苦参碱对体外小鼠脾细胞增殖及腹腔巨噬细胞释放白细胞介素—1…

目的：研究苦参碱对小鼠脾细胞增殖及腹腔巨噬细胞释放白细胞介素－１（ＩＬ－１）及－６（ＩＬ－６）的影响，方法：（＾３Ｈ）ＴｄＲ参入法测定脾细胞增殖，胸腺细胞增殖法和Ｂ９细胞增殖ＭＴＴ法测定ＩＬ－１和ＩＬ－６活性。结果，苦对碱（１２５－５００ｍｇ．Ｌ＾－１）以剂量依赖方式显著抑制ＣｏｎＡ及脂多糖（ＬＰＳ）诱导的小鼠脾细胞增殖心及ＬＰＳ诱导的的小鼠腹腔巨噬细胞释放ＩＬ－２和ＩＬ－６。结论：苦参碱抑制体个     

Inhibitory effects of nitric oxide and interleukin-10 on production of tumor necrosis factorα,interleukin-1β,and interleukin-6 in mouse alveolar macrophages

目的：观察一氧化氮和ＩＬ１０对肺泡巨噬细胞炎症反应的调节作用．方法：小鼠肺泡巨噬细胞（ＡＭ）受脂多糖（ＬＰＳ）１０ｍｇ·Ｌ－１刺激同时,加入一氧化氮合酶抑制剂Ｓ硫酸甲基异硫脲（ＳＭＴ）或一氧化氮供体Ｓ亚硝基乙酰青霉胺（ＳＮＡＰ）．ＥＬＩＳＡ法测定上清液中ＴＮＦα、ＩＬ１β、ＩＬ６和ＩＬ１０浓度．结果：ＡＭ受ＬＰＳ刺激后,ＴＮＦα、ＩＬ１β和ＩＬ６释放峰值分别在６、１２和２４小时．ＳＭＴ抑制一氧化氮释放,但促进ＩＬ１β和ＩＬ６释放,对ＴＮＦα无影响．ＳＮＡＰ对ＩＬ１β和ＩＬ６释放有明显的抑制作用,呈剂量依赖效应．重组ＩＬ１０抑制ＴＮＦα、ＩＬ１β和ＩＬ６释放,而ＩＬ１０单克隆抗体促进上述因子释放．结论：内源及外源性一氧化氮和ＩＬ１０均对ＬＰＳ诱导的炎症性细胞因子释放有抑制作用．     

苦参碱对细菌脂多糖诱导大鼠枯否细胞释放肿瘤坏死因子及白细胞介素-6的影响

目的是研究苦参碱对细菌脂多糖（ｌｉｐｏｐｏｌｙｓａｃｈｒｉｄｅｓ，ＬＰＳ）诱导经卡西霉素（ｃａｌｃｉｍｙｃｉｎ，Ｃａｌ）预激活的大鼠枯否细胞分泌肿瘤坏死因子（ｔｕｍｏｒｎｅｃｒｏｓｉｓｆａｃｔｏｒ，ＴＮＦ）、白细胞介素６（ｉｎｔｅｒｌｅｕｋｉｎ６，ＩＬ６）的影响以及对小鼠体内产生ＴＮＦ和ＩＬ６的影响。结果，苦参碱１２５，２５０及５００ｍｇ·Ｌ－１剂量依赖性抑制大鼠枯否细胞分泌ＴＮＦ和ＩＬ６；苦参碱５０及１００ｍｇ·ｋｇ－１降低小鼠体内ＴＮＦ和ＩＬ６的水平。提示苦参碱的抗炎作用可能与其抑制ＴＮＦ及ＩＬ６的产生有关。     

Ro31—8220抑制纤维蛋白原降解产物诱导的小鼠腹腔巨噬细胞释放？…

目的 研究纤维蛋白原降解产物体外诱导小鼠腹腔巨噬细胞释放白细胞介素－１（ＩＬ－１）及白细胞介素－６（ＩＬ－６）的作用及一种新型蛋白激酶Ｃ（ＰＫＣ）抑制剂Ｒｏ３１－８２２０（Ｒｏ）的影响,方法 胸腺细胞增殖法和Ｂ９细胞增殖ＭＴＴ法测定了ＩＬ－１和ＩＬ－６活性。结果纤维蛋白原降解产物促进小鼠腹腔巨噬释放ＩＬ－１及ＩＬ－６,Ｒｏ（０．０１－１μｍｏｌ．Ｌ＾－１）明显抑制ＩＬ－１及ＩＬ－６的释放,结论：Ｒ     

Effects of indometacin on joint damage in rat and rabbit

目的：研究吲哚美辛（Ｉｎｄ）对关节损伤的影响．方法：检测佐剂性关节炎大鼠（ＡＡ）非致炎侧后足爪容积，ＬＰＳ诱导腹腔巨噬细胞和关节滑膜细胞产生白细胞介素１（ＩＬ１），以及兔滑膜成纤维细胞增殖反应和软骨蛋白多糖的合成．结果：Ｉｎｄ２ｍｇ·ｋｇ－１·ｄ－１ｉｇ９ｄ，可抑制ＡＡ大鼠ｄ１８，ｄ２１，和ｄ２４继发炎症反应，但促进巨噬细胞和滑膜细胞分泌ＩＬ１．Ｉｎｄ１０μｍｏｌ·Ｌ－１体外分别促进ＩＬ１诱导兔滑膜成纤维细胞增殖反应以及抑制关节软骨蛋白多糖合成．结论：Ｉｎｄ不利于关节损伤的修复．     

一氧化氮和白细胞介素—10对小鼠肺泡巨噬细胞产生肿瘤坏死因？…

目的 观察一氧化氮和ＩＬ－１０对肺泡巨噬细胞炎症反应的调节作用,方法：小鼠肺泡汇噬细胞（ＡＭ）受脂多糖（ＬＰＳ）１０ｍｇ．Ｌ＾－１刺激同时,加入一氧化氮合酶抑制剂Ｓ－硫酸甲基异硫脲（ＳＭＴ）或一氧化氮供体Ｓ－亚硝基乙酰青霉胺（ＳＮＡＰ）,ＥＬＩＳＡ法测定上清液中ＴＮＦα,ＩＬ－１β,ＩＬ－６和ＩＬ－１０浓度,结果：ＡＭ受ＬＰＳ刺激后,ＴＮＦα,ＩＬ－１β和ＩＬ－６释放峰值分别在６,１２和２４小时,     

Immunomodulating effects of methionine enkephalin

甲硫氨酸脑啡肽（ＭｅｔＥｎｋ）在神经免疫内分泌调节网络中的作用引起广泛关注．作者等实验证明它能使ＬＰＳ刺激的小鼠腹腔巨噬细胞产生ＩＬ１，纳洛酮不能阻止这种作用．ＭｅｔＥｎｋ促进小鼠脾淋巴细胞增殖和ＩＬ２、ＩＬ６的产生，这种上调作用与增强此二种白细胞介素ｍＲＮＡ转录并提高其稳定性有关．因此ＭｅｔＥｎｋ在增强前炎性细胞因子表达方面是一个重要的免疫调节信号分子．     

精氨酸对阻塞性黄疸大鼠 IL-1 及 IL-2 的影响

目的：观察精氨酸在病理状态下对免疫功能的调节作用；方法：建立大鼠阻塞性黄疸模型，采用胸腺细胞及ＣｏｎＡ激活的脾细胞增殖法检测阻塞性黄疸大鼠ＩＬ－１及ＩＬ－２的活性；结果：阻塞性黄疸大鼠ＬＰＳ诱导的腹腔巨噬细胞产生的ＩＬ－１及Ｔ细胞分泌的ＩＬ－２均降低，精氨酸（２．７ｇ·ｋｇ－１·ｄ－１×７ｄ，ｉｇ）能使上述改变恢复正常，且精氨酸在该剂量对正常及阻塞性黄疸大鼠的肝肾功能无明显影响；结论：精氨酸对阻塞性黄疸大鼠免疫功能的降低有上调作用。     

苦参碱对纤维蛋白纤维蛋白原降解产物诱导血管细胞损伤、增殖及腹腔巨噬细胞释放IL-1的影响

目的：研究苦参碱（Ｍａｔ）对纤维蛋白纤维蛋白原降解产物（ＦＦＤＰ）作用的影响。方法：大鼠主动脉内皮细胞损伤以乳酸脱氢酶释放测定;大鼠主动脉平滑肌细胞增殖采用结晶紫染色法测定;白细胞介素１活性采用小鼠胸腺细胞增殖法测定。结果：ＦＦＤＰ能促进大鼠主动脉内皮细胞释放乳酸脱氢酶,诱导大鼠主动脉平滑肌细胞增殖,并促使小鼠腹腔巨噬细胞分泌ＩＬ１增加。结论：Ｍａｔ可抑制ＦＦＤＰ的作用。对动脉粥样硬化的防治可能有一定意义。     

白芍总甙对B淋巴细胞增殖和白介素1生成的调节作用

白芍总甙（ＴＧＰ）对脂多糖（ＬＰＳ）诱导的小鼠脾淋巴细胞增殖反应的量效曲线呈钟形，用贴壁法除去脾细胞中巨噬细胞（ＭΦ）或加入１０μｍｏｌ·Ｌ１吲哚美辛（Ｉｎｄ）可使ＴＧＰ量效曲线的下降支消失，再加５％同系小鼠腹腔ＭΦ中或前列腺素Ｅ２（ＰＧＥ２）０．０２２０μｍｏｌ·Ｌ１可使量效曲线下降支再现．同步检测ＴＧＰ对ＬＰＳ诱导大鼠腹腔ＭΦ产生ＰＧＥ２与白介素１（ＩＬ１）．结果表明，ＴＧＰ０．５－３ｌ２．５μｇ·ｍＬ１对ＬＰＳ诱导的ＩＬ－１产生曲线呈钟形．而ＴＧＰＬＰＳ的ＰＧＥ２产生曲线呈浓度依赖性地增高；在１２．５－３１２．５μｇ·ｍＬＴＧＰ范围内，１０μｍｏｌ·Ｌ１Ｉｎｄ可使高浓度ＴＣＰＬＰＳ的ＩＬ－１释放曲线明显抬高。提示ＴＧＰ对ＬＰＳ诱导的Ｂ细胞增殖反应和ＩＬ－１诱生的负调节作用都与其促进ＭΦ释放ＰＧＥ２有关．     

西洋参多糖组份 1(PPQ-1)对小鼠脾淋巴细胞合成细胞因子的影响

目的：筛选高效、低毒的生物应答反应调节剂。方法：采用淋巴母细胞增殖法、胸腺细胞增殖法、骨髓干细胞增殖法及微量病变抑制法，分别检测了西洋参多糖组份１（ｐｏｌｙｓａｃｃｈａｒｉｄｅｆｒｏｍｐａｎａｘｑｕｉｎｑｕｅｆｏｌｉｕｍ，ＰＰＱ－１－①～④）体外对小鼠脾细胞合成细胞因子的影响。结果：ＰＰＱ－１－①～④虽然单独不能诱导小鼠脾细胞合成ＩＬ－２，但可协同亚适量ＣｏｎＡ（２．５ｍｇ·Ｌ－１）诱导合成ＩＬ－２，其含量为２５０～３００ｕ。另外，这四种多糖也可单独及协同亚适量ＣｏｎＡ（２．５ｍｇ·Ｌ－１）诱导合成ＩＬ－１及ＩＦＮ，ＰＰＱ－１－①～④单独还可明显诱导脾细胞合成ＩＬ－３样活性物质。结论：ＰＰＱ－１－①～④具有一定的免疫调节作用。     

The Role of Tumor Necrosis Factor and Interleukin 1 in the Immunoinflammatory Response

Monocytes and tissue macrophages produce at least two groups of protein mediators of inflammation, interleukin 1 (IL-1) and tumor necrosis factor (TNF). Recent studies have emphasized that TNF and IL-1 modulate the inflammatory function of endothelial cells, leukocytes, and fibroblasts. Although these cytokines share a number of biologic properties, they have quite distinct gene and protein structures. It is our purpose to focus on the role of these mediators in inflammation.     

酵母多糖对小鼠腹腔巨噬细胞产生一氧化氮和白细胞介素-1的影响

目的探讨酵母多糖对小鼠腹腔巨噬细胞产生一氧化氮 (NO)和白细胞介素 1(IL 1)的影响。方法将不同剂量的酵母多糖加入体外培养的小鼠腹腔巨噬细胞中 ,取细胞培养上清液根据Griess反应检测NO-2 的量 ,间接反映巨噬细胞产生NO的生成量 ,并用溴化四唑蓝 (MTT)比色法检测上清液中IL 1的生成量。结果酵母多糖可明显促进小鼠腹腔巨细胞产生NO和IL 1,NO的生成量呈现剂量依赖关系。结论酵母多糖可诱导小鼠腹腔巨噬细胞产生NO和IL 1,可能是酵母多糖调节机体免疫功能、杀伤病原微生物和抗肿瘤的重要途径     

Discrimination of skin sensitizers from non‐sensitizers by interleukin‐1α and interleukin‐6 production on cultured human keratinocytes

In vitro testing methods for classifying sensitizers could be valuable alternatives to in vivo sensitization testing using animal models, such as the murine local lymph node assay (LLNA) and the guinea pig maximization test (GMT), but there remains a need for in vitro methods that are more accurate and simpler to distinguish skin sensitizers from non‐sensitizers. Thus, the aim of our study was to establish an in vitro assay as a screening tool for detecting skin sensitizers using the human keratinocyte cell line, HaCaT. HaCaT cells were exposed to 16 relevant skin sensitizers and 6 skin non‐sensitizers. The highest dose used was the dose causing 75% cell viability (CV75) that we determined by an MTT [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide] assay. The levels of extracellular production of interleukin‐1α (IL‐1α) and IL‐6 were measured. The sensitivity of IL‐1α was 63%, specificity was 83% and accuracy was 68%. In the case of IL‐6, sensitivity: 69%, specificity: 83% and accuracy: 73%. Thus, this study suggests that measuring extracellular production of pro‐inflammatory cytokines IL‐1α and IL‐6 by human HaCaT cells may potentially classify skin sensitizers from non‐sensitizers. Copyright © 2015 John Wiley & Sons, Ltd.     

Interleukin-1β-induced, nitric oxide-dependent and -independent inhibition of vascular smooth muscle contraction

Stimulation of vascular smooth muscle by bacterial lipopolysaccharide has been shown to produce interleukin-1β and to induce vasodilation in septic shock. To understand the mechanisms of interleukin-1β-induced relaxation, we examined the effects of interleukin-1β on contractility and cyclic GMP contents of vascular smooth muscle. After treatment of the rat aorta with interleukin-1β (20 ng/ml) for 6 h, the cyclic GMP content increased and the contraction induced by phenylephrine (1 μM) was partially inhibited. An inhibitor of nitric oxide (NO) synthase, N^G-monomethyl-

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-arginine (

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-NMMA, 100 μM), prevented the inhibitory effect of interleukin-1β. After treatment with interleukin-1β for 24 h, the phenylephrine-induced contraction was inhibited more strongly. Neither

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-NMMA (100 μM) nor aminoguanidine (100 μM) reversed the inhibition, whereas methylene blue (10 μM) partially reversed the inhibition. After treatment with interleukin-1β for 12 or 24 h, the cyclic GMP content increased but to a level lower than that obtained with a 6-h treatment. The effects of sodium nitroprusside (1 μM) to inhibit the phenylephrine-induced contraction and to increase the cyclic GMP content were markedly suppressed by the 24-h interleukin-1β treatment. In contrast, the 24-h interleukin-1β treatment did not change the ability of 8-bromo-cGMP to relax the phenylephrine-stimulated aorta. Addition of

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-NMMA (1 mM) during the 24 h treatment prevented NO production and preserved the sodium nitroprusside-induced cGMP generation by interleukin-1β. The 24 h interleukin-1β treatment increased the threshold concentration of KCl needed to induce contraction without changing the maximum contraction. In the presence of 25.4 mM KCl or the non-selective K⁺ channel inhibitor, tetraethylammonium, the inhibitory effect of the 24-h interleukin-1β treatment on phenylephrine-induced contraction was restored. These results suggest that interleukin-1β inhibits vascular smooth muscle contraction by a time-dependent, dual mechanism. After a 6-h treatment with interleukin-1β, the NO/cyclic GMP system is activated. After a 24-h interleukin-1β treatment, in contrast, the NO/cyclic GMP system may be desensitized and the contraction of vascular smooth muscle is inhibited by another mechanism, possibly membrane hyperpolarization.     

Morphological alterations and elevations in tumor necrosis factor-alpha,interleukin (IL)-1alpha,and IL-6 in mixed glia cultures following exposure to trimethyltin: modulation by proinflammatory cytokine recombinant proteins and neutralizing antibodies

Trimethyltin (TMT), is a hippocampal neurotoxicant characterized by neuronal degeneration, astrogliosis, and microglia reactivity with an associated elevation in proinflammatory cytokine mRNA levels. To examine the role of proinflammatory cytokines in the TMT-induced glia response, mixed cortical glia cultures were exposed to TMT and morphological and cytokine responses were examined. Morphological changes in the glia monolayer, enlarged, rounded cell bodies and retraction of the monolayer into distinct GFAP+ dense processes, displayed a dose (1, 5, and 10 microM TMT) and temporal response (6-48 h), accompanied by clustering of OX-42+ microglia. Tumor necrosis factor-alpha (TNF), interleukin (IL)-1alpha, and IL-6 mRNA levels were elevated by 3 and 6 h of TMT (10 microM) and proteins by 24 h. Recombinant proteins for IL-1alpha (100 pg/ml) and IL-6 (10 ng/ml) exacerbated the morphological response to TMT while those for TNFalpha (150 pg/ml) did not. Neutralizing antibodies (1:100) to IL-1alpha and IL-6 showed a slight decrease in the severity of the morphological response to TMT while, at 24 h, TNFalpha antibodies (1:100) and an antibody cocktail offered a significant level of protection. At 6 h, the neutralizing antibodies to TNFalpha or IL-1alpha did not elevate basal cytokine mRNA levels, however, IL-6 and the cocktail of antibodies significantly elevated IL-1alpha, IL-1beta, and IL-6 mRNA levels. The specific elevation in IL-1alpha and IL-6 mRNA levels induced by TMT remained evident only in cells coexposed to anti-TNFalpha. Similar responses in cytokine mRNA levels were seen in cocultures of hippocampal neurons and glia exposed to TMT. These data suggest a relationship between microglia activation, proinflammatory cytokine release, and glia morphological responses, the significance of which remains to be determined, as well as, the impact on neuronal degeneration.     

白细胞介素1α对多形核白细胞凋亡的抑制作用

目的　研究白介素 1α(IL 1α)对多形核白细胞 (PMN)凋亡过程的影响。方法　采用凋亡的形态学和DNA琼脂电泳等方法测定 ,并在粘附式细胞仪上观察了PMN内游离钙浓度 ([Ca2 +]i)变化。结果　IL 1α具有抗PMN凋亡 ,延长其存活时间的作用 ,且能提高PMN的 [Ca2 +]i 浓度。结论　IL 1α具有抗PMN凋亡和提高 [Ca2 +]i 浓度的作用 ,提示钙离子在IL 1α抗PMN凋亡过程中作为第二信使 ,转导相应信号。     

hrHPV 在宫颈癌中的感染状况及对 Caspase-1 和 IL-1β 表达的影响及意义

摘要： 目的 探讨宫颈癌中高危人乳头瘤病毒（hrHPV）感染状况及对半胱氨酸天冬氨酸蛋白酶（Caspase） -1 和白细胞介素（IL） -1β表达的影响及临床意义。方法 以 102 例宫颈癌患者（宫颈癌组）、 60 例宫颈上皮内瘤样病变（CIN 组） 及宫颈正常的患者 30 例 （对照组） 为研究对象, PCR-反向点杂交法结合 DNA 芯片技术对各组 hrHPV DNA 进行感染和分型检测。免疫组化 SP 法检测各组 Caspase-1 和 IL-1β的表达。分析宫颈癌患者 hrHPV 感染者 （阳性组）和阴性组、 单一类型感染与多重感染中 2 指标的表达差异。考察 Caspase-1 和 IL-1β表达与宫颈癌患者临床病理参数的关系。结果 宫颈癌组 hrHPV 感染 （阳性组） 75 例 （73.5％）, 检出 hrHPV 11 种, 其中单一类型和多重 hrHPV 感染分别为 61 例（81.3％）和 14 例（18.7％）。宫颈癌组 hrHPV 感染率高于 CIN 组及对照组（36.7％和 6.7％）; Cas⁃ pase-1 和 IL-1β阳性表达率（61.8%和 51.0%）高于对照组（26.7%和 23.3%）, Caspase-1 阳性表达率高于 CIN 组（40.0%, 均 P＜0.01）。宫颈癌患者 hrHPV DNA 表达阴性组的 Caspase-1 和 IL-1β阳性表达率 （77.8%和 74.1%） 均高于相应阳性组 （56.0%和 42.7%）。Caspase-1 和 IL-1β在 hrHPV 单一感染组与多重感染组中阳性表达率差异均无统计学意义 （P＞0.05）。宫颈癌组的 Caspase-1 和 IL-1β蛋白的表达与癌细胞分级、 肿瘤大小、 淋巴结转移及临床分期有关 （P＜0.05 或 P＜0.01）。结论 宫颈癌中存在 hrHPV 单一和多重感染, 且感染率高; hrHPV 可抑制 Caspase-1 和 IL-1β的表达, 促进宫颈癌进展。