目的研究骨转换标志物及其与总前列腺特异抗原(total prostate specific antigen,tPSA)、白细胞介素⁃6(interleukin⁃6,IL⁃6)构建的预测模型在前列腺癌骨转移中的临床应用价值。方法比较分析骨钙素(N⁃MID osteocalcin,Osteocalcin)、总I...目的研究骨转换标志物及其与总前列腺特异抗原(total prostate specific antigen,tPSA)、白细胞介素⁃6(interleukin⁃6,IL⁃6)构建的预测模型在前列腺癌骨转移中的临床应用价值。方法比较分析骨钙素(N⁃MID osteocalcin,Osteocalcin)、总I型前胶原氨基末端肽(total procollagen type 1 amino⁃terminal pro⁃peptide,TPINP)、β⁃异构化的C⁃端肽I型胶原片段(β⁃CrossLaps,β⁃CTx)、tPSA、IL⁃6在发生和未发生骨转移的前列腺癌患者血清中的表达差异;运用logistic回归分析,从上述血清标志物中筛选出前列腺癌骨转移的危险因素。并通过筛选的危险因素,构建前列腺癌骨转移的预测模型,进一步绘制ROC曲线评估该预测模型在前列腺癌骨转移中的诊断效能。结果Osteocalcin、TPINP、β⁃CTx及tPSA、IL⁃6在前列腺癌骨转移患者中的表达水平均显著高于未发生骨转移患者(P<0.05);其中Osteocalcin、TPINP、tPSA、IL⁃6为前列腺癌骨转移的独立危险因素(OR=1.088、1.021、1.037、1.415,P<0.05);通过上述危险因素构建的预测模型为logit(P)=(-5.058)+0.085×(Osteocalcin)+0.020×(TPINP)+0.037×(tPSA)+0.347×(IL⁃6),该模型在前列腺癌骨转移诊断中的曲线下面积(AUC)=0.908(P<0.001)。结论前列腺癌骨转移患者存在异常的骨代谢;且由Osteocalcin、TPINP、tPSA、IL⁃6构建的数学模型能够较好地预测前列腺癌骨转移的发生。展开更多
Recombinant E.coli JM109, containing pHZ1818 plasmid which included the fused gene encoding human interleukin 6(IL 6), expressed a fusion protein with glutathion S transferase(GST). The fusion protein existed both...Recombinant E.coli JM109, containing pHZ1818 plasmid which included the fused gene encoding human interleukin 6(IL 6), expressed a fusion protein with glutathion S transferase(GST). The fusion protein existed both in the supernatant and inside the bacterial cell,but the insoluble protein had no biological activity and could not be refolded. The rotative speed of the shaker and the temperature of induction were optimized to maximize the expression of the soluble fusion protein. From the supernatant of the cell sonicates Glutathion Sephrose 4B affinity column chromatography was employed to isolate the fusion protein which could be purified to >80 0 0 in a single step. The yield of soluble GST IL 6 was about 10 mg per liter culture. The GST was site specifically cloven by 6 hours of treatment with thrombin and from the thrombin digest mixture IL 6 was purified by Q high performance ion exchange chromatography. From 1 liter of E.coli culture 2 mg refined IL 6 was obtained. The purified IL 6 had a purity of more than 95 0 0 and a biological activity of 1.02×10 8 IU/mg.展开更多
The tumor microenvironment （TME） plays a prominent role in the growth of tumor cells. As the major inflammatory component of the TME, M2d macrophages are educated by the TME such that they adopt an immunosnppressive...The tumor microenvironment （TME） plays a prominent role in the growth of tumor cells. As the major inflammatory component of the TME, M2d macrophages are educated by the TME such that they adopt an immunosnppressive role that promotes tumor metastasis and progression. Fra-1 forms activator protein-1 heterodimers with Jun partners and drives gene transcription. Fra-1 is thought to drastically induce tumorigenesis and progression. However, the functional role of Fra-1 in the generation of M2d macrophages is poorly understood to date. Here, we demonstrate that 4T1 mammary carcinoma cells, when co-cultured with RAW264.7 macrophage cells, skew the RAW264.7 macrophage cell differentiation into M2d macrophages. The 4T1 cells stimulate de novo overexpression of Fra-1 in RAW264.7 cells, and then Fra-1 binds to the interleukin 6 （IL-6） promoter to increase the production of the cytokine IL-6 in RAW264.7 cells. IL-6 acts in an autocrine fashion to skew RAW264.7 macrophage cell differentiation into M2d macrophages. These findings open new insights into how to reverse M2d macrophage-induced immune tolerance to improve the efficacy of immunotherapeutic approaches.展开更多
AIM:The current study was to determine the serum/pLasma levels of VEGF,IL-6,malondialdehyde (MDA),nitric oxide (NO),PCT and CRP in gastric carcinoma and correlation with the stages of the disease and accompanying infe...AIM:The current study was to determine the serum/pLasma levels of VEGF,IL-6,malondialdehyde (MDA),nitric oxide (NO),PCT and CRP in gastric carcinoma and correlation with the stages of the disease and accompanying infection. METHODS:We examined the levels of serum VEGF,IL-6, PCT,CRP and plasma MDA,NO in 42 preoperative gastric cancer patients and 23 healthy subjects.There were infection anamneses that had no definite origin in 19 cancer patients. RESULTS:The VEGF levels (mean±SD; pg/mL) were 478.05±178.29 and 473.85±131.24 in gastric cancer patients with and without infection,respectively,and these values were not significantly different (P>0.05).The levels of VEGF, CRP,PCT,It-6,MDA and NO in cancer patients were significantly higher than those in healthy controls and the levels of CRP,PCT,It-6,MDA and NO were statistically increased in infection group when compared with non- infection group (P<0.001). CONCLUSION:Although serum VEGF concentrations were increased in gastric cancer,this increase might not be related to infection.CRP,PCT,IL-6,MDA and NO have obvious drawbacks in the diagnosis of infections in cancer patients. These markers may not help to identify infections in the primary evaluation of cancer patients and hence to avoid unnecessary antibiotic treatments as well as hospitalization. According to the results of this study,IL-6,MDA,NO and especially VEGF can be used as useful parameters to diagnose and grade gastric cancer.展开更多
AIM： To evaluate the immunohistochemical localization of interleukin-6 （IL-6） and IL-6 receptor （IL-6R） on tumor tissue specimens from patients with hepatocellular carcinoma （HCC） and the serum levels of IL-6 a...AIM： To evaluate the immunohistochemical localization of interleukin-6 （IL-6） and IL-6 receptor （IL-6R） on tumor tissue specimens from patients with hepatocellular carcinoma （HCC） and the serum levels of IL-6 and sIL-6R in a group of patients with HCC as well as liver cirrhosis （LC） in a group of patients with LC alone and in a control group. METHODS： Three groups of subjects were studied： group Ⅰ （n =83） suffering from HCC and LC, group Ⅱ （n = 72） suffering from LC alone and group Ⅲ （n =42） as healthy controls. All patients had hepatitis C virus infection. Serum IL-6 and IL-6R levels were determined using a commercially available ELISA kit. Immunohistochemistry was performed using the streptavidin-biotin complex and rabbit polyclonal antibodies against IL-6 and IL-6R. RESULTS： Immunohistochemistry analysis showed a medium to strong cytoplasmic and membrane reactivity for IL-6 and IL-6R respectively, in at least 40% of cases of HCC, whereas liver cirrhosis patients and controls were negative for IL-6 or showed a very mild and focal dot-like cytoplasmic reaction for IL-6R. Serum IL-6 levels in HCC group were significantly higher than those in LC and control groups （P〈 0.0001）. There was no significant difference in sIL-6R concentrations among 3 groups. When the patients with HCC were divided into groups according to Okuda＇s classification, a significant serum increase of IL-6 and slL-6R level was observed from stage Ⅰ to stage Ⅲ （P〈0.02, P〈0.0005）. When HCC and LC patients were divided into 3 classes of cirrhosis severity according to Child-Pugh, values in HCC patients were significantly higher than those in LC patients for each corresponding class （P〈 0.01）. CONCLUSION： IL-6 serum levels in HCC patients are higher than those in LC patients and controls, suggesting an increased production of this cytokine by neoplastic cells, sIL-6R values are similar in all groups, increasing only in stage III HCC patients. These data suggest that they have a closer relationship with the neoplastic mass rather than with the residual functioning hepatic mass.展开更多
AIM： To investigate the correlation between the expression levels of interleukin （IL）-6 and proteins in tight junctions （TJs） in the esophageal mucosa of rats modeling different types of reflux esophagitis （RE）...AIM： To investigate the correlation between the expression levels of interleukin （IL）-6 and proteins in tight junctions （TJs） in the esophageal mucosa of rats modeling different types of reflux esophagitis （RE）, and the ability of aluminum phosphate to protect against RE-induced mucosal damage via these proteins. METHODS： Male SPF Wistar rats aged 56 d were divided randomly into acid RE, alkaline RE, mixed RE, and control groups. Various surgical procedures were performed to establish rat models of acid RE. At 14 d after the procedure, some of the rats started aluminum phosphate treatment. Transmission electron microscopy （TEM） was used to observe the morphological features of TJs and desmosomes in the esophageal epithelium. Immunohistochemical methods and Western blotting were used to measure expression of claudin 1, occludin, ZO-1, JAM-l, DSG-1 and IL-6; reverse transcription polymerase chain reaction （RT- PCR） was used to measure expression of mRNA of claudin 1, occludin, ZO-1, JAM-1, DSG-1 and IL-6. RESULTS： At day 14 alter the procedures, an RE model was established in all subsequently sacrificed rats of groups A, B and C. By both gross and microscopic observation, the mucosa was damaged and thickened as the disease progressed. With TEM observation, a widened intercellular space was noticed, with significantly fewer desmosomes. Immunohistochemistry showed significantly higher levels of all proteins in all RE models compared to control rats at 3 d after operation （65.5% ± 25.6% vs 20.5% ± 2.1%, P 〈 0.05, respectively）. At 14 d after operation, along with continuing hyperplasia in the basal layer, the expression of TJ proteins in individual cells gradually decreased （12.4% ± 2.1% vs 20.5% ± 2.1%, P 〈 0.05, respectively）. Western blottings and RT-PCR showed a directly proportional increase in IL-6 levels in relation to TJ proteins, as compared to controls （0.878 ± 0.024 vs 0.205 ± 0.021 and 0.898±0.022 vs 0.205 ± 0.021, P 〈 0.05, respectively）. Upon treatment with aluminum phosphate, however, these protein levels were restored to normal gradually over 30-60 d in rats with acid RE （30.4% ± 2.1% vs 20.5% ± 2.1%, P 〉 0.05, treated vs untreated, respectively）. These levels increased in the rat with alkaline RE, and this increase was accompanied by continued hyperplasia in comparison with controls （85.5% ± 25.6% vs 20.5% ± 2.1%, P 〈 0.05, respectively）. Furthermore, the expression of TJ proteins was not correlated significantly with that of IL-6 in this group. CONCLUSION： These findings indicate that TJ proteins are highly expressed as an early molecular event involved in RE development, and that IL-6 is an inflammatory factor in this process,展开更多
AIM： To evaluate whether the effect of Gin dipeptideenriched total parenteral nutrition （TPN） on postoperative cytokine alteration depended on the disease severity of surgical patients. METHODS： Forty-eight patien...AIM： To evaluate whether the effect of Gin dipeptideenriched total parenteral nutrition （TPN） on postoperative cytokine alteration depended on the disease severity of surgical patients. METHODS： Forty-eight patients with major abdominal surgery were allocated to two groups to receive isonitrogenous （0.228 g nitrogen/kg per d） and isocaloric （30 kcal/kg per d） TPN for 6 d. Control group （Cony） using conventional TPN solution received 1.5 g amino acids/kg per day, whereas the test group received 0.972 g amino acids/kg per day and 0.417 g L-alanyI-L-glutamine （Ala-GIn）/kg per day. Blood samples were collected on d 1 and d 6 postoperatively for plasma interleukin （IL）-2, IL-6, IL-8, and interferon （IFN）-γ analysis. RESULTS： Plasma IL-2 and IFN-γ were not detectable. IL-6 concentrations were significantly lower on the 6^th postoperative day in the Ala-GIn group than those in the Cony group in patients with APACHE Ⅱ≤6, whereas no difference was noted in patients with APACHE Ⅱ〉6. There was no difference in IL-8 levels between the two groups. No difference in cumulative nitrogen balance was observed on d 2-5 after the operation between the two groups （Ala-GIn -3.2±1.6 g vs Cony -6.5±2.7 g）. A significant inverse correlation was noted between plasma IL-6 levels and cumulative nitrogen balance postoperatively in the Ala-GIn group, whereas no such correlation was observed in the Conv group. CONCLUSION： TPN supplemented with Gin dipeptide had no effect on plasma IL-8 levels after surgery. However, Gin supplementation had a beneficial effect on decreasing systemic IL-6 production after surgery in patients with low admission illness severity, and lower plasma IL-6 may improve nitrogen balance in patients with abdominal surgery when Gin was administered.展开更多
Objective To investigate the effect of interleukin-6 （ IL-6 ） on the apoptosis of annulus fibrosus （AF） cell induced by intedeukin-1β （IL-1β）. Methods Cultured AF cells were divided into 6 groups and treated ...Objective To investigate the effect of interleukin-6 （ IL-6 ） on the apoptosis of annulus fibrosus （AF） cell induced by intedeukin-1β （IL-1β）. Methods Cultured AF cells were divided into 6 groups and treated with no drug, 10 ng/mL IL-6, 10 ng/mL IL-1β, 10 ng/mL IL-1β and Z-VAD-FMK （ a caspase-9 inhibitor）, 10 ng/mL IL-1β and 10 ng/mL IL-6, 10 ng/mL IL-1β and 100 ng/mL IL-6, respectively. After three days of culture, the apoptosis rate, the positive rates of caspase-3, -8, and -9 of AF cells were detected with flow cytometry. Results The apoptosis rates of cells in group 1 to 6 were 2.67% ± 1.08%, 2.71% ± 0.53%, 20. 37% ± 1.57 %, 11.34% ± 0.67 %, 18.17 % ± 0.74%, and 9.42 % ± 1.08 %, respectively. There was no significant difference between group 1 and 2, while the apoptosis rates of group 4, 5, and 6 were significantly lower than group 3 （ P = 0. 001, P =0. 172, and P =0. 001, respectively）. Positive rates of caspase-3 in group 5 （ 12. 35% ±0.64% ） and 6 （9.26% ±0. 36% ） were significantly lower than group 3 （ 17.14% ±0. 72% ; P =0. 001 and P 〈0.001, respectively）. And positive rates of caspase-9 in group 5 （ 15.13% ± 1.45% ） and 6 （ 10.17% ± 2.50% ） were significantly lower than group 3 （ 19.4% ±0.98% ; P =0. 014 and P =0. 004, respectively）. But there was not obvious change of caspase-8 activity after IL-6 was added. Conclusion IL-6 is capable of protecting AF cells from IL-1β induced apoptosis in vitro. Mechanism of the protection is related with the inhibition of caspase-3 and -9 activities.展开更多
Objective To observe the seasonal changes in serum levels of interleukin-1 beta(IL-1β), interleukin-6(IL-6) and melatonin(MT) in Bizheng rat model, and explore the relationship between MT and the pathogenesis of rheu...Objective To observe the seasonal changes in serum levels of interleukin-1 beta(IL-1β), interleukin-6(IL-6) and melatonin(MT) in Bizheng rat model, and explore the relationship between MT and the pathogenesis of rheumatoid arthritis. Methods One hundred and sixty Sprague-Dawley rats were randomly divided into four groups in summer(n=80) and winter(n=80) respectively: normal group, collagen-induced arthritis(CIA) model group, operation group, and sham-operation group(n=20 in each group). The CIA model group was injected with collagen emulsion at the base of the tail to induce arthritis. The rats in the operation group received pineal gland resection, and 7 days after the first operation, underwent testectomy or oophorectomy. The rats in the sham-operation group were operated to ligature the sagittal sinus, without extracting the pineal gland. After the operations, the operation group and the sham-operation group both were immunized as the CIA group was. The serum levels of IL-1β, IL-6 and MT in different groups were measured by radioimmunoassay. Results Compared with the normal group, the serum levels of IL-1β and IL-6 increased in the CIA model, operation, and sham-operation groups both in summer and in winter(IL-1β in summer, P=0.008, P<0.01, P=0.012; IL-1β in winter, P=0.019, P<0.01, P=0.027; IL-6 in summer, P=0.028, P<0.01, P=0.024; IL-6 in winter, P=0.006, P<0.01, P=0.008). In the operation group, the serum levels of IL-1β and IL-6 in winter were higher than in summer, but with no statistically significant differences(P=0.844, 0.679). Compared with the normal group, the serum level of MT significantly increased in summer and winter in both the CIA model group(P=0.002, 0.008) and the sham-operation group(P=0.003, 0.007), while significantly decreased in the operation group(P=0.023, 0.003). There was no significant difference in MT level in the operation group between summer and winter(P=0.947). Conclusions The increase of serum levels of IL-1β and IL-6 may exacerbate the inflammatoryreaction and cause a more severe condition in the rheumatoid arthritis. The concentrations of IL-1β, IL-6, and MT correspond with the change of seasons, confirming that there are connections between nature and human body.展开更多
Platichthys stellatus is an economically important marine bony fish species that is cultured in China on a large scale.However,very little is known about its immune-related genes.In this study,the transcriptome of the...Platichthys stellatus is an economically important marine bony fish species that is cultured in China on a large scale.However,very little is known about its immune-related genes.In this study,the transcriptome of the immune organs ofP.stellatus that were intraperitoneally challenged with the pathogen Edwardsiella ictaluri JCM1680 is analyzed.Total RNA from four tissues(spleen,kidney,liver,and intestine) was mixed equally and then sequenced on an Illumina HiSeq 2000 platform.Overall,28 465 813 quality reads were generated and assembled into 43 061 unigenes.Similarity searches against public protein sequence databases were used to annotate 28 291 unigenes(65.7%of the total),368 of which were associated with immunoregulation,including 188 related to immunity response.Additionally,the transcript levels of immunity response unigenes annotated as related to tumor necrosis factor(TNF),TNF receptor,chemokine,major histocompatibility complex,and interleukin-6 were investigated in the different tissues of normal and infected P.stellatus by real-time quantitative PCR.The results confirmed that the unigenes identified in the transcriptome database were indeed expressed and up-regulated in infected P.stellatus.To our knowledge,this is the first report of the sequencing and analysis of the transcriptome of P.stellatus.These findings provide insights into the transcriptomics and immunogenetics of bony fish.展开更多
Objective： To investigate whether remifentanil induced cardioprotecting effect is associated with expression of toll-like receptor 4 （TLR4）, nuclear factor rB （NF-r.B） and serum interleukin -6 （IL-6）. Methods：...Objective： To investigate whether remifentanil induced cardioprotecting effect is associated with expression of toll-like receptor 4 （TLR4）, nuclear factor rB （NF-r.B） and serum interleukin -6 （IL-6）. Methods： Fifty rabbits were randomly divided into 5 groups （n=10） according to the treatment： sham operation group （group A）, ischemla-reperfusion group （group B）, low-dose remifentanil group （group C）, mediate-dose remifentanil group （group D）, and high-dose remlfentanil group （group E） Myocardial TLR4 mRNA levels, NF-r.B protein expression and serum levels of IL-6 were observed in 120 min after reperfusion. Results： The myocardial expressions of TLR4 mRNA, NF-rd3 protein and IL-6 level in sera of groups B, C, D and E were elevated compared with group A. However, remifentanil significantly reduced the levels of TLR4 mRNA, NF- r.B protein expression and serum IL-6 in groups C, D and E compared with group B. There were remarkable differences between the groups （P〈O.O1）. Conclusion： Intravenous remifentanil has protective effect against rabbit myocardial ischemia/reperfusion injury. This effect may be associated with TLR4, NF-r.B expressions on myocytes and serum level of IL-6 in a dose-dependent manner展开更多
The effects of CH925, a novel immune modulator, on hepadna virus infection was evaluated. Day-old ducklings were inoculated intravenously with LJ-76 DHBV containing serum. Infected ducklings were then treated with the...The effects of CH925, a novel immune modulator, on hepadna virus infection was evaluated. Day-old ducklings were inoculated intravenously with LJ-76 DHBV containing serum. Infected ducklings were then treated with the CH925 and the mixture of IL-2 and IL-6 intravenously and the control ducklings received equivalent normal saline (NS). Blood and liver samples were taken and assayed for DHBV DNA and /or DHBsAg. At the completion of the experiment there was a inhibition of viremia with the CH925 and IL-2 + IL-6. Serum DHBV DNA was detected in 6 of 10 ducks in 100 000 unit/kg dosage group, 7 of 10 ducks in 50 000 unit/kg dosage group and 6 of 10 ducks in IL-2 + IL-6 dosage group, compared with 9 of 10 NS control, and it showed a similar result in circulating DHBsAg. When samples of liver DNA were processed for hybridization, a little difference in the DHBV DNA replication was noted between ducks receiving CH925, IL-2 + IL-6 or NS placebo. It is suggested that CH925 might be a potential remedy in HBV infection treatment.展开更多
文摘目的研究骨转换标志物及其与总前列腺特异抗原(total prostate specific antigen,tPSA)、白细胞介素⁃6(interleukin⁃6,IL⁃6)构建的预测模型在前列腺癌骨转移中的临床应用价值。方法比较分析骨钙素(N⁃MID osteocalcin,Osteocalcin)、总I型前胶原氨基末端肽(total procollagen type 1 amino⁃terminal pro⁃peptide,TPINP)、β⁃异构化的C⁃端肽I型胶原片段(β⁃CrossLaps,β⁃CTx)、tPSA、IL⁃6在发生和未发生骨转移的前列腺癌患者血清中的表达差异;运用logistic回归分析,从上述血清标志物中筛选出前列腺癌骨转移的危险因素。并通过筛选的危险因素,构建前列腺癌骨转移的预测模型,进一步绘制ROC曲线评估该预测模型在前列腺癌骨转移中的诊断效能。结果Osteocalcin、TPINP、β⁃CTx及tPSA、IL⁃6在前列腺癌骨转移患者中的表达水平均显著高于未发生骨转移患者(P<0.05);其中Osteocalcin、TPINP、tPSA、IL⁃6为前列腺癌骨转移的独立危险因素(OR=1.088、1.021、1.037、1.415,P<0.05);通过上述危险因素构建的预测模型为logit(P)=(-5.058)+0.085×(Osteocalcin)+0.020×(TPINP)+0.037×(tPSA)+0.347×(IL⁃6),该模型在前列腺癌骨转移诊断中的曲线下面积(AUC)=0.908(P<0.001)。结论前列腺癌骨转移患者存在异常的骨代谢;且由Osteocalcin、TPINP、tPSA、IL⁃6构建的数学模型能够较好地预测前列腺癌骨转移的发生。
文摘Recombinant E.coli JM109, containing pHZ1818 plasmid which included the fused gene encoding human interleukin 6(IL 6), expressed a fusion protein with glutathion S transferase(GST). The fusion protein existed both in the supernatant and inside the bacterial cell,but the insoluble protein had no biological activity and could not be refolded. The rotative speed of the shaker and the temperature of induction were optimized to maximize the expression of the soluble fusion protein. From the supernatant of the cell sonicates Glutathion Sephrose 4B affinity column chromatography was employed to isolate the fusion protein which could be purified to >80 0 0 in a single step. The yield of soluble GST IL 6 was about 10 mg per liter culture. The GST was site specifically cloven by 6 hours of treatment with thrombin and from the thrombin digest mixture IL 6 was purified by Q high performance ion exchange chromatography. From 1 liter of E.coli culture 2 mg refined IL 6 was obtained. The purified IL 6 had a purity of more than 95 0 0 and a biological activity of 1.02×10 8 IU/mg.
文摘The tumor microenvironment （TME） plays a prominent role in the growth of tumor cells. As the major inflammatory component of the TME, M2d macrophages are educated by the TME such that they adopt an immunosnppressive role that promotes tumor metastasis and progression. Fra-1 forms activator protein-1 heterodimers with Jun partners and drives gene transcription. Fra-1 is thought to drastically induce tumorigenesis and progression. However, the functional role of Fra-1 in the generation of M2d macrophages is poorly understood to date. Here, we demonstrate that 4T1 mammary carcinoma cells, when co-cultured with RAW264.7 macrophage cells, skew the RAW264.7 macrophage cell differentiation into M2d macrophages. The 4T1 cells stimulate de novo overexpression of Fra-1 in RAW264.7 cells, and then Fra-1 binds to the interleukin 6 （IL-6） promoter to increase the production of the cytokine IL-6 in RAW264.7 cells. IL-6 acts in an autocrine fashion to skew RAW264.7 macrophage cell differentiation into M2d macrophages. These findings open new insights into how to reverse M2d macrophage-induced immune tolerance to improve the efficacy of immunotherapeutic approaches.
文摘AIM:The current study was to determine the serum/pLasma levels of VEGF,IL-6,malondialdehyde (MDA),nitric oxide (NO),PCT and CRP in gastric carcinoma and correlation with the stages of the disease and accompanying infection. METHODS:We examined the levels of serum VEGF,IL-6, PCT,CRP and plasma MDA,NO in 42 preoperative gastric cancer patients and 23 healthy subjects.There were infection anamneses that had no definite origin in 19 cancer patients. RESULTS:The VEGF levels (mean±SD; pg/mL) were 478.05±178.29 and 473.85±131.24 in gastric cancer patients with and without infection,respectively,and these values were not significantly different (P>0.05).The levels of VEGF, CRP,PCT,It-6,MDA and NO in cancer patients were significantly higher than those in healthy controls and the levels of CRP,PCT,It-6,MDA and NO were statistically increased in infection group when compared with non- infection group (P<0.001). CONCLUSION:Although serum VEGF concentrations were increased in gastric cancer,this increase might not be related to infection.CRP,PCT,IL-6,MDA and NO have obvious drawbacks in the diagnosis of infections in cancer patients. These markers may not help to identify infections in the primary evaluation of cancer patients and hence to avoid unnecessary antibiotic treatments as well as hospitalization. According to the results of this study,IL-6,MDA,NO and especially VEGF can be used as useful parameters to diagnose and grade gastric cancer.
基金Supported by: grant from Ministero dell'Istruzione, dell'Universita e della Ricerca year 2004 (to GM)
文摘AIM： To evaluate the immunohistochemical localization of interleukin-6 （IL-6） and IL-6 receptor （IL-6R） on tumor tissue specimens from patients with hepatocellular carcinoma （HCC） and the serum levels of IL-6 and sIL-6R in a group of patients with HCC as well as liver cirrhosis （LC） in a group of patients with LC alone and in a control group. METHODS： Three groups of subjects were studied： group Ⅰ （n =83） suffering from HCC and LC, group Ⅱ （n = 72） suffering from LC alone and group Ⅲ （n =42） as healthy controls. All patients had hepatitis C virus infection. Serum IL-6 and IL-6R levels were determined using a commercially available ELISA kit. Immunohistochemistry was performed using the streptavidin-biotin complex and rabbit polyclonal antibodies against IL-6 and IL-6R. RESULTS： Immunohistochemistry analysis showed a medium to strong cytoplasmic and membrane reactivity for IL-6 and IL-6R respectively, in at least 40% of cases of HCC, whereas liver cirrhosis patients and controls were negative for IL-6 or showed a very mild and focal dot-like cytoplasmic reaction for IL-6R. Serum IL-6 levels in HCC group were significantly higher than those in LC and control groups （P〈 0.0001）. There was no significant difference in sIL-6R concentrations among 3 groups. When the patients with HCC were divided into groups according to Okuda＇s classification, a significant serum increase of IL-6 and slL-6R level was observed from stage Ⅰ to stage Ⅲ （P〈0.02, P〈0.0005）. When HCC and LC patients were divided into 3 classes of cirrhosis severity according to Child-Pugh, values in HCC patients were significantly higher than those in LC patients for each corresponding class （P〈 0.01）. CONCLUSION： IL-6 serum levels in HCC patients are higher than those in LC patients and controls, suggesting an increased production of this cytokine by neoplastic cells, sIL-6R values are similar in all groups, increasing only in stage III HCC patients. These data suggest that they have a closer relationship with the neoplastic mass rather than with the residual functioning hepatic mass.
基金Supported by A grant from the Doctoral Program of China Medical University
文摘AIM： To investigate the correlation between the expression levels of interleukin （IL）-6 and proteins in tight junctions （TJs） in the esophageal mucosa of rats modeling different types of reflux esophagitis （RE）, and the ability of aluminum phosphate to protect against RE-induced mucosal damage via these proteins. METHODS： Male SPF Wistar rats aged 56 d were divided randomly into acid RE, alkaline RE, mixed RE, and control groups. Various surgical procedures were performed to establish rat models of acid RE. At 14 d after the procedure, some of the rats started aluminum phosphate treatment. Transmission electron microscopy （TEM） was used to observe the morphological features of TJs and desmosomes in the esophageal epithelium. Immunohistochemical methods and Western blotting were used to measure expression of claudin 1, occludin, ZO-1, JAM-l, DSG-1 and IL-6; reverse transcription polymerase chain reaction （RT- PCR） was used to measure expression of mRNA of claudin 1, occludin, ZO-1, JAM-1, DSG-1 and IL-6. RESULTS： At day 14 alter the procedures, an RE model was established in all subsequently sacrificed rats of groups A, B and C. By both gross and microscopic observation, the mucosa was damaged and thickened as the disease progressed. With TEM observation, a widened intercellular space was noticed, with significantly fewer desmosomes. Immunohistochemistry showed significantly higher levels of all proteins in all RE models compared to control rats at 3 d after operation （65.5% ± 25.6% vs 20.5% ± 2.1%, P 〈 0.05, respectively）. At 14 d after operation, along with continuing hyperplasia in the basal layer, the expression of TJ proteins in individual cells gradually decreased （12.4% ± 2.1% vs 20.5% ± 2.1%, P 〈 0.05, respectively）. Western blottings and RT-PCR showed a directly proportional increase in IL-6 levels in relation to TJ proteins, as compared to controls （0.878 ± 0.024 vs 0.205 ± 0.021 and 0.898±0.022 vs 0.205 ± 0.021, P 〈 0.05, respectively）. Upon treatment with aluminum phosphate, however, these protein levels were restored to normal gradually over 30-60 d in rats with acid RE （30.4% ± 2.1% vs 20.5% ± 2.1%, P 〉 0.05, treated vs untreated, respectively）. These levels increased in the rat with alkaline RE, and this increase was accompanied by continued hyperplasia in comparison with controls （85.5% ± 25.6% vs 20.5% ± 2.1%, P 〈 0.05, respectively）. Furthermore, the expression of TJ proteins was not correlated significantly with that of IL-6 in this group. CONCLUSION： These findings indicate that TJ proteins are highly expressed as an early molecular event involved in RE development, and that IL-6 is an inflammatory factor in this process,
基金Supported by a Research Grant from the National Science Council,Taipei, Taiwan, No. NSC91-2314-B002-245
文摘AIM： To evaluate whether the effect of Gin dipeptideenriched total parenteral nutrition （TPN） on postoperative cytokine alteration depended on the disease severity of surgical patients. METHODS： Forty-eight patients with major abdominal surgery were allocated to two groups to receive isonitrogenous （0.228 g nitrogen/kg per d） and isocaloric （30 kcal/kg per d） TPN for 6 d. Control group （Cony） using conventional TPN solution received 1.5 g amino acids/kg per day, whereas the test group received 0.972 g amino acids/kg per day and 0.417 g L-alanyI-L-glutamine （Ala-GIn）/kg per day. Blood samples were collected on d 1 and d 6 postoperatively for plasma interleukin （IL）-2, IL-6, IL-8, and interferon （IFN）-γ analysis. RESULTS： Plasma IL-2 and IFN-γ were not detectable. IL-6 concentrations were significantly lower on the 6^th postoperative day in the Ala-GIn group than those in the Cony group in patients with APACHE Ⅱ≤6, whereas no difference was noted in patients with APACHE Ⅱ〉6. There was no difference in IL-8 levels between the two groups. No difference in cumulative nitrogen balance was observed on d 2-5 after the operation between the two groups （Ala-GIn -3.2±1.6 g vs Cony -6.5±2.7 g）. A significant inverse correlation was noted between plasma IL-6 levels and cumulative nitrogen balance postoperatively in the Ala-GIn group, whereas no such correlation was observed in the Conv group. CONCLUSION： TPN supplemented with Gin dipeptide had no effect on plasma IL-8 levels after surgery. However, Gin supplementation had a beneficial effect on decreasing systemic IL-6 production after surgery in patients with low admission illness severity, and lower plasma IL-6 may improve nitrogen balance in patients with abdominal surgery when Gin was administered.
基金Supported by a grant from National Sciences Foundation of HubeiProvince (2004ABA193).
文摘Objective To investigate the effect of interleukin-6 （ IL-6 ） on the apoptosis of annulus fibrosus （AF） cell induced by intedeukin-1β （IL-1β）. Methods Cultured AF cells were divided into 6 groups and treated with no drug, 10 ng/mL IL-6, 10 ng/mL IL-1β, 10 ng/mL IL-1β and Z-VAD-FMK （ a caspase-9 inhibitor）, 10 ng/mL IL-1β and 10 ng/mL IL-6, 10 ng/mL IL-1β and 100 ng/mL IL-6, respectively. After three days of culture, the apoptosis rate, the positive rates of caspase-3, -8, and -9 of AF cells were detected with flow cytometry. Results The apoptosis rates of cells in group 1 to 6 were 2.67% ± 1.08%, 2.71% ± 0.53%, 20. 37% ± 1.57 %, 11.34% ± 0.67 %, 18.17 % ± 0.74%, and 9.42 % ± 1.08 %, respectively. There was no significant difference between group 1 and 2, while the apoptosis rates of group 4, 5, and 6 were significantly lower than group 3 （ P = 0. 001, P =0. 172, and P =0. 001, respectively）. Positive rates of caspase-3 in group 5 （ 12. 35% ±0.64% ） and 6 （9.26% ±0. 36% ） were significantly lower than group 3 （ 17.14% ±0. 72% ; P =0. 001 and P 〈0.001, respectively）. And positive rates of caspase-9 in group 5 （ 15.13% ± 1.45% ） and 6 （ 10.17% ± 2.50% ） were significantly lower than group 3 （ 19.4% ±0.98% ; P =0. 014 and P =0. 004, respectively）. But there was not obvious change of caspase-8 activity after IL-6 was added. Conclusion IL-6 is capable of protecting AF cells from IL-1β induced apoptosis in vitro. Mechanism of the protection is related with the inhibition of caspase-3 and -9 activities.
基金Supported by the Autonomous Subject of Beijing University of Chinese Medicine(JYB22)the Gasification Theory Innovation Team Funding of Beijing University of Chinese Medicine(JS011)
文摘Objective To observe the seasonal changes in serum levels of interleukin-1 beta(IL-1β), interleukin-6(IL-6) and melatonin(MT) in Bizheng rat model, and explore the relationship between MT and the pathogenesis of rheumatoid arthritis. Methods One hundred and sixty Sprague-Dawley rats were randomly divided into four groups in summer(n=80) and winter(n=80) respectively: normal group, collagen-induced arthritis(CIA) model group, operation group, and sham-operation group(n=20 in each group). The CIA model group was injected with collagen emulsion at the base of the tail to induce arthritis. The rats in the operation group received pineal gland resection, and 7 days after the first operation, underwent testectomy or oophorectomy. The rats in the sham-operation group were operated to ligature the sagittal sinus, without extracting the pineal gland. After the operations, the operation group and the sham-operation group both were immunized as the CIA group was. The serum levels of IL-1β, IL-6 and MT in different groups were measured by radioimmunoassay. Results Compared with the normal group, the serum levels of IL-1β and IL-6 increased in the CIA model, operation, and sham-operation groups both in summer and in winter(IL-1β in summer, P=0.008, P<0.01, P=0.012; IL-1β in winter, P=0.019, P<0.01, P=0.027; IL-6 in summer, P=0.028, P<0.01, P=0.024; IL-6 in winter, P=0.006, P<0.01, P=0.008). In the operation group, the serum levels of IL-1β and IL-6 in winter were higher than in summer, but with no statistically significant differences(P=0.844, 0.679). Compared with the normal group, the serum level of MT significantly increased in summer and winter in both the CIA model group(P=0.002, 0.008) and the sham-operation group(P=0.003, 0.007), while significantly decreased in the operation group(P=0.023, 0.003). There was no significant difference in MT level in the operation group between summer and winter(P=0.947). Conclusions The increase of serum levels of IL-1β and IL-6 may exacerbate the inflammatoryreaction and cause a more severe condition in the rheumatoid arthritis. The concentrations of IL-1β, IL-6, and MT correspond with the change of seasons, confirming that there are connections between nature and human body.
基金Supported by the National High Technology Research and Development Program of China(863 Program)(Nos.2012AA10A413,2012AA10A408)the National Marine Public Welfare Research Project(No.201205025)
文摘Platichthys stellatus is an economically important marine bony fish species that is cultured in China on a large scale.However,very little is known about its immune-related genes.In this study,the transcriptome of the immune organs ofP.stellatus that were intraperitoneally challenged with the pathogen Edwardsiella ictaluri JCM1680 is analyzed.Total RNA from four tissues(spleen,kidney,liver,and intestine) was mixed equally and then sequenced on an Illumina HiSeq 2000 platform.Overall,28 465 813 quality reads were generated and assembled into 43 061 unigenes.Similarity searches against public protein sequence databases were used to annotate 28 291 unigenes(65.7%of the total),368 of which were associated with immunoregulation,including 188 related to immunity response.Additionally,the transcript levels of immunity response unigenes annotated as related to tumor necrosis factor(TNF),TNF receptor,chemokine,major histocompatibility complex,and interleukin-6 were investigated in the different tissues of normal and infected P.stellatus by real-time quantitative PCR.The results confirmed that the unigenes identified in the transcriptome database were indeed expressed and up-regulated in infected P.stellatus.To our knowledge,this is the first report of the sequencing and analysis of the transcriptome of P.stellatus.These findings provide insights into the transcriptomics and immunogenetics of bony fish.
基金Supported by Shaanxi Provincial Scientific and Technological Research Projects (2008K13-02)
文摘Objective： To investigate whether remifentanil induced cardioprotecting effect is associated with expression of toll-like receptor 4 （TLR4）, nuclear factor rB （NF-r.B） and serum interleukin -6 （IL-6）. Methods： Fifty rabbits were randomly divided into 5 groups （n=10） according to the treatment： sham operation group （group A）, ischemla-reperfusion group （group B）, low-dose remifentanil group （group C）, mediate-dose remifentanil group （group D）, and high-dose remlfentanil group （group E） Myocardial TLR4 mRNA levels, NF-r.B protein expression and serum levels of IL-6 were observed in 120 min after reperfusion. Results： The myocardial expressions of TLR4 mRNA, NF-rd3 protein and IL-6 level in sera of groups B, C, D and E were elevated compared with group A. However, remifentanil significantly reduced the levels of TLR4 mRNA, NF- r.B protein expression and serum IL-6 in groups C, D and E compared with group B. There were remarkable differences between the groups （P〈O.O1）. Conclusion： Intravenous remifentanil has protective effect against rabbit myocardial ischemia/reperfusion injury. This effect may be associated with TLR4, NF-r.B expressions on myocytes and serum level of IL-6 in a dose-dependent manner
文摘The effects of CH925, a novel immune modulator, on hepadna virus infection was evaluated. Day-old ducklings were inoculated intravenously with LJ-76 DHBV containing serum. Infected ducklings were then treated with the CH925 and the mixture of IL-2 and IL-6 intravenously and the control ducklings received equivalent normal saline (NS). Blood and liver samples were taken and assayed for DHBV DNA and /or DHBsAg. At the completion of the experiment there was a inhibition of viremia with the CH925 and IL-2 + IL-6. Serum DHBV DNA was detected in 6 of 10 ducks in 100 000 unit/kg dosage group, 7 of 10 ducks in 50 000 unit/kg dosage group and 6 of 10 ducks in IL-2 + IL-6 dosage group, compared with 9 of 10 NS control, and it showed a similar result in circulating DHBsAg. When samples of liver DNA were processed for hybridization, a little difference in the DHBV DNA replication was noted between ducks receiving CH925, IL-2 + IL-6 or NS placebo. It is suggested that CH925 might be a potential remedy in HBV infection treatment.
