2) were also expressed in normal pancreatic tissues, whereas DcR1 and DcR2 were only expressed in 18 and 20 pancreatic cancer tissues, respectively. However, there were no significant difference of the expression of DcR1 and DcR2 between the pancreatic cancer tissues and the normal pancreatic tissues （Pgt;0.05）. The expression level of DR5 in pancreatic cancer tissue was correlated with tumor differentiation and clinical stage, and the levels in stage Ⅲ and stage Ⅳwere significantly lower than those of stageⅠand stageⅡ(P＜0.05). The expressions of DR4, DcR1 and DcR2 were not correlated with tumor differentiation and clinical stage (Pgt;0.05). Conclusion ①The expression of TRAIL receptors in pancreatic cancer tissues is prevalent, but the types of receptors expressed in different tissues were also different. High expression of death receptors may play an important role in TRAIL recptors regulated pancreatic cancer apoptosis. ②The expression of DR5 is correlated with the differentiation degree of pancreatic cancer cell and clinical stage of tumor. The expressions of DR4, DcR1 and DcR2 should not be considered as related indexes of differentiation degree or clinical stage of pancreatic cancer.
ObjectiveTo investigate the effects of transforming growth factor-β (TGF-β) in choroidal neovascularization (CNV) induced by laser in mice. Methods Eighty male C57BL/6J mice at the age of 6-8 weeks old were randomly divided into the normal control, photocoagulation model, photocoagulation with phosphate buffered saline (PBS control group) and photocoagulation with TGF-β receptor inhibitor groups (TGF-β receptor inhibitor group), twenty mice of each group. Fundus argon laser photocoagulation was performed in the photocoagulation model group, PBS control group and TGF-β receptor inhibitor group to induce CNV. One week, two, three and four weeks after the laser procedure, fundus fluorescein angiography (FFA) was carried out in the normal control or photocoagulation model groups to observe CNV formation dynamically. Western blot was used to analyze the expressions of TGF-β in the retina from the mice of normal control or photocoagulation model groups, and VEGF or TNF-α in the retina of normal control, PBS control or TGF-β receptor inhibitor groups. The CNV areas of each group were evaluated by using fluorescein stain on retinal pigment epithelium (RPE)/choroid flat mounts after two weeks of photocoagulation. ResultsThe FFA results showed the retinal vessels centered on the optic disc and arranged radially, while the choroidal vascular present network distribution in the normal control mice. Significant leakage of fluorescein showed discoid strong fluorophore in photocoagulation sites of retina at one week after photocoagulation. The quantitative analysis results of Western blot demonstrated that the TGF-β protein expression levels in retina of photocoagulation model mice gradually increased with time passing. The protein expression levels of TGF-β were significant differences in the photocoagulation model group comparing with the normal control group (F=13.042, P < 0.05). The protein expression levels of TNF-α (F=14.721, 17.509) and VEGF (F=18.890, 11.251) increased significantly in retina of PBS control or TGF-β receptor inhibitor groups when compared with that of normal control group at one week, two, three and four weeks after photocoagulation, and the differences were both statistically significant (P < 0.05). Compared with PBS control group, the protein levels of TNF-α and VEGF in retina from TGF-β receptor inhibitor group were significantly reduced, the differences was statistically significant (F=21.321, 16.160, P < 0.05). Two weeks after laser photocoagulation, a distinct reduction in CNV lesion size in the TGF-β receptor inhibitor group mice when compared to PBS or normal control groups, the differences was statically significant (F=4.482, P < 0.05). ConclusionTGF-β may promote CNV formation by up-regulating both TNF-α and VEGF protein expressions, the application of its specific inhibitor is able to reduce CNV progression.
ObjectiveTo investigate the expression of tumor necrosis factor-α (TNF-α) in prostate cancer tissue and explore its relations with tumor angiogenesis. MethodsThe expression of TNF-α and CD105 were detected with two-step immunohistochemical staining technique in 20 cases of benign prostatic hyperplasia and 50 cases of prostate cancer between January 2010 and January 2012, and microvessel density (MVD) marked with CD105 was also measured. ResultsThe expressions of TNF-α and CD105 were higher in prostate cancer (41.72±8.67, 20.15±2.67) than those in benign prostatic hyperplasia (21.01±3.85, 4.34±1.67) (t'=13.990, P<0.001; t'=29.771, P<0.001). TNF-α and MVD were not correlated with age and size of tumor, but were positively correlated with tumor differentiation degree (rs=0.847, P<0.001; rs=0.776, P<0.001) and negatively correlated with clinical grades (rs=-0.769, P<0.001; rs=-0.842, P<0.001). ConclusionThe result indicates that over expression of TNF-α exists in prostate cancer. It may play an important role in the anginogenesis and carcinogenesis of prostate cancer.
ObjectiveTo explore the correlation between the degree of bone marrow edema (BME) and the content change of tumor necrosis factor α (TNF-α) and matrix metalloproteinase 3 (MMP-3) and the knee pain symptoms in patients with bone contusion around the knee joint. MethodsThirty patients (30 knees) of bone contusion around the knee joint were chosen as the trial group between October 2009 and April 2012. According to visual analogue scale (VAS), 30 patients were divided into mild group (10 cases), moderate group (10 cases), and severe group (10 cases); according to MRI morphological changes, the patients were divided into type I group (12 cases), type Ⅱ group (11 cases), and type Ⅲ group (7 cases). Ten patients (10 knees) with soft tissue injury of the knee were chosen as control group. No significant difference was found (P>0.05) in gender, age, causes, side, and admission time after injury between 2 groups. The serum contents of MMP-3 and TNF-α were detected and statistically analysed between different degrees of pain groups and between different degrees of BME groups. Correlation was analysed between BME and inflammatory factor changes and VAS score. ResultsThe MMP-3 and TNF-α contents in trial group[(29.580±6.870) μg/L and (23.750±7.096) ng/L] were significantly higher than those in control group[(8.219±1.355) μg/L and (6.485±1.168) ng/L](t=9.686, P=0.000; t=7.596, P=0.000). The MMP-3 and TNF-α contents in patients with different degrees of pain and BME were significantly higher than those in patients of control group (P<0.05), and significant difference was found between patients with different degrees of pain (P<0.05), but no significant difference between patients with different degrees of BME (P>0.05). Multiple linear regression analysis showed that TNF-α content was significantly correlated with VAS score (P=0.000). ConclusionKnee pain symptoms are not related to the degree of BME in patients with bone contusion around the knee joint. Inflammatory factor TNF-α content is the main influence factor of knee joint pain symptoms.
Objective To investigate the mechanism of the resistance of pancreatic cancer cells to tumor necrosis factor related apoptosis inducing ligand (TRAIL)mediated apoptosis. MethodsThe expression of TRAIL receptor-4 (TRAIL-R4) in normal pancreas tissue and pancreatic cancer was analyzed by using Northern blotting, Western blotting and immunohistochemistry.ResultsTRAIL-R4 mRNA and protein were expressed at moderate to high levels in human pancreatic cancer, but demonstrated weak to negative in the normal pancreas. Moreover, pancreatic cancer cells showed b TRAIL-R4 immunostaining throughout the tumor mass. Conclusion TRAIL-R4 levels are significantly different in pancreatic cancer in comparison to the normal pancreas. These findings give new insights into the resistance mechanisms of pancreatic cancer cells towards TRAILmediated apoptosis.
Objective To investigate the clinical significance of insulin resistance ( IR) in chronic obstructive pulmonary disease ( COPD) .Methods Patients with stable COPD were recruited while healthy volunteers were enrolled as control. The diagnosis and severity assessment were made according to chronic obstructive pulmonary disease diagnosis and treatment guideline ( revised edition 2007) . Fasting serum levels of glucose ( FBG) , insulin ( FIN) , blood lipids, fibrinogen, C-reactive protein ( CRP) , tumor necrosis factor ( TNF-α) , and interleukin-6 ( IL-6) were measured. The degree of IR was calculated by IAI( IAI =1/FBG ×FIN) . The relationship of IR with COPD severity and above parameters was analyzed. Results A total of 121 subjects with COPD were enrolled in which 22 cases of mild COPD, 28 cases of moderate COPD,34 cases of severe COPD, and 37 cases of extremely severe COPD. The levels of FBG and FIN were significantly higher in the COPD group than those in the normal control group ( P lt;0. 05) . ISI in the COPD patients was higher than that in the controls ( - 3. 88 ±0. 54 vs. - 3. 40 ±0. 28, P lt;0. 05) . The levels of CRP, fibrinogen, TNF-α, and IL-6 were significantly higher in the COPD group than those in the control group ( P lt;0. 05) . The levels of CRP, TNF-αand IL-6 increased progressively with the severity of COPD. There was a negative correlation between ISI and the severity of COPD ( r = - 0. 512, P lt; 0. 01) , positive correlations of CRP, fibrinogen, TNF-αand IL-6 levels with COPD severity, respectively( r=0. 710, 0. 600,0. 708,0. 707, all P lt;0. 01) , and negative correlations of ISI with the levels of CRP, fibrinogen, TNF-α and IL-6 ( r = - 0. 384, - 0. 240, - 0. 298, - 0. 396, all P lt; 0. 01) , respectively. Conclusion There is an increase in fasting serum insulin and insulin resistance in patients with COPD compared with healthy subjects, which deteriorates with severity of COPD.
Purpose To investigate the expression of the interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-alpha;) in epiretinal membranes(ERM) of eyes with proliferative vitreoretinopathy(PVR). Methods Nineteen epiretinal membranes were obtained form eyes undergoing vitrectomy for retinal detachment complicated with PVR and observed by immunohistochemical methods. Results Expression of IL-6 and TNF-alpha; were observed in 12 and 15 membranes respectively with positive staining mostly in extracellular matrix of epiretinal membranes.Only one membrane showed positive to IL-6 intracellularly,and expression for IL-6 and TNF-alpha; simultaneously in membranes. Conclusion The findings indicate that IL-6、and TNF-alpha;might be involved in the development of PVR. (Chin J Ocul Fundus Dis,1998,14:219-221)
PURPOSE:To measure the concentration changes of tumor necrosis factor a (TNF-alpha;)in vitreous during the development of experimental PVR induced by macrophages and explore the initial and mediated factors which stimulate the cellular proliferation. METHODS:Rabbit PVR model was induced by macrophages and the vitreous was taken at the 7th,14th,21st and 28th day and 4 eyes in each group. The TNF-alpha; levels in vivreous of the above examinated and control eyes were measured with an ELISA kit. RESULTS:The TNF-alpha; level in the vitreous reached its peak 434mu;g/ml at 21st day in the mod-el, then rappidly decreased to 122mu;g/ml at 28th day. CONCLUSION:The changes of TNF-a in the vitreous of the PVR model were parallel to the natrual phases of the development of PVR,indicating TNF-alpha; may play an important role in initiating and mediating the inflammation and cellular proliferation in the vitreous. （Chin J Ocul Fundus Dis,1997,13: 231-233）
Objective To summarize the role of inflammatory cytokines in the pathogenesis of acute pancreatitis (AP) and gut barrier dysfunction in recent years. Methods Literatures on cytokines and experimental pancreatitis as well as clinical pancreatitis were collected and reviewed. Results Tumor necrosis factor-α and other inflammatory cytokines were elevated significantly during pancreatitis in many tissues, especially in pancreas and alimentary tract, in a fashion independent of the animal model used. Anti-cytokine therapy could decrease the concentration of the cytokines in experimental animal. Conclusion Inflammatory cytokines are believed to be primarily responsible for the pathogenesis of acute pancreatitis and its associated distant organ dysfunction. Further study of the nature of these cytokines may provide a new approach to treating this disease.