人肺泡巨噬细胞条件培养上清对人胚肺纤维母细胞生长的调节效应

对人肺泡巨噬细胞(AM)对人胚肺纤维母细胞(FB)生长的调节效应进行研究,结果表明经SiO_2刺激后的AM上清能显著促进FB增殖,对照AM上清(无刺激物)作用次之,而经LPS刺激的AM上清作用最低。为检查上述活性与AM上清中IL-1含量是否平行,对这三种条件培养上清中的IL-1活性也分别作了检测。结果表明IL-1活性以LPS刺激上清为最高,而对照和SiO_2刺激上清其IL-1活性较低,提示AM上清中可能存在一些在不同激活条件下产生的IL-1以外的物质,在调节FB生长方面起重要的作用。     

IL-1促进大鼠肺纤维母细胞和小鼠胸腺细胞增殖的效应动力学比较

我们对IL-1促进纤维母细胞和胸腺细胞增殖的效应动力学进行了比较,结果表明:尽管IL-1能促进两种细胞的增殖,但在效应动力学模式上则完全不同。对于纤维母细胞,IL-1的最佳效应时间为休止态细胞进入细胞周期后的20～24h,而对于胸腺细胞,其最佳效应时间为休止态细胞进入细胞周期的初期。由此表明,IL-1对这两种细胞的效应可能存在着不同的细胞生物学和分子生物学机制。     

肺泡巨噬细胞因子与肺纤维母细胞

本文对有关肺泡巨噬细胞的分泌产物如生长因子、纤维粘连蛋白以及IL-1、TNF 等细胞因子作了简述,并对这些产物在正常和病理状态下对肺纤维母细胞生长的调节效应作了简要评介,认为在病理状态下肺泡巨噬细胞分泌产物的不平衡可能是导致肺纤维母细胞增生的主要原因。     

MTT法分析肺泡Mφ上清促纤维母细胞生长活性

本文对MTT比色法用于检测肺泡巨噬细胞上清对纤维母细胞的促生长活性的条件进行了探讨。结果表明:对于实验所选用的三种纤维母细胞,即NIH3T3细胞、人胚肺纤维母细胞、大鼠肺纤维母细胞,在细胞浓度为1×10~5-5×10~6/ml之间,和经低血清浓度(0.4％FCS)培养4—5天后,MTT比色法能较为敏感地反映出矽肺大鼠肺泡巨噬细胞上清对三种纤维母细胞的促生长效应。     

IL-11及其作用

近来Paul 等用来自骨髓的纤维母细胞分离出了与造血和免疫都有关的IL-11。1.IL-11的cDNA 克隆Paul 等采用灵长类纤维母细胞建立了能维持人类和灵长类多能干细胞生长的Pu-_(34)细胞株。如以IL-1α刺激之,则可产生具有刺激鼠浆细胞-T_(1165)增殖活性的新的IL。由此细胞株建立cDNA文库,转染给COD-1细胞,然后筛选,得到具有刺激活性的质粒pCIR6,它的cDNA由597个核苷酸构成,得到的蛋白质分子量为23KDa,另外从胎儿肺组织纤维母细胞     

IL-1和IL-1R拮抗剂在人类风湿性关节炎滑膜组织巨噬细胞中的表达

IL-1是介导类风湿性关节炎(RA)炎症和炎症破坏的重要因素,它能促进纤维母细胞分泌前列腺素(PGE_2)和胶原酶,并能提高这些细胞表面的粘附分子的表达.IL-1也能激活单核细胞和中性粒细胞并能促进纤维母细胞和内皮细胞生长.而最近已得到分离、纯化、克隆并且表达的IL-1受体拮     

人皮肤纤维母细胞高密度脂蛋白的受体的研究

本实验用正常人血清HDL_3与体外培养的正常人皮肤纤维母细胞进行了受体结合实验,并研究了HDL_3清除细胞内胆固醇(Ch)的作用。结果表明,人皮肤纤维母细胞上有不同于LDL受体的HDL受体。此受体不受钙离子及胰蛋白酶的影响;用Ch孵育细胞可使细胞结合~(125)I-HDL_3的量明显增加(P<0.05),而用无脂蛋白血清(LPDS)孵育细胞则可减少细胞结合~(125)I-HDL_3的量(P<0.05),这些说明HDL受体受细胞内Ch含量的调节。HDL_3清除细胞内Ch的浓度效应曲线与细胞特异性结合HDL_3的浓度效应曲线相似,均为可饱和图形;亚胺环已酮可使HDL_3清除细胞Ch的能力有所下降,提示人皮肤纤维母细胞上HDL受体与HDL_3清除细胞Ch的功能有关。     

白介素-1诱发的关节炎对关节内注射部位及频率的依赖性

IL-1在急性和慢性炎症中发挥重要作用。IL-1是T 细胞、B 细胞、纤维母细胞和软骨细胞的生长因子,IL-1可导致变性蛋白酶的合成和分泌,从而引起细胞间质的降解及软骨和骨的破坏。作者把人重组IL-1β关节内注入大鼠膝、踝关节实验,得出如下结论:(1)病变情况与注射部位有关。踝关节较膝关节需较小剂量就能引起炎症反应。机理不甚明了,可能与踝关节对IL-1更敏感及IL-1在     

人单核细胞趋化因子的分子特征及生物学效应

人单核细胞趋化因子是一种由76个氨基酸组成的单链肽,与中性粒细胞趋化因子IL-8有24％的分子同源性,产自于一些肿瘤细胞、T细胞、单核巨噬细胞、纤维母细胞和内皮细胞等,可调节单核细胞的再循环。因此,对免疫和炎症反应具有重要的调节效应。     

IL-10对人肾小球系膜细胞合成细胞外基质的调节

有研究报道，IL-10可以抑制体外培养的人皮肤纤维母细胞胶原基因及蛋白的表达，提示其在细胞外基质的降解或重塑过程中也发挥一定的作用。肾小球系膜细胞与纤维母细胞之间有许多相似的特性，但IL-10能否调节系膜细胞的基质代谢，目前尚未见报道。因此，本实验将利用体外培养的人系膜细胞，观察IL-10对其分泌细胞外基质的影响。     

Immunobiological effects of fumonisin B1 in experimental subchronic mycotoxicoses in rats.

Fumonisin B1 (FB1), the principal secondary metabolite produced by the fungus Fusarium verticillioides (Gibberella fujikuroi mating population A), is a potent toxin that can be found in fungus-contaminated corn and corn-based food products. We have investigated the immunobiological effects of subchronic dietary exposure to FB1 in male Wistar rats. Animals were fed with diets containing 0 (control) or 100 ppm of FB1 for 12 weeks. The total FB1 intake on day 90 was 810 mg/kg of body weight. Food consumption, body weight, and body weight gain on day 90 were reduced in animals exposed to FB1. Histopathologic changes consisted of histiocytic perivascular infiltrate and an increased number of Kupffer cells in the liver, necrosis and apoptosis of tubular epithelial cells in the kidney, and increased mitotic figures and lymphocytic infiltrate in the small intestine. Serum enzyme alkaline phosphatase was significantly elevated in rats fed FB1, while triglyceride levels decreased compared to controls. Treatment with FB1 in vivo or in vitro did not have a significant effect on mitogen-induced proliferation of spleen mononuclear cells. However, increased levels of interleukin-4 (IL-4) and decreased levels of IL-10 were released by these cells in culture compared to controls. FB1 in vivo or in vitro decreased the hydrogen peroxide (H(2)O(2)) released by peritoneal macrophages, while no changes in levels of superoxide anion produced by total peritoneal cells were detected. The results from the present work demonstrate that subchronic FB1 intake could affect the small intestine and alter the interleukin profile and some main functions of macrophages in antitumor activity.     

Immunobiological Effects of Fumonisin B1 in Experimental Subchronic Mycotoxicoses in Rats

Fumonisin B1 (FB1), the principal secondary metabolite produced by the fungus Fusarium verticillioides (Gibberella fujikuroi mating population A), is a potent toxin that can be found in fungus-contaminated corn and corn-based food products. We have investigated the immunobiological effects of subchronic dietary exposure to FB1 in male Wistar rats. Animals were fed with diets containing 0 (control) or 100 ppm of FB1 for 12 weeks. The total FB1 intake on day 90 was 810 mg/kg of body weight. Food consumption, body weight, and body weight gain on day 90 were reduced in animals exposed to FB1. Histopathologic changes consisted of histiocytic perivascular infiltrate and an increased number of Kupffer cells in the liver, necrosis and apoptosis of tubular epithelial cells in the kidney, and increased mitotic figures and lymphocytic infiltrate in the small intestine. Serum enzyme alkaline phosphatase was significantly elevated in rats fed FB1, while triglyceride levels decreased compared to controls. Treatment with FB1 in vivo or in vitro did not have a significant effect on mitogen-induced proliferation of spleen mononuclear cells. However, increased levels of interleukin-4 (IL-4) and decreased levels of IL-10 were released by these cells in culture compared to controls. FB1 in vivo or in vitro decreased the hydrogen peroxide (H₂O₂) released by peritoneal macrophages, while no changes in levels of superoxide anion produced by total peritoneal cells were detected. The results from the present work demonstrate that subchronic FB1 intake could affect the small intestine and alter the interleukin profile and some main functions of macrophages in antitumor activity.     

Reduction of serum Interleukin-1-like activity after treatment with dexamethasone

The ability of steroids to modulate the appearance of Interleukin-1(IL-1) in vivo was evaluated in a model of endotoxin shock. High levels of IL-1 were found in serum from A/J mice which were sensitized with P. acnes and challenged with bacterial lipopolysaccharide (LPS). The factor appeared in the serum 2-4 hours after LPS challenge and was dependent on the period of P. acnes sensitization and the dose of LPS. Treating the mice with dexamethasone prior to LPS challenge resulted in significantly lower thymocyte proliferative activity in the serum. Three experiments demonstrated that this reduced activity reflects a decrease in IL-1. 1) The reduced activity was not due to the presence of proliferation inhibitors since mixing the serum from dexamethasone-treated mice with purified IL-1 or adding the equivalent amount of steroid directly to thymocyte cultures did not reduce the degree of proliferation. 2) When the serum was fractionated by gel filtration, the proliferative activity for both control and steroid treated sera eluted at 10-16 kilodaltons; however, the activity was nearly 50% less in the sample from steroid-treated mice. 3) In addition to thymocyte proliferative activity, IL-1 induces an increase in the serum titer of the acute phase protein known as serum amyloid A. Both serum- and gel-purified samples were able to induce the SAA, but again the samples from steroid-treated mice were much less active. We conclude that the factor produced in vivo has the properties of IL-1 and that the serum titre of the factor is reduced by dexamethasone treatment.     

Central role of IL-6 and MMP-1 for cross talk between human intestinal mast cells and human intestinal fibroblasts

Mast cells (MC) are key effector cells in allergic reactions but also involved in host defence, tissue remodeling, angiogenesis, and fibrogenesis. Here, we show that human intestinal fibroblasts (FB) suppress apoptosis in human intestinal MC dependent on IL-6. Intestinal FB produced IL-6 upon direct stimulation by intestinal MC in co-culture or by MC mediators such as TNF-α, IL-1β, tryptase or histamine. MC incubated with IL-6 survived for up to 3 weeks similar to MC co-cultured with FB and MC survival could be blocked by neutralizing anti-IL-6 Abs. Moreover, FB stimulated by MC mediators upregulated their expression of matrix metalloproteinase-1 (MMP-1), a key fibrolytic enzyme. Noteworthy, FB co-cultured with MC or treated with MMP-1 lost confluence and showed increased numbers of apoptotic cells. Our data indicate an intimate cross talk between mucosal MC and FB resulting in MC survival and induction of a fibrolytic rather than a profibrotic state in FB.     

金乌骨通胶囊对成骨细胞分泌白细胞介素1，6的影响

背景：课题组以往研究发现,金乌骨通胶囊对绝经后骨质疏松症具有明显的治疗作用,但其具体的机制尚不十分清楚。 目的：观察金乌骨通胶囊含药血清对成骨细胞分泌白细胞介素1,6的影响。 方法：切除雌性SD大鼠双侧卵巢制备去卵巢血清,灌胃给予去卵巢大鼠金乌骨通胶囊制备去卵巢含药血清。取第3代生长状况良好的出生24 h内SD大鼠的成骨细胞,分别加入正常雌性SD大鼠血清、去卵巢血清和去卵巢含药血清培养72 h。 结果与结论：酶联免疫吸附法检测显示,与正常血清组比较,去卵巢血清组成骨细胞白细胞介素1、白细胞介素6的表达明显升高(P < 0.01);与去卵巢血清组比较,去卵巢含药血清组白细胞介素1和白细胞介素6的表达明显降低(P < 0.05),与正常血清组比较,则无明显差异。提示金乌骨通胶囊可能通过抑制成骨细胞骨白细胞介素1和白细胞介素6的表达来实现治防治骨质疏松症的目的。     

In vivo biologic and immunohistochemical analysis of interleukin-1 alpha, beta and tumor necrosis factor during experimental endotoxemia. Kinetics, Kupffer cell expression, and glucocorticoid effects.

Using a model of sepsis induced by parenteral challenge of mice with bacterial lipopolysaccharide (LPS), the authors analyzed the in vivo expression of interleukin-1 (IL-1) alpha,beta and tumor necrosis factor (TNF). Both TNF and IL-1 alpha,beta were detected in hepatic sinusoidal macrophages (Kupffer cells), immunohistochemically. Kinetic analysis showed a clear sequence of synthesis. Tumor necrosis factor was produced first, reaching maximal expression at 1 hour after LPS challenge, then rapidly disappeared. IL-1 beta followed, reaching maximal expression at 2 to 3 hours, then dropped off by 6 hours. Interleukin-1 alpha expression reached a peak at 6 hours and had disappeared by 18 hours. Analysis of serum bioactivity also revealed sequential expression that correlated with immunohistochemical findings. Tumor necrosis factor was maximal at 1 hour and IL-1 at 6 hours. The IL-1 bioactivity was not due to interleukin-6 (IL-6), as this was depleted from specimens by immunoabsorption. Also IL-6 bioactivity reached maximal levels at 3 hours, earlier than IL-1. Pretreatment with 4 mg/kg dexamethasone significantly decreased Kupffer cell expression of TNF and IL-1 alpha (about 80% and 60% suppression, respectively) but had less effect on IL-1 beta expression (about 30% suppression). Accordingly, serum levels of TNF were suppressed by 75% while serum IL-1 was decreased by 39%, indicating differential sensitivity of these cytokines to glucocorticoids. Endogenous corticosteroid levels increased as TNF levels decreased, supporting the contention that glucocorticoids regulate TNF synthesis. In contrast, IL-1 levels rose concurrently with corticosterone. These data indicate a sequential activation of cytokine gene expression in vivo, which may be critical to the cascade of events leading to septic shock, and provide evidence that Kupffer cells are a major source of cytokines in endotoxemia. Finally, the differential sensitivity of cytokine expression to glucocorticoids may in part explain the inadequacy of the latter in the treatment of sepsis.     

The interconnection between cytokines and the factors of bactericidal action of neutrophiles in patients operated on under the conditions of cardiopulmonary bypass

The use of cardiopulmonary bypass (CPB) is associated with the development of a system inflammatory response. The subjects of the study were 48 patients with coronary heart disease (CHD), operated on under the condition of CPB. The following parameters were measured: the content of cation proteins and active oxygen forms in neutrophiles, the digesting capacity of these cells, and the serum levels of interleukins (IL)-1beta, 1ra, -4, -6, -8, and tumor necrosis factor-alpha (TNF-alpha). The measurements were made before performing coronary bypass surgery, and also 6 and 24 hours after surgery. The results showed that the levels of cytokines and the bactericidal activity of neutrophiles were elevated in CHD patients before surgery. The changes after surgery included an increased macrophageal digesting capacity with switching to oxygen-independent mechanisms, as well as increased levels of TNF-alpha, IL-1ra, and IL-1ra:IL-1beta. The changes were more prominent 6 hours after surgery. Oxygen-dependent killing was controlled mostly by IL-6 during the pre-operative period, and by this plus TNF-alpha 24 hours after surgery. The content of cation proteins in neutrophiles before surgery correlated with the concentrations of TNF-alpha and IL-8. These interconnections weakened 6 hours after surgery and became stronger 24 hours after it.     

Interleukin-3 plus interleukin-6 may improve chromosomal analysis of multiple myeloma: Cytologic and cytogenetic evidence in thirty-four patients

To better define the role of interleukin-3 (IL-3) and IL-6 in the cytogenetic analysis of multiple myeloma (MM), we performed concomitant chromosome and cytologic studies in 34 patients. In each case, 10–30 × 10⁶ bone marrow cells were incubated in two independent cultures consisting of conventional cytogenetic medium with and without IL-3 plus IL-6 added for 72 hours. 1-ml aliquots of each culture were aspirated at 24, 48, and 72 hours and exposed to colcemid for 6 hours. Cytospin preparations were then made and mitotic cells were counted and identified as plasma cells or as nonmalinant cells based on their reactivity with an appropriate anti κ/λ serum. Slides for conventional cytogenetic analysis were prepared at 72 hours. A greater than two-fold increase of mitotic plasma cells was observed in cytospin preparations from stimulated cultures versus unstimulated cultures in 15 of 34 cases, whereas a less than 2-fold increase, no variation or no mitosis was recorded in 19 cases. Comparison of the number of mitotic plasma cells in stimulated cultures at 24, 48, and 72 hours showed a decreased mitotic activity at 72 hours. Clonal abnormalities were detected by conventional cytogenetic analysis in 19 of 34 cases (55.8%). Recurrent clonal aberrations involved chromosome 13 (4 cases), chromosomes 1p, and 14q (3 cases); chromosomes 3p, 6q, 7q, and 9q (2 cases). We conclude that IL-3 + IL-6 may increase the number of dividing plasma cells in cytogenetic cultures and that a 2-day culture with these cytokines may facilitate the detection of chromosome abnormalities in MM.     

大鼠脑缺血再灌注损伤IL-8变化的研究

目的：探讨白细胞介素0－8（interleukin-8,IL-8)在脑缺血再灌注损伤中的变化。方法：采用改良Zea Longa线栓法大鼠大脑中动脉闭塞（middle cerebral artery occlusion,MCAO)模型,将大脑中动脉（MCA）先行闭塞2小时,然后进行再灌注不同的时间,应用双抗体夹心间接ELISA法检测实验组和对照组大鼠脑组织及血清中IL－8浓度,结果：缺血2小时再灌注1小时脑组织IL－8含量较低（P＜0．05）,随再灌注时间延长逐渐升高,至22小时达高峰,随后又降低;血清中IL－8含量于再灌注1小时是高,随后缓慢下降,再灌注46小时降至对照组水平;空白组,假手术组脑组织内IL－8含量高于缺血再灌注组（P＜0．01）,结论：IL－8具有双重作用,既参与脑组织的正常代谢及生理功能,又参与了脑缺血再灌注损伤的病理生理过程。