地塞米松对人外周血单核细胞核因子-κB活化和肿瘤坏死因子-α释放的影响

目的探讨地塞米松(dexamethasone,DXM)对脂多糖(lipopolysaccharide,LPS)诱导的人外周血单核细胞核因子(nuclear factor kappaB,NF-κB)活化和肿瘤坏死因子(tumor necrosis factor-α,TNF-α)产生的影响。方法收集人外周血单核细胞接种于培养板后,分生理盐水对照组、LPS组、LPS DXM1μmol/L组、LPS DXM10μmol/L组。LPS诱导0、0.5、2、6、12、16h后留取细胞及细胞培养上清。采用免疫细胞化学染色法检测细胞NF-κBp65阳性表达率,酶联免疫吸附法检测细胞培养上清中TNF-α的含量。结果LPS诱导0.5h后NF-κB表达开始增加,2h达高峰。2h时TNF-α合成开始增加,6h达高峰。在2、6、12h时,LPS DXM1μmol/L组和10μmol/L组TNF-α含量均比LPS组各相应时间点低(P<0.05或0.01)。在0.5、2、6h时LPS DXM1μmol/L组NF-κB阳性表达率和在2、6h时LPS DXM10μmol/L组NF-κB阳性表达率均比LPS组低(P<0.05或0.01)。LPS DXM1μmol/L和10μmol/L组NF-κB阳性表达率和TNF-α含量在各时间点差异均无统计学意义。结论LPS在体外诱导人外周血单核细胞NF-κB的活化和TNF-α的产生;DXM通过抑制NF-κB的活化和TNF-α的释放而发挥抗炎作用,并且这种抑制效应可能不随剂量的增加而增强。     

核因子-κB对急性胰腺炎时肿瘤坏死因子-αmRNA表达的调控

目的观察急性胰腺炎(acutepancreatitis,AP)发生时胰腺组织中核因子κB(NFκB)对肿瘤坏死因子αmRNA表达的调控作用。方法Wistar大鼠64只,随机均分为AP组和对照组,AP组以蛙皮素(Caerulein)腹腔内注射制成AP模型。分别于12h、24h、36h、72h后处死实验动物,用流式细胞术(FCM)检测NFκB激活水平,用半定量RTPCR检测TNFαmRNA的表达水平,并分析二者之间的相关性。结果AP组的NFκB激活及TNFαmRNA表达水平在各时间点均显著高于同时段对照组的水平(P<0.01),二者之间具有相关性(P<0.05)。结论AP发生时,胰腺组织中NFκB高度活化,促进了TNFαmRNA的表达,从而加重了胰腺的损伤。     

Gabexate mesilate,a synthetic protease inhibitor,inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production by inhibiting activation of both nuclear factor-kappaB and activator protein-1 in human monocytes

Gabexate mesilate, a synthetic protease inhibitor, was shown to be effective in treating patients with sepsis-associated disseminated intravascular coagulation in which tumor necrosis factor-alpha (TNF-alpha) plays a critical role. We demonstrated that gabexate mesilate reduced lipopolysaccharide (LPS)-induced tissue injury by inhibiting TNF-alpha production in rats. In the present study, we analyzed the mechanism(s) by which gabexate mesilate inhibits LPS-induced TNF-alpha production in human monocytes in vitro. Gabexate mesilate inhibited the production of TNF-alpha in monocytes stimulated with LPS. Gabexate mesilate inhibited both the binding of nuclear factor-kappaB (NF-kappaB) to target sites and the degradation of inhibitory kappaBalpha. Gabexate mesilate also inhibited both the binding of activator protein-1 (AP-1) to target sites and the activation of mitogen-activated protein kinase pathways. These observations strongly suggest that gabexate mesilate inhibited LPS-induced TNF-alpha production in human monocytes by inhibiting activation of both NF-kappaB and AP-1. Inhibition of TNF-alpha production by gabexate mesilate might explain at least partly its therapeutic effects in animals given LPS and those in patients with sepsis.     

The production of tumor necrosis factor-alpha by rat basophilic leukemia cells with triggering IgE receptor

We evaluated cytotoxic factor released from rat basophilic leukemia cells (RBL) sensitized with anti-ovalbumin (OVA) mouse serum after incubation with OVA. The cytotoxic activity of this factor was completely blocked by anti-mouse tumor necrosis factor-alpha (mTNF-alpha) specific antibody. Therefore, we concluded that by triggering the IgE receptor, RBL could produce and release TNF-alpha.     

4-hydroxynonenal decreases interleukin-6 expression and protein production in primary rat Kupffer cells by inhibiting nuclear factor-kappaB activation

Kupffer cells have been documented to play an important role in the early events of liver injury and regeneration by releasing biologically active mediators such as interleukin-6 (IL-6). 4-Hydroxy-trans-2-nonenal (4-HNE), a major end product of lipid peroxidation, has multiple cytotoxic effects and is implicated in chemical-induced liver injury. Consequently, the purpose of this study was to evaluate the ability of 4-HNE to modulate IL-6 production in isolated primary rat Kupffer cells. 4-HNE (0.1-10 microM) reduced both lipopolysaccharide (LPS)-induced IL-6 protein production and mRNA levels. The role of nuclear factor-kappaB (NF-kappaB) in IL-6 induction was elucidated using Kupffer cells transduced in vitro with a recombinant adenovirus containing a IkappaBalpha super-repressor resistant to phosphorylation and degradation (Ad5IkappaB). Using this system, LPS-induced IL-6 protein production was inhibited by 65% in Ad5IkappaB-infected cells. The treatment of Kupffer cells for 1 h with 4-HNE followed by stimulation for 1 h with LPS (500 ng/ml) resulted in a concentration-dependent decrease in NF-kappaB activation. Similarly, decreased NF-kappaB activity in these cells paralleled a reduction in IkappaBalpha mRNA levels. Furthermore, upon LPS stimulation, 4-HNE stabilized IkappaBalpha, which corresponded to a decrease in phosphorylated IkappaBalpha. At lower 4-HNE concentrations (0-5 microM), interactions between p65 and IkappaBalpha proteins were maintained as detected by immunoprecipitation-immunoblot analyses. In conclusion, these data suggest that 4-HNE inhibits IL-6 production in rat Kupffer cells by preventing activation of the NF-kappaB pathway and suppressing IkappaBalpha phosphorylation. These results have functional implications in that 4-HNE may interfere with the ability of Kupffer cells to produce cytokines proposed to play an important role in liver regeneration.     

Biliary pancreatitis-associated ascitic fluid activates the production of tumor necrosis factor-alpha in acinar cells

OBJECTIVE: Acute pancreatitis is associated with increased cytokine release from different cell sources. We have investigated the ability of acinar cells, in comparison with inflammatory peripheral blood cells, to produce tumor necrosis factor (TNF)-alpha in response to pancreatitis-associated ascitic fluid (PAAF). DESIGN: Controlled, randomized animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Flow cytometry using phycoerythrin-labeled monoclonal anti-TNF-alpha antiserum. MEASUREMENTS AND MAIN RESULTS: PAAF (20%, v:v) obtained from rats with acute pancreatitis induced by bile-pancreatic duct obstruction significantly increased TNF-alpha production in acinar cells, as measured by flow cytometry using phycoerythrin-labeled monoclonal anti-TNF-alpha antiserum. Neither heating of PAAF nor the addition of soybean trypsin inhibitor or neutralizing amounts of anti-TNF-alpha monoclonal antiserum reduced the acinar cell TNF-alpha production. Monocytes and lymphocytes did not produce TNF-alpha in response to PAAF. Likewise, the typical monocyte and lymphocyte stimulating factors-lipopolysaccharide (10 microg/microL) and phorbol 12-myristate 13-acetate (250 ng/mL) plus ionomycin (1 microg/mL), respectively-were not able to produce TNF-alpha in acinar cells. By comparison of the two acinar cell populations differentiated by flow cytometry, R2 cells (with higher forward scatter values) showed a greater ability to produce TNF-alpha in response to PAAF than R1 cells. Acinar cell nuclear factor-kappaB was activated, but TNF-alpha production was not totally inhibited in presence of N-acetyl cysteine (30, 100 mM). CONCLUSIONS: The production of TNF-alpha from different cell sources is selectively activated. PAAF may be involved in the pathophysiology of acute pancreatitis by TNF-alpha production in acinar cells through mechanisms partially mediated by nuclear factor-kappaB activation. PAAF components, such as TNF-alpha or trypsin, are not responsible for acinar cell activation. TNF-alpha was induced by heat-resistant PAAF factors, displaying acinar cells with higher forward scatter (R2) a greater ability to increase the TNF-alpha production than R1 cells.     

Effects of tumor necrosis factor-alpha on the in vitro maturation of tumor-reactive effector T cells

Culture methods that enhance the anti-tumor reactivity of primed T cells would be important in adoptive immunotherapy of cancer. Using several different syngeneic murine tumor models, the authors evaluated the effects of tumor necrosis factor-alpha (TNF-alpha) exposure on tumor-draining lymph node (TDLN) cells during in vitro activation. Mice were inoculated with weakly immunogenic (i.e., MCA 205, MCA 207 sarcoma) or the poorly immunogenic (i.e., D5 melanoma) tumor cells, and TDLN cells were harvested 9 or 10 days later for activation by an anti-CD3/interleukin-2 culture procedure. Human recombinant TNF-alpha (25 ng/mL) added during the activation culture resulted in a two-fold increase in interferon-gamma release (type 1 response) and a significant reduction of interleukin-10 (type 2 response) after tumor antigen stimulation. In an adoptive transfer model, TNF-alpha-cultured TDLN cells mediated significantly greater regression of established tumor than did TDLN cells cultured in the absence of TNF-alpha in five of five experiments. Neutralization of interleukin-10 monoclonal antibody further augmented the therapeutic efficacy of TNF-alpha-cultured TDLN cells. These studies document the ability of TNF-alpha to selectively promote a type 1 over a type 2 response in a bulk population of tumor-primed T cells during in vitro activation.     

Defective in vitro production of gamma-interferon and tumor necrosis factor-alpha by circulating T cells from patients with the hyper-immunoglobulin E syndrome.

Circulating T cells from four patients with the hyper-IgE syndrome were found to produce significantly lower concentrations of interferon-gamma (IFN-gamma) in response to stimulation with phytohemagglutinin (PHA) than did T cells from eight age-matched healthy controls, three patients with atopic dermatitis and one patient with chronic granulomatous disease. A clonal analysis revealed that patients with hyper-IgE syndrome had markedly lower proportions of circulating T cells able to produce IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) in comparison with controls. In contrast, the proportions of peripheral blood T cells able to produce IL-4 or IL-2 were not significantly different in patients and controls. All the four patients with hyper-IgE syndrome showed high proportions of circulating CD4+ helper T cells able to induce IgE synthesis in allogeneic B cells, as well. Such an activity for IgE synthesis appeared to be positively correlated with IL-4 production by T cells and inversely related to the ability of the same T cells to produce IFN-gamma. Since IFN-gamma exerts an inhibitory effect on the synthesis of IgE and both IFN-gamma and TNF-alpha play an important role in inflammatory reactions, we suggest that the defective production of IFN-gamma may be responsible for hyperproduction of IgE and the combined defect of IFN-gamma and TNF-alpha may contribute to the undue susceptibility to infections seen in patients with hyper-IgE syndrome.     

Opposite effects of enhanced tumor necrosis factor-alpha production from Kupffer cells by gadolinium chloride on liver injury/mortality in endotoxemia of normal and partially hepatectomized mice

Gadolinium chloride (GdCl3) reportedly inhibits Kupffer cell function including TNF-alpha production and thereby improves organ dysfunctions after LPS challenge, particularly in partially hepatectomized (PH) mice. In addition, TNF-alpha reportedly promotes the regeneration of hepatocytes after PH. However, we have frequently seen GdCl3 treatment increase the mortality of normal mice after LPS injection. Therefore, we investigated this controversial issue in the present study. The mice treated by GdCl3 (10 mg/kg, i.v.) at 24 h before LPS challenge showed increased serum TNF-alpha and ALT levels after LPS challenge and a decreased mouse survival rate. The Kupffer cells from GdCl3-treated mice consistently produced a much larger amount of TNF-alpha following in vitro LPS stimulation than those of the control mice despite the fact that the Kupffer cells decreased in number and also demonstrated decreased superoxide production. Anti-TNF-alpha Ab before LPS-injection greatly improved GdCl3-induced mouse mortality and the degree of liver injury. In marked contrast, the increased amount of TNF-alpha induced by GdCl3 improved the survival after LPS challenge in PH mice because TNF-alpha promoted hepatocyte mitosis/regeneration in PH liver as evidenced by the fact that the inhibition of TNF-alpha before PH suppressed hepatocyte regeneration and decreased survival after LPS challenge. In conclusion, GdCl3 depletes the superoxide-producing Kupffer cells but conversely enhances the function of TNF-alpha-producing Kupffer cells, which thereby leads to LPS-induced mortality. Meanwhile, the increased TNF-alpha production induced by GdCl3 supports liver regeneration and increases the survival after LPS challenge in PH mice.     

急性脑损伤大鼠脑组织核转录因子-κB活性及肿瘤坏死因子-α表达的变化

本研究旨在观察大鼠急性脑损伤后脑组织核转录因子-κB(NF-κB)活性及肿瘤坏死因子-α(TNF—α)蛋白表达的变化，探讨NF-κB活化在脑损伤后继发性脑水肿中的作用；并给应用NF-κB特异性抑制剂吡咯烷二硫基甲酸酯(PDTC)治疗提供佐证。     

八肽胆囊收缩素对肿瘤坏死因子α诱导的大鼠滑膜细胞株RSC-364核因子κΒ活性变化的影响及其受体机制

目的观察硫酸化八肽胆囊收缩素(cholecystokinin octapeptide,CCK-8)对肿瘤坏死因子α诱导大鼠滑膜细胞株RSC-364核因子κB的影响,以及CCK-A/B受体是否参与这一过程.方法实验于2003-02/2004-02在河北医科大学法医学教研室分子生物学实验室完成.取大鼠滑膜细胞株RSC-364经肿瘤坏死因子α(10μg/L)、sCCK-8(10-8,10-7,10-6mol/L)、CCK受体拮抗剂丙谷胺及溶剂单独或联合应用孵育①孵育3 h,用反转录-聚合酶链反应技术检测细胞CCK-A受体及CCK-B受体mRNA的表达.②孵育1 h,用电泳迁移率检测核因子κB相对活性.③孵育30 min,用Western blot检测胞浆IκB蛋白表达的相对水平.结果①细胞CCK-A受体及CCK-B受体mRNA的表达RSC-364细胞固有表达CCK-A/B受体,肿瘤坏死因子α(10 μg/L)可使CCK-A受体和CCK-B受体mRNA的表达分别上调148%和173%(P＜0.01).肿瘤坏死因子α和CCK-8(10-810-6 mol/L)联合孵育细胞,CCK-A受体和CCK-B受体mRNA表达与肿瘤坏死因子α组相比分别增高47%,56%,30%和57%,13%,24%(P＜0.05,0.01).②核因子κB相对活性肿瘤坏死因子α组明显高于对照组(294.45±36.48,0,P＜0.01);肿瘤坏死因子α+CCK-8 10-8,10-7,10-6 mol/L组高于肿瘤坏死因子α组(470.69±56.76,489.37±64.95,558.90±74.15,P＜0.05,0.01);CCK-8的作用可被丙谷胺减弱(400.79±39.06).③IκB蛋白表达的相对水平肿瘤坏死因子α组明显低于对照组(139.43±30.76,220.79±34.58,P＜0.01),肿瘤坏死因子α+CCK-8 10-8,10-7,10-6 mol/L组低于肿瘤坏死因子α组(95.26±8.54,84.15±8.77,63.28±16 13,P＜0.05),并可被丙谷胺所抑制(137.22±20.33,P＜0.01).结论CCK-8对肿瘤坏死因子α诱导的RSC-364核因子κB活性具有正向调节作用,并能降低IκBα蛋白水平,提示CCK-8在类风湿性关节炎发病过程中可能具有调控作用,此作用可能通过滑膜细胞上的CCK受体实现.     

八肽胆囊收缩素对肿瘤坏死因子α诱导的大鼠滑膜细胞株RSC-364核因子κB活性变化的影响及其受体机制

目的:观察硫酸化八肽胆囊收缩素(cholecystokinin octapeptide,CCK-8)对肿瘤坏死因子α诱导大鼠滑膜细胞株RSC-364核因子κB的影响,以及CCK-A/B受体是否参与这一过程。方法:实验于2003-02/2004-02在河北医科大学法医学教研室分子生物学实验室完成。取大鼠滑膜细胞株RSC-364经肿瘤坏死因子α(10 μg/L)、sCCK-8(10-8,10-7,10-6 mol/L)、CCK受体拮抗剂丙谷胺及溶剂单独或联合应用孵育:①孵育3h,用反转录-聚合酶链反应技术检测细胞CCK-A受体及CCK-B受体mRNA的表达。②孵育1h,用电泳迁移率检测核因子κB相对活性。③孵育30 min,用Western blot检测胞浆IκB蛋白表达的相对水平。结果:①细胞CCK-A受体及CCK-B受体mRNA的表达:RSC-364细胞固有表达CCK-A/B受体,肿瘤坏死因子α(10 μg/L)可使CCK-A受体和CCK-B受体mRNA的表达分别上调148%和173%(P<0.01)。肿瘤坏死因子α和CCK-8(10-8～10-6 mol/L)联合孵育细胞,CCK-A受体和CCK-B受体mRNA表达与肿瘤坏死因子α组相比分别增高47%,56%,30%和57%,13%,24%(P<0.05,0.01)。②核因子κB相对活性:肿瘤坏死因子α组明显高于对照组(294.45±36.48,0,P<0.01);肿瘤坏死因子α CCK-810-8,10-7,10-6 mol/L组高于肿瘤坏死因子α组(470.69±56.76,489.37±64.95,558.90±74.15,P<0.05,0.01);CCK-8的作用可被丙谷胺减弱(400.79±39.06)。③IκB蛋白表达的相对水平:肿瘤坏死因子α组明显低于对照组(139.43±30.76,220.79±34.58,P<0.01),肿瘤坏死因子α CCK-810-8,10-7,10-6 mol/L组低于肿瘤坏死因子α组(95.26±8.54,84.15±8.77,63.28±16.13,P<0.05),并可被丙谷胺所抑制(137.22±20.33,P<0.01)。结论:CCK-8对肿瘤坏死因子α诱导的RSC-364核因子κB活性具有正向调节作用,并能降低IκBα蛋白水平,提示CCK-8在类风湿性关节炎发病过程中可能具有调控作用,此作用可能通过滑膜细胞上的CCK受体实现。     

CancerB increases production of nitric oxide and tumor necrosis factor-alpha in peritoneal macrophages

BACKGROUND: CancerB (CCB, IMSF-5), herbal combination, may be able to stimulate potential toxic mediators such as nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) in isolated mouse peritoneal macrophages. METHODS: NO production was determined by Griess method, and TNF-alpha production by enzyme-linked immunosorbent assay. Amounts of proteins were observed by Western blotting. RESULTS: CCB had no effect on NO production by itself, but CCB alone did stimulate the production of TNF-alpha. When CCB was used in combination with recombinant interferon-gamma (rIFN-gamma), there was a marked cooperative induction of NO production, TNF-alpha production and NF-kappa B activation. The increase in NO synthesis was reflected as an increased amount of inducible NO synthase protein. The increased production of NO from rIFN-gamma plus CCB-stimulated peritoneal macrophages was decreased by the treatment with N(G)-monomethyl-L-arginine or N(alpha)-Tosyl-Phe Chloromethyl Ketone. Nuclear factor-kappa B (NF-kappa B) inhibitor, pyrrolidine dithiocarbamate was able to completely inhibit the production of NO and TNF-alpha. CONCLUSIONS: These findings demonstrate that CCB increases the production of NO and TNF-alpha by rIFN-gamma-primed peritoneal macrophages and suggest that NF-kappa B plays a critical role in mediating these effects of CCB.     

核因子κB及其抑制蛋白ⅠκBα在成年大鼠坐骨神经许旺细胞的分布

目的观察核因子κB及其抑制蛋白ⅠκBα在成年大鼠坐骨神经许旺细胞的表达,并分析二者之间的关系及意义.方法实验于2005-01/06在重庆工学院生物工程学院及第三军医大学大坪医院野战外科研究所完成.随机取成年雄性SD大鼠6只,体质量200～250 g.1%戊巴比妥钠(20～40 mg/kg)腹腔麻醉后打开胸腔,用4%多聚甲醛溶液经左心室灌注后,取左侧坐骨神经,采用p65和p50(由p65和p50两个亚基组成的异源二聚体在核因子κB组成中发挥主要功能)及抑制蛋白ⅠκBα的多克隆抗体进行免疫组织化学染色,检测核因子κB及其抑制蛋白ⅠκBα在正常成年大鼠坐骨神经许旺细胞的表达及分布.结果①p65和p50在坐骨神经许旺细胞胞浆中表达均很弱,胞核中则不表达.②ⅠκBα则在胞浆中有较强的表达,胞核中不表达.结论核因子κB及其抑制蛋白ⅠκBα在正常成年大鼠坐骨神许旺细胞经均有一定程度的表达,在胞浆中前者表达较弱,后者较强,二者在胞核中均不表达.     

Histamine inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production in an intercellular adhesion molecule-1- and B7.1-dependent manner

Lipopolysaccharide (LPS) is recognized as a key molecule in the pathogenesis of Gram negative sepsis and septic shock. In the present study, we demonstrate that LPS (1-1000 pg/ml) concentration dependently up-regulated the expression of intercellular adhesion molecule (ICAM)-1, B7.1, and B7.2 on human monocytes using fluorescence-activated cell sorting analysis, and that tumor necrosis factor (TNF)-alpha production induced by LPS in peripheral blood mononuclear cells (PBMCs) was inhibited by the addition of antibodies against these adhesion molecules, suggesting the dependence of TNF-alpha production on cell-cell interaction through these adhesion molecules. Moreover, we found that histamine (10(-7)-10(-4) M) concentration dependently inhibited the expression of ICAM-1 and B7.1, but not B7.2 on monocytes induced by LPS. Histamine also inhibited the responses of TNF-alpha production induced by LPS. The modulatory effects of histamine on ICAM-1 and B7.1 expression and TNF-alpha production were all concentration dependently antagonized by famotidine but not by d-chlorpheniramine and thioperamide, and were mimicked by selective H2-receptor agonists but not by H1-, H3-, and H4-receptor agonists, indicating the involvement of H2-receptors in the histamine action. Dibutyryl cAMP down-regulated ICAM-1 and B7.1 expression on monocytes stimulated by LPS, suggesting the mediation by the cyclic adenosine monophosphate-protein kinase A pathway of H2-receptor activation. These results as a whole indicated that histamine via H2-receptor inhibited the LPS-induced TNF-alpha production through the regulation of ICAM-1 and B7.1 expression, leading to the reduction of innate immune response stimulated by LPS.     

核因子κ Bp65特异性小干涉核糖核酸抑制肿瘤坏死因子α及白细胞介素1β诱导的软骨细胞中基质金属蛋白酶9的表达

背景：小干涉核糖核酸是核糖核酸干涉的起始诱导物，在细胞内引起强烈的核糖核酸干涉，降解目的基因的信使核糖核酸，以控制目的基因表达。目的：利用核因子κBp65特异性小干涉核糖核酸抑制软骨细胞中肿瘤坏死因子α和白细胞介素1β诱导的核因子κB的活性及其基质金属蛋白酶9的表达，观察在软骨细胞中核因子κBp65与细胞因子的关系。设计、时间和地点：单一样本观察．细胞学体外实验，于2006—09／2007—09在北京大学医学部中心实验室完成。材料：SD大鼠关节软骨细胞。方法：利用质脂体将筛选优化好的核因子κBp65特异性小于涉核糖核酸转染软骨细胞，特异性抑制核因子κBp65的表达，继而抑制肿瘤坏死因子α和白细胞介素1β诱导的核因子κB的活性及基质金属蛋白酶9的表达。主要观察指标：利用电泳迁移率试验检测核因子κB的活性，反转录聚合酶链反应和蛋白质免疫印记法分析从信使核糖核酸和蛋白质两水平检测基质金属蛋白酶9的表达。结果：核因子κBp65特异性小干涉核糖核酸抑制核因子κBp65的表达，降低肿瘤坏死因子α和白细胞介素1β诱导的核因子κB的转录活性，抑制肿瘤坏死因子α和白细胞介素1β诱导的基质金属蛋白酶9的表达。 结论：在软骨细胞中核因子κBp65与肿瘤坏死因子α和白细胞介素1β关系密切。     

Augmentation of murine tumor necrosis factor production by amphotericin B in vitro and in vivo.

Murine peritoneal macrophages were preincubated with amphotericin B (AMPH) and were then stimulated with bacterial lipopolysaccharide or streptococcal preparation (OK432). These macrophages produced a large amount of tumor necrosis factor. When administered to mice, the priming activity of amphotericin B for tumor necrosis factor production in vivo was also observed.