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81.
蛋白酶激活受体1介导人肺上皮细胞分泌白细胞介素-8 总被引:1,自引:0,他引:1
目的探讨蛋白酶激活受体1(PAR1)激动肽和凝血酶对人肺上皮细胞白细胞介索-8(IL-8)分泌的影响。方法人肺上皮细胞系A549细胞分别接种于12孔培养板各孔内,并分别用不同浓度的PAR1激动肽SFLLR和反PAR1激动肽RLLFS以及不同浓度的凝血酶和/或凝血酶抑制剂水蛭索进行刺激,刺激时间为2和16h。用ELISA方法检测上清液中的IL-8水平。结果经过16h的培养,SFLLR可引起浓度相关性IL-8的释放增加,增加到300μmol/L时诱导IL-8的释放量比基础分泌量增加了近16倍,RLLFS不能引起IL-8的释放增加。凝血酶也可引起浓度相关性IL-8释放.凝血酶在浓度1kU/L时就可引起IL-8释放量增加,10kU/L时诱导IL-8释放量达高峰,为基础分泌量的7.5倍。水蛭索可以抑制凝血酶对IL-8的释放作用。时间相关曲线表明,PAR1介导的IL-8释放从2h起即可引起增加,16h达高峰。结论PAR1激动肽和凝血酶可促进人肺上皮细胞分泌IL-8,PAR1拮抗剂和凝血酶抑制剂可能具有抗炎作用。 相似文献
82.
A rapid nonsterile short-term assay has been investigated in which percent inhibition of incorporation of the DNA precursor (3H)-thymidine is measured following exposure of tumor cells to the test drugs. To evaluate the usefulness of the short-term assay in providing a rapid reliable assessment of chemotherapeutic response, the short-term assay was compared with the soft agar clonogenic assay. Sensitivity to five anticancer drugs was compared using three human tumor cell lines (epidermoid carcinoma of the oral cavity, pancreatic carcinoma, and bladder carcinoma). The short-term assay produced results that were similar to results of the clonogenic assay in two of the three tumors tested, for three drugs (cis-platin, doxorubicin, and BCNU), but did not detect responses to two antimetabolites (5-FU and MTX) in any tumor. Further studies of this short-term assay should focus on alkylating agents and other nonantimetabolites. 相似文献
83.
本研究建立了大鼠气管上皮细胞体内-体外转化模型,大鼠气管内滴注苯并芘,三天后处死大鼠,消化气管上皮细胞,接种于无血清完全培养基。细胞形成集落后,换为选择培养基继续培养五周,统计转化率。结果显示,25mg/kg和50mg/kg的苯并芘可诱导大鼠气管上皮细胞转化及微核增加,用同样方法研究了煤焦沥青提取物,结果表明,剂量为8mg/kg和25mg/kg的煤焦沥青提取物能明显诱导大鼠气管上皮细胞转化。 相似文献
84.
G. Wu S. F. Fan Z.-H. Lu R. W. Ledeen S. M. Crain 《Journal of neuroscience research》1995,42(4):493-503
Prolongation of the action potential duration of dorsal root ganglion (DRG) neurons by low (nM) concentrations of opioids occurs through activation of excitatory opioid receptors that are positively coupled via Gs regulatory protein to adenylate cyclase. Previous results suggested GM1 ganglioside to have an essential role in regulating this excitatory response, but not the inhibitory (APD-shortening) response to higher (μM) opioid concentrations. Furthermore, it was proposed that synthesis of GM1 is upregulated by prolonged activation of excitatory opioid receptor functions. To explore this possibility we have utilized cultures of hybrid F11 cells to carry out closely correlated electrophysiological and biochemical analyses of the effects of chronic opioid treatment on a homogeneous population of clonal cells which express many functions characteristic of DRG neurons. We show that chronic opioid exposure of F11 cells does, in fact, result in elevated levels of GM1 as well as cyclic adenosine monophosphate (AMP), concomitant with the onset of opioid excitatory supersensitivity as manifested by naloxone-evoked decreases in voltage-dependent membrane K+ currents. Such elevation of GM1 would be expected to enhance the efficacy of excitatory opioid receptor activation of the Gs/adenylate cyclase/cyclic AMP system, thereby providing a positive feedback mechanism that may account for the remarkable supersensitivity of chronic opioid-treated neurons to the excitatory effects of opioid agonists as well as antagonists. These in vitro findings may provide novel insights into the mechanisms underlying naloxone-precipitated withdrawal syndromes and opioid-induced hyperalgesia after chronic opiatf addiction in vivo. © 1995 Wiley-Liss, Inc. 相似文献
85.
钙拮抗剂TMB-8抑制BHQ,NE和KCl引起的培养乳牛基底动脉单个平滑肌细胞内游离钙的升高 总被引:1,自引:0,他引:1
用AR CM MIC阳离子测定系统,测量单个细胞内游离钙浓度([Ca2+]i),研究8-(N,N-二乙胺)-n-辛基 3,4,5-三甲氧基苯甲酸酯(TMB-8)对培养乳牛基底动脉平滑肌[Ca2+]i的作用。在细胞外钙浓度为1.3mmol·L-1时,TMB-8(30μmol·L-1)可明显抑制BHQ,NE及KCl引起[Ca2+]i的升高。在细胞外钙为零+EGTA 0.1mmol·L-1时,TMB-8(10,30及100μmol·L-1)可浓度依赖性地降低静息[Ca2+]i,TMB-8(30μmol·L-1)可几乎完全阻断BHQ及NE引起[Ca2+]i的增加。研究表明TMB-8降低培养乳牛基底动脉平滑肌[Ca2+]i的机制,主要是抑制肌浆网Ca2+的释放,或增加肌浆网对Ca2+的摄入,并由此间接地抑制细胞外钙的内流。 相似文献
86.
M. E. Perry Y. Mustafa S. K. Wood M. I. D. Cawley D. C. Dumonde K. A. Brown 《Rheumatology international》1997,17(4):169-174
A morphological examination of synovial tissue from 25 patients with rheumatoid arthritis revealed that binucleated or multinucleated
plasma cells were present in all samples and absent in synovia obtained from 16 control patients. Plasma cells containing
two, three of four nuclei constitutet a mean 3% of the total plasma cell population. They were aways found amongst plasma
cell infiltrates and in close association with small blood vessels. Ultrastructural analysis found no evidence of cellular
membranes separating the individual nuclei in binucleated or multinucleated plasma cells, suggesting that the cells did not
arise from fusion. Some of these plasma cells had a diameter approaching 100 μm, and many were in intimate contact with macrophages.
The demonstration of a few cells with mitotic figures within the infiltrates suggests that the maintenance of plasma cell
numbers in rheumatoid synovium may depend, in part, upon their local proliferation.
Received: 25 August 1997 / Accepted: 2 October 1997 相似文献
87.
神经肽Y(NPY)是广泛分布于中枢神经系统和外周神经各部位的神经肽类物质。本实验观察NPY在体外对几种免疫细胞活性的直接作用。结果表明,NPY对小鼠T淋巴细胞丝裂原反应性和NK细胞的杀伤活性均无明显影响(P>0.05),对巨噬细胞分泌溶菌酶有明显抑制作用(P<0.05);而对B淋巴细胞丝裂原反应性则有明显的促进作用(P<0.05)。上述结果提示,NPY对部分免疫细胞功能的影响因细胞种类而异。 相似文献
88.
采集23名产妇的脐带血和8名正常成人的外周血制备LAK细胞,随机分为4组,在培养第3,5,7,14天,分别利用MTT法和^125I-UdR释放法对4组LAK细胞的增殖力和杀伤活性进行了测定,同时用细胞毒方法测定培养7天的LAK细胞的免疫表型。结果发现,在不同培养时间,脐血来源的LAK细胞增殖力显著高于成人血LAK细胞(P〈0.05或P〈0.01),成人血清组,脐血血清组,红细胞组LAK细胞增殖力有 相似文献
89.
PACAP is a hypothalamic hypophysiotropic factor that acts upon a number of pituitary cells, including gonadotrophs. In the gonadotroph-derived αT3-1 cell line, PACAP acts via PVR1 receptors to stimulate adenylyl cyclase and phosphoinositidase C. PACAP-stimulated cAMP accumulation is inhibited by protein kinase C-activating phorbol esters in these cells and the current work was undertaken primarily to establish whether it is also subject to homologous regulation. In acute experiments, PACAP27-stimulated cAMP accumulation (intracellular plus extracellular) was measured (in the presence of phosphodiesterase inhibitor) both in intact cells and in cell membranes. The peptide increased cAMP accumulation, but initial rates of PACAP27-stimulated cAMP accumulation were reduced to between 10 and 50% within 10 min of stimulation in both cells and membranes. The initial rate of forskolin-stimulated cAMP accumulation was maintained in membranes but not in intact cells (although the deviation from linearity was less pronounced than with PACAP27). Thus, rapid homologous desensitization to PACAP27 occurs in intact αT3-1 cells, but is not entirely receptor specific. Rapid homologous desensitization of PACAP27-stimulated cAMP accumulation also occurred in the presence of a protein kinase C activating phorbol ester, which inhibited cAMP accumulation without altering the kinetics of the PACAP27 effect. Brief pre-treatment (3 min) with PACAP27 also reduced the ability of PACAP27, but not gonadotrophin-releasing hormone, to cause a spike-type elevation of cytosolic Ca2+ concentration (a consequence of phosphoinositidase C activation). In chronic desensitization studies, pre-treatment for 6 h with PACAP27 caused a dose-dependent (IC50 approximately 10 nM) reduction of PACAP-stimulated cAMP accumulation and down regulated cell surface PVR1 receptors (to approximately 50%). Thus, it appears that PACAP27-stimulated (PVR-1 receptor mediated) adenylyl cyclase undergoes rapid homologous desensitization in αT3-1 cells, which is paralleled by homologous desensitization of PACAP27-stimulated phosphoinositidase C activity and involves mechanisms distinct from those underlying heterologous desensitization by phorbol esters. Chronic desensitization of PACAP-stimulated cAMP accumulation and down-regulation of cell surface PVR-1 receptors also occurs in these cells although the receptor loss may not entirely explain the observed desensitization. 相似文献
90.
Mice homozygous for the lpr mutation have B and T cell defects and develop autoantibodies, suggesting that lpr plays a role in their genesis. The lpr defect has been identified as a mutation in the apoptosis-associated Fas receptor (FasR) gene. To begin to define the role of FasR in B cells, we have surveyed FasR expression on B-lineage cells from early progenitors in the bone marrow through their maturation in the periphery. Contrary to some reports, we found that FasR is expressed on B cells at all stages of their development and is highest on germinal center B cells. FasR is not expressed on lpr/lpr-derived cells. These data are consistent with the idea that lpr/lpr mice have an intrinsic B cell defect that may be manifested in developing as well as peripheral B cells. An unexpected finding is that B-1 (CD5) B cells do not constitutively express FasR: FasR becomes detectable on B-1 B cells only after activation. 相似文献