• 【人A1是一种Bcl-2-related基因,通过细胞因子和分化因子在白血病细胞中诱导。】 复制标题 收藏 收藏
    DOI:10.1038/sj.leu.2400719 复制DOI
    作者列表:Moreb JS,Schweder M
    BACKGROUND & AIMS: :Based on previously published observations regarding the protective effects of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) against gamma radiation, alkylating agents and ultraviolet radiation, we hypothesized that the protection against such DNA damaging treatments can be the result of a 'stress'-like response induced by these cytokines and mediated by early response cellular gene(s). By applying the mRNA differential display to RNA obtained from A549 lung carcinoma cell line that was incubated with 50 ng/ml IL-1 for 0, 1, 2, and 6 h, we identified several cDNA fragments that correspond to genes regulated by IL-1. The full length cDNA for one fragment was obtained using 5'RACE, cloned, sequenced, and found to be homologous to human A1, a Bcl-2-related gene. In this study, we report that the expression of human A1 is either absent or present at low levels in leukemic cells, while it is expressed in human bone marrow cells and abundant in peripheral blood progenitors. It is induced by IL-1 and TNF alpha in A549 lung carcinoma, bone marrow, and certain leukemic cells. A1 is also induced in leukemic cells during granulocytic or macrophage but not erythroid differentiation. In conclusion, this is the first demonstration that A1 is inducible by cytokines in human bone marrow and certain tumor cells as well as myeloid differentiation in leukemic cells.
    背景与目标: : 根据先前发表的关于interleukin-1 (IL-1) 和肿瘤坏死因子 α (TNF α) 对 γ 辐射,烷化剂和紫外线辐射的保护作用的观察结果,我们假设,针对此类DNA损伤治疗的保护可能是由这些细胞因子诱导并由早期反应细胞基因介导的 “压力” 样反应的结果。通过将mRNA差异显示应用于从A549肺癌细胞系获得的RNA,该细胞系与50 ng/ml IL-1孵育0、1、2和6小时,我们鉴定了几个与IL-1调控基因相对应的cDNA片段。使用5' 种族获得一个片段的全长cDNA,克隆,测序,并发现与Bcl-2-related基因人A1同源。在这项研究中,我们报告了人A1的表达在白血病细胞中不存在或低水平存在,而在人骨髓细胞中表达并在外周血祖细胞中表达丰富。在A549肺癌,骨髓和某些白血病细胞中,由IL-1和TNF α 诱导。在粒细胞或巨噬细胞期间,白血病细胞中也会诱导A1,但不会诱导红系分化。总之,这是A1被人骨髓和某些肿瘤细胞中的细胞因子以及白血病细胞中的髓样分化诱导的第一个证明。
  • 【2型糖尿病伴或不伴视网膜病变患者27种房水细胞因子的研究。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Dong N,Xu B,Wang B,Chu L
    BACKGROUND & AIMS: PURPOSE:To compare the changes in the levels of 27 aqueous humor cytokines between nondiabetic controls and patients with type 2 diabetes and to ascertain the association of these cytokines with diabetic retinopathy (DR). METHODS:Undiluted aqueous humor samples were obtained from 102 nondiabetic patients (102 eyes) and 136 consecutive diabetic patients (136 eyes) who were divided into nine groups according to the Early Treatment of Diabetic Retinopathy Study severity scale. The concentrations of 27 cytokines in the aqueous humor samples were measured using a multiplex bead immunoassay. RESULTS:Compared with the nondiabetic controls, the diabetic patients had significantly higher concentrations of interleukin-1β (IL-1β; p<0.001), IL-6 (p<0.001), IL-8 (p<0.001), monocyte chemoattractant protein-1 (p<0.001), interferon gamma-induced protein-10 (p<0.001), and vascular endothelial growth factor (p<0.001) in the aqueous humor. However, the IL-10 (p=0.002) and IL-12 (p=0.013) concentrations were significantly lower for the diabetic patients. There were no significant differences in the concentrations of other cytokines between the diabetic patients and the controls. The IL-1β, IL-6, IL-8, monocyte chemoattractant protein-1, and interferon gamma-induced protein-10 levels in the aqueous humor increased as the severity of DR increased. The correlation was significant. However, the vascular endothelial growth factor concentration was not correlated with the severity of DR. In addition, the IL-10 and IL-12 levels in the aqueous humor decreased as the severity of DR increased, and this negative correlation was significant. CONCLUSIONS:Various cytokines associated with inflammation and angiogenesis may contribute to the pathogenesis of DR, and chemokines may be more closely related to the development of this disease.
    背景与目标:
  • 【含有表皮葡萄球菌的凋亡中性粒细胞刺激巨噬细胞释放促炎细胞因子肿瘤坏死因子 α 和interleukin-6。】 复制标题 收藏 收藏
    DOI:10.1111/j.1574-695X.2008.00412.x 复制DOI
    作者列表:Wilsson A,Lind S,Ohman L,Nilsdotter-Augustinsson A,Lundqvist-Setterud H
    BACKGROUND & AIMS: :Staphylococcus epidermidis infections are usually nosocomial and involve colonization of biomaterials. The immune defense system cannot efficiently control the bacteria during these infections, which often results in protracted chronic inflammation, in which a key event is disturbed removal of neutrophils by tissue macrophages. While ingesting uninfected apoptotic neutrophils, macrophages release anti-inflammatory cytokines that lead to resolution of inflammation. In clinical studies, we have previously found elevated levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 in synovial fluid from prostheses infected with coagulase negative staphylococci. We show that macrophages phagocytosing apoptotic neutrophils containing S. epidermidis released TNF-alpha and interleukin-6, whereas macrophages phagocytosing spontaneously apoptotic neutrophils did not. This difference was not due to dissimilar phagocytic capacities, because macrophages ingested both types of neutrophils to the same extent. The activation was induced mainly by the apoptotic neutrophils themselves, not by the few remaining extracellular bacteria. Macrophages were not activated by apoptotic neutrophils that contained paraformaldehyde-killed S. epidermidis. Proinflammatory reactions induced by clearance of apoptotic neutrophils containing S. epidermidis might represent an important mechanism to combat the infective agent. This activation of macrophages may contribute to the development of chronic inflammation instead of inflammation resolution.
    背景与目标: : 表皮葡萄球菌感染通常是医院内的,涉及生物材料的定植。在这些感染期间,免疫防御系统无法有效控制细菌,这通常会导致长期的慢性炎症,其中关键事件是组织巨噬细胞干扰中性粒细胞的去除。在摄取未感染的凋亡中性粒细胞时,巨噬细胞会释放抗炎细胞因子,从而缓解炎症。在临床研究中,我们先前已发现感染凝固酶阴性葡萄球菌的假体的滑液中促炎细胞因子肿瘤坏死因子-α (TNF-α) 和interleukin-6水平升高。我们显示巨噬细胞吞噬含有表皮葡萄球菌的凋亡中性粒细胞释放TNF-α 和interleukin-6,而吞噬自发凋亡中性粒细胞的巨噬细胞却没有。这种差异不是由于吞噬能力不同,因为巨噬细胞在相同程度上摄取了两种类型的中性粒细胞。激活主要是由凋亡的中性粒细胞本身诱导的,而不是由少数剩余的细胞外细菌诱导的。巨噬细胞不被含有多聚甲醛杀死的表皮葡萄球菌的凋亡中性粒细胞激活。清除含有表皮葡萄球菌的凋亡中性粒细胞引起的促炎反应可能是对抗感染剂的重要机制。巨噬细胞的这种激活可能有助于慢性炎症的发展,而不是炎症的解决。
  • 【细胞因子基因白细胞介素家族的变异影响HIV-1合并感染的非裔美国青少年高危型HPV的清除。】 复制标题 收藏 收藏
    DOI:10.1016/j.humimm.2013.08.010 复制DOI
    作者列表:Sudenga SL,Wiener HW,Shendre A,Wilson CM,Tang J,Shrestha S
    BACKGROUND & AIMS: :Our work aimed to examine the potential influence of variants in interleukin/interleukin receptors genes on high-risk (HR-HPV) HPV clearance. Clearance of genital HR-HPV infection was evaluated for 134 HIV-1 seropositive African-American female adolescents from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort. Genotyping targeted 225 single nucleotide polymorphisms (SNPs) within the exons, 5' untranslated region (UTR) and 3' UTR sequences of 27 immune-related candidate genes encoding interleukin family of cytokines. Cox proportional hazard models were used to determine the association of type-specific HPV clearance adjusting for time-varying CD4+ T-cell count and low-risk (LR-HPV) HPV co-infections. HR-HPV clearance rates were significantly (p < 0.001) associated with five SNPs (rs228942, rs419598, rs315950, rs7737000, and rs9292618) mapped to coding and regulatory regions in three genes (IL2RB, IL1RN, and IL7R). These data suggest that the analyzed genetic variants in interleukin family of cytokines modulate HR-HPV clearance in HIV-1 seropositive African-Americans that warrants replication.
    背景与目标: : 我们的工作旨在研究白介素/白介素受体基因的变体对高危 (hr-hpv) HPV清除的潜在影响。从青少年护理和健康卓越 (REACH) 队列中评估了134名HIV-1血清阳性的非洲裔美国女性青少年的生殖器hr-hpv感染清除情况。基因分型针对编码细胞因子白介素家族的27个免疫相关候选基因的外显子内的225单核苷酸多态性 (snp) 、5' 非翻译区 (UTR) 和3'utr序列。Cox比例风险模型用于确定类型特异性HPV清除率与随时间变化的CD4 T细胞计数和低风险 (lr-hpv) HPV合并感染之间的关联。Hr-hpv清除率与五个snp (rs228942、rs419598、rs315950、rs7737000和rs9292618) 显著相关 (p <0.001),它们被定位到三个基因 (IL2RB、IL1RN和IL7R) 的编码和调控区。这些数据表明,所分析的细胞因子白细胞介素家族的遗传变异调节了HIV-1血清阳性的非洲裔美国人的hr-hpv清除率,这需要复制。
  • 【用睾丸生殖细胞免疫的小鼠脾细胞因子。】 复制标题 收藏 收藏
    DOI:10.1111/j.1365-2605.2007.00790.x 复制DOI
    作者列表:Tokunaga Y,Terayama H,Naito M,Qu N,Hirai S,Ogawa Y,Yi SQ,Itoh M
    BACKGROUND & AIMS: :We previously established that two subcutaneous injections of viable syngeneic testicular germ cells (TGC) alone can induce CD4+ T cell-dependent experimental autoimmune orchitis (EAO) in mice. This model is histologically characterized by lymphocytic infiltration into the testes and the following aspermatogenesis. In the present study, we investigated the dynamics of splenic cytokines in EAO, using specific enzyme-linked immunosorbent assay. We found that splenic production of both type 1 helper T cell (Th1) and type 2 helper T cell (Th2)-related cytokines increased after the second but not the first immunization with TGC, indicating that secondary immune responses are critical to the EAO induction. However, the production of Th1-related cytokines became predominant at the clinical stage of EAO. Additionally, serum FSH and inhibin-B increased and decreased, respectively, during EAO. On the other hand, LH did not significantly change and testosterone temporally increased during the same period. These results indicate that both Th1- and Th2-related cytokines are involved at the pre-clinical phase of EAO, but that Th1- rather than Th2-related cytokines are responsible for the clinical phase when spermatogenesis is disrupted but the Leydig cell function is well preserved.
    背景与目标: : 我们先前已经确定,仅皮下注射两次可行的同系睾丸生殖细胞 (TGC) 可以在小鼠中诱导CD4 T细胞依赖性实验性自身免疫性睾丸炎 (EAO)。该模型在组织学上的特征是淋巴细胞浸润到睾丸中,并发生以下的aspermatogenesis。在本研究中,我们使用特定的酶联免疫吸附测定法研究了EAO中脾细胞因子的动力学。我们发现,在第二次但第一次用TGC免疫后,1型辅助T细胞 (Th1) 和2型辅助T细胞 (Th2) 相关细胞因子的脾脏产生增加,这表明继发性免疫反应对EAO诱导至关重要。然而,在EAO的临床阶段,Th1-related细胞因子的产生成为主要。此外,在EAO期间,血清FSH和抑制素B分别升高和降低。另一方面,在同一时期,LH没有显着变化,睾丸激素暂时增加。这些结果表明,Th1-和Th2-related细胞因子都参与了EAO的临床前阶段,但是当精子发生被破坏但Leydig细胞功能得以很好地保留时,Th1-而不是Th2-related细胞因子负责临床阶段。
  • 【呼吸道合胞病毒与Th2细胞因子协同诱导最佳水平的TARC/ccl17。】 复制标题 收藏 收藏
    DOI:10.4049/jimmunol.179.3.1648 复制DOI
    作者列表:Monick MM,Powers LS,Hassan I,Groskreutz D,Yarovinsky TO,Barrett CW,Castilow EM,Tifrea D,Varga SM,Hunninghake GW
    BACKGROUND & AIMS: :Respiratory syncytial virus (RSV) is a ubiquitous virus that preferentially infects airway epithelial cells, causing asthma exacerbations and severe disease in immunocompromised hosts. Acute RSV infection induces inflammation in the lung. Thymus- and activation-regulated chemokine (TARC) recruits Th2 cells to sites of inflammation. We found that acute RSV infection of BALB/c mice increased TARC production in the lung. Immunization of BALB/c mice with individual RSV proteins can lead to the development of Th1- or Th2-biased T cell responses in the lung after RSV infection. We primed animals with a recombinant vaccinia virus expressing either the RSV fusion (F) protein or the RSV attachment (G) protein, inducing Th1- and Th2-biased pulmonary memory T cell responses, respectively. After RSV infection, TARC production significantly increased in the vaccinia virus G-primed animals only. These data suggest a positive feedback loop for TARC production between RSV infection and Th2 cytokines. RSV-infected lung epithelial cells cultured with IL-4 or IL-13 demonstrated a marked increase in the production of TARC. The synergistic effect of RSV and IL-4/IL-13 on TARC production reflected differential induction of NF kappa B and STAT6 by the two stimuli (both are in the TARC promoter). These findings demonstrate that RSV induces a chemokine TARC that has the potential to recruit Th2 cells to the lung.
    背景与目标: 呼吸道合胞病毒 (RSV) 是一种普遍存在的病毒,优先感染气道上皮细胞,在免疫功能低下的宿主中引起哮喘加重和严重疾病。急性RSV感染会引起肺部炎症。胸腺和激活调节的趋化因子 (TARC) 将Th2细胞募集到炎症部位。我们发现BALB/c小鼠的急性RSV感染增加了肺部的TARC产生。用单个RSV蛋白预防接种BALB/c小鼠可导致RSV感染后肺中Th1或Th2-biased T细胞反应的发展。我们用表达RSV融合 (F) 蛋白或RSV附着 (G) 蛋白的重组痘苗病毒引发动物,分别诱导Th1-和Th2-biased肺记忆T细胞反应。RSV感染后,仅在牛痘病毒G引发的动物中,TARC的产生显着增加。这些数据表明,RSV感染和Th2细胞因子之间的TARC产生存在正反馈环。用IL-4或IL-13培养的RSV感染的肺上皮细胞显示出TARC产生的显着增加。RSV和IL-4/IL-13对TARC产生的协同作用反映了两种刺激 (都在TARC启动子中) 对NF κ B和STAT6的不同诱导。这些发现表明RSV诱导趋化因子TARC,该趋化因子具有将Th2细胞募集到肺的潜力。
  • 【使用Luminex xMAP技术可以检测到脂多糖诱导的离散小鼠脑区域中细胞因子的增加。】 复制标题 收藏 收藏
    DOI:10.1016/j.jneumeth.2008.08.007 复制DOI
    作者列表:Datta SC,Opp MR
    BACKGROUND & AIMS: :Methods to determine cytokine protein content in samples of interest, such as enzyme-linked immunosorbent assay (ELISA), are often labor-intensive and costly. Furthermore, because ELISA requires relatively large sample volumes and protein concentrations, it is difficult using this technique to determine protein content for multiple cytokines from individual samples. Recently, Luminex has developed an open source hardware platform combining flow cytometry- and bead-based antibody capture that is capable of detecting multiple analytes from a single sample. In the present study we employed the Luminex 200 platform to determine the cytokine protein content in discrete brain regions of C57BL/6J mice. In spike-and-recovery experiments, known concentrations of murine recombinant interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)alpha were added either singly or as a mixture of all three to whole brain homogenates containing known quantities of total protein. Spiked samples were assayed for either a single cytokine or for multiple cytokines using 1-plex or 3-plex assay kits, respectively. In whole mouse brain homogenate we recovered between 81% and 103% of the recombinant cytokines. We then injected C57BL/6J mice intraperitoneally with bacterial lipopolysaccharide (LPS) and sacrificed them 4h later. We detected in samples taken from LPS-stimulated mice 4- to 870-fold increases in serum or spleen cytokine protein, and 1.5- to 16-fold increases in cytokine protein in discrete brain regions, relative to protein content in samples obtained from vehicle-treated animals. These results indicate that multiple cytokines may be reliably assayed from discrete regions of mouse brain using a single sample.
    背景与目标: : 确定目标样品中细胞因子蛋白含量的方法,例如酶联免疫吸附测定 (ELISA),通常是劳动密集型且昂贵的。此外,由于ELISA需要相对较大的样品体积和蛋白质浓度,因此使用该技术很难确定来自单个样品的多种细胞因子的蛋白质含量。最近,Luminex开发了一种结合流式细胞术和基于珠子的抗体捕获的开源硬件平台,该平台能够从单个样品中检测多种分析物。在本研究中,我们使用Luminex 200平台来确定C57BL/6J小鼠离散脑区域中的细胞因子蛋白含量。在穗和恢复实验中,已知浓度的鼠重组白细胞介素 (IL)-1β,IL-6,并且将肿瘤坏死因子 (TNF) α 单独或作为所有三种混合物添加到包含已知量的总蛋白的全脑匀浆中。使用1-plex或3-plex检测试剂盒对加标样品进行单一细胞因子或多种细胞因子的测定,分别。在整个小鼠脑匀浆中,我们回收了81% 至103% 的重组细胞因子。然后,我们向C57BL/6J小鼠腹腔注射细菌脂多糖 (LPS),并在4小时后将其处死。我们在从LPS刺激的小鼠身上采集的样本中检测到血清或脾脏增加4至870倍细胞因子蛋白,相对于从媒介物处理的动物获得的样品中的蛋白质含量,离散脑区域中的细胞因子蛋白增加1.5至16倍这些结果表明,使用单个样品可以从小鼠脑的离散区域可靠地测定多种细胞因子。
  • 【香烟烟雾冷凝物上调人成纤维细胞样滑膜细胞系中促炎细胞因子的基因和蛋白表达。】 复制标题 收藏 收藏
    DOI:10.1089/jir.2007.0081 复制DOI
    作者列表:Shizu M,Itoh Y,Sunahara R,Chujo S,Hayashi H,Ide Y,Takii T,Koshiko M,Chung SW,Hayakawa K,Miyazawa K,Hirose K,Onozaki K
    BACKGROUND & AIMS: :Rheumatoid arthritis (RA) is characterized by proliferation of synoviocytes that produce proinflammatory cytokines, which are implicated in the pathogenesis of RA. When human fibroblast-like synoviocytes line MH7A was treated with cigarette smoke condensate (CSC), either mainstream or sidestream, expression levels of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-8, and CYP1A1 mRNA were upregulated in both time- and dose-dependent manners. The upregulatory effects of CSC on these cytokines were not significantly inhibited by alpha-naphthoflavone, an aryl hydrocarbon receptor (AhR) antagonist, suggesting that the effects of CSC were independent of AhR. Cycloheximide treatment indicated that the augmenting effect of CSC on IL-1alpha, IL-1beta and IL-8, but not IL-6 and CYP1A1, mRNA expression requires de novo protein synthesis. CSC also induced cytokines at protein levels and further augmented the effects of tumor necrosis factor alpha on induction of these cytokines at both mRNA and protein levels. These results support the epidemiological studies indicating a strong association between heavy cigarette smoking and pathogenesis of RA.
    背景与目标: : 类风湿关节炎 (RA) 的特征是滑膜细胞的增殖,产生促炎细胞因子,这与RA的发病机理有关。当人类成纤维细胞样滑膜细胞系MH7A用香烟烟雾冷凝物 (CSC) 处理时,无论是主流还是侧流,白介素 (IL)-1α,IL-1beta,IL-6,IL-8和cyp1a1mrna的表达水平均随时间和剂量而增加。芳基烃受体 (AhR) 拮抗剂 α-萘黄酮并未显着抑制CSC对这些细胞因子的上调作用,这表明CSC的作用与AhR无关。环己酰亚胺处理表明,CSC对IL-1alpha,IL-1beta和IL-8的增强作用,但对IL-6和CYP1A1,mRNA表达不需要从头合成蛋白质。CSC还在蛋白质水平上诱导了细胞因子,并进一步增强了肿瘤坏死因子 α 在mRNA和蛋白质水平上诱导这些细胞因子的作用。这些结果支持流行病学研究,表明大量吸烟与RA的发病机理之间存在很强的关联。
  • 【细胞因子在哮喘中的作用的新见解。】 复制标题 收藏 收藏
    DOI:10.1136/jcp.54.8.577 复制DOI
    作者列表:Renauld JC
    BACKGROUND & AIMS: :Asthma is a triad of intermittent airway obstruction, bronchial smooth muscle cell hyperreactivity to bronchoconstrictors, and chronic bronchial inflammation. From an aetiological standpoint, asthma is a heterogeneous disease, but often appears as a form of immediate hypersensitivity. Many patients with asthma have other manifestations of atopy, such as rhinitis or eczema. Even among non-atopic patients with asthma, the pathophysiology of airway constriction is similar, raising the hypothesis that alternative mechanisms of mast cell degranulation may underlie the disease. The primary inflammatory lesion of asthma consists of accumulation of CD4(+) T helper type 2 (TH2) lymphocytes and eosinophils in the airway mucosa. TH2 cells orchestrate the asthmatic inflammation through the secretion of a series of cytokines, particularly interleukin 4 (IL-4), IL-13, IL-5, and IL-9. IL-4 is the major factor regulating IgE production by B cells, and is required for optimal TH2 differentiation. However, blocking IL-4 is not sufficient to inhibit the development of asthma in experimental models. In contrast, inhibition of IL-13, another TH2 cytokine whose signal transduction pathway overlaps with that of IL-4, completely blocks airway hyperreactivity in mouse asthma models. IL-5 is a key factor for eosinophilia and could therefore be responsible for some of the tissue damage seen in chronic asthma. IL-9 has pleiotropic activities on allergic mediators such as mast cells, eosinophils, B cells and epithelial cells, and might be a good target for therapeutic interventions. Finally, chemokines, which can be produced by many cell types from inflamed lungs, play a major role in recruiting the mediators of asthmatic inflammation. Genetic studies have demonstrated that multiple genes are involved in asthma. Several genome wide screens point to chromosome 5q31--33 as a major susceptibility locus for asthma and high IgE values. This region includes a cluster of cytokine genes, and genes encoding IL-3, IL-4, IL-5, IL-9, IL-13, granulocyte macrophage colony stimulating factor, and the beta chain of IL-12. Interestingly, for some of these cytokines, a linkage was also established between asthma and their receptor. Another susceptibility locus has been mapped on chromosome 12 in a region that contains other potential candidate cytokine genes, including the gene encoding interferon gamma, the prototypical TH1 cytokine with inhibitory activities for TH2 lymphocytes. Taken together, both experimental and genetic studies point to TH2 cytokines, such as IL-4, IL-13, IL-5, and IL-9, as important targets for therapeutic applications in patients with asthma.
    背景与目标: : 哮喘是间歇性气道阻塞,支气管平滑肌细胞对支气管收缩剂的高反应性和慢性支气管炎症的三联征。从病因学的角度来看,哮喘是一种异质性疾病,但通常以即刻超敏反应的形式出现。许多哮喘患者有特应性的其他表现,如鼻炎或湿疹。即使在非特应性哮喘患者中,气道收缩的病理生理也相似,这提出了肥大细胞脱颗粒的替代机制可能是该疾病的基础的假设。哮喘的主要炎性病变包括气道粘膜中CD4 () T辅助2型 (TH2) 淋巴细胞和嗜酸性粒细胞的积累。TH2细胞通过分泌一系列细胞因子,特别是白介素4 (IL-4),IL-13,IL-5和IL-9来协调哮喘炎症。IL-4是调节b细胞产生IgE的主要因子,是最佳TH2分化所必需的。然而,在实验模型中,阻断IL-4不足以抑制哮喘的发展。相反,抑制IL-13 (另一种TH2细胞因子的信号转导途径与IL-4的信号转导途径重叠) 完全阻断了小鼠哮喘模型中的气道高反应性。IL-5是嗜酸性粒细胞增多的关键因素,因此可能是慢性哮喘中某些组织损伤的原因。IL-9对肥大细胞,嗜酸性粒细胞,b细胞和上皮细胞等过敏介质具有多效性,可能是治疗干预的良好靶标。最后,趋化因子可以由发炎的肺部产生的许多细胞类型产生,在募集哮喘炎症介质中起主要作用。遗传学研究表明,多种基因与哮喘有关。几个基因组宽筛选显示5q31 -- 33号染色体是哮喘和高IgE值的主要易感位点。该区域包括细胞因子基因簇,以及编码IL-3,IL-4,IL-5,IL-9,IL-13,粒细胞巨噬细胞集落刺激因子和IL-12 β 链的基因。有趣的是,对于其中一些细胞因子,哮喘和它们的受体之间也建立了联系。另一个易感性基因座已定位在12号染色体上,该区域包含其他潜在的候选细胞因子基因,包括编码干扰素 γ 的基因,干扰素 γ 是对TH2淋巴细胞具有抑制活性的原型TH1细胞因子。总之,实验和遗传学研究都指出,TH2细胞因子 (例如IL-4,IL-13,IL-5和IL-9) 是哮喘患者治疗应用的重要靶标。
  • 【习惯性运动对肥胖Zucker大鼠巨噬细胞eHsp72-induced释放炎性细胞因子的影响。】 复制标题 收藏 收藏
    DOI:10.1055/s-0032-1327650 复制DOI
    作者列表:Garcia JJ,Martin-Cordero L,Hinchado MD,Bote ME,Ortega E
    BACKGROUND & AIMS: :Regular exercise is a good non-pharmacological treatment of metabolic syndrome in that it improves obesity, diabetes, and inflammation. The 72 kDa extracellular heat shock protein (eHsp72) is released during exercise, thus stimulating the inflammatory responses. The aim of the present work was to evaluate the effect of regular exercise on the eHsp72-induced release of IL-1β, IL-6, and TNFα by macrophages from genetically obese Zucker rats (fa/fa) (ObZ), using lean Zucker (LZ) rats (Fa/fa) to provide reference values. ObZ presented a higher plasma concentration of eHsp72 than LZ, and exercise increased that concentration. In response to eHsp72, the macrophages from ObZ released less IL-1β and TNFα, but more IL-6, than macrophages from LZ. While eHsp72 stimulated the release of IL-1β, TNFα, and IL-6 in the macrophages from healthy LZ (with respect to the constitutive release), it inhibited the release of IL-1β and IL-6 in macrophages from ObZ. The habitual exercise improved the release of inflammatory cytokines by macrophages from ObZ in response to eHsp72 (it increased IL-1β and TNFα, and decreased IL-6), tending to values closer to those determined in healthy LZ. A deregulated macrophage inflammatory and stress response induced by eHsp72 underlies MS, and this is improved by habitual exercise.
    背景与目标: : 定期运动是代谢综合征的一种很好的非药物治疗方法,因为它可以改善肥胖,糖尿病和炎症。在运动过程中释放72 kDa的细胞外热休克蛋白 (eHsp72),从而刺激炎症反应。本工作的目的是评估定期运动对遗传肥胖Zucker大鼠 (fa/fa) (ObZ) 巨噬细胞eHsp72-induced释放IL-1β,IL-6和tnf α 的影响,使用精益Zucker (LZ) 大鼠 (Fa/fa) 提供参考值。ObZ的eHsp72血浆浓度高于LZ,运动增加了该浓度。响应eHsp72,来自ObZ的巨噬细胞比来自LZ的巨噬细胞释放更少的IL-1β 和tnf α,但更IL-6。虽然eHsp72刺激了健康LZ中巨噬细胞中IL-1β,tnf α 和IL-6的释放 (相对于组成型释放),但它抑制了ObZ中巨噬细胞中IL-1β 和IL-6的释放。习惯性运动改善了巨噬细胞对eHsp72的响应从ObZ释放的炎性细胞因子 (它增加了IL-1β 和tnf α,并降低了IL-6),趋向于接近健康LZ中确定的值。由eHsp72引起的巨噬细胞炎症和应激反应失调是MS的基础,而习惯性运动可以改善这种反应。
  • 【干扰素 β-1治疗下多发性硬化患者Th17-related细胞因子和受体的评价。】 复制标题 收藏 收藏
    DOI:10.1016/j.jneuroim.2012.10.009 复制DOI
    作者列表:Esendagli G,Kurne AT,Sayat G,Kilic AK,Guc D,Karabudak R
    BACKGROUND & AIMS: :Th17-related cytokines (IL-17, IL-23, and IL-26) and receptors (IL-17R and IL-23R) were evaluated in MS patients under immunomodulatory IFN-β1 therapy during a 2year follow-up. Before the initiation of treatment, no significant difference was found in cytokine or receptor expression between controls and MS patients. Of the three cytokines evaluated, IL-26 was the highest in the patients' sera. The amount of IL-17 and CD13(+)IL-17R(+) cells was steadily decreased whereas IL-23 and IL-26 levels were gradually increased with IFN-β1 therapy. The patients in progressive phase had very high levels of IL-17. Th17-associated parameters should be considered in the immunomodulatory IFN-β1 therapy of MS.
    背景与目标: : 在2年的随访中,在免疫调节IFN-β1治疗的MS患者中评估了Th17-related细胞因子 (IL-17,IL-23和IL-26) 和受体 (IL-17R和IL-23R)。在开始治疗之前,对照组和MS患者之间的细胞因子或受体表达没有发现显着差异。在评估的三种细胞因子中,IL-26在患者血清中最高。IFN-β1治疗后,IL-17和CD13(+)IL-17R(+) 细胞的数量稳步下降,而IL-23和IL-26水平逐渐上升。进展期患者的IL-17水平非常高。在MS的免疫调节IFN-β1治疗中应考虑Th17-associated参数。
  • 【非典型分枝杆菌 (分枝杆菌,分枝杆菌) 的脐带因子刺激结核病中某些相关的促炎细胞因子的分泌。】 复制标题 收藏 收藏
    DOI:10.1099/mic.0.060681-0 复制DOI
    作者列表:Linares C,Bernabéu A,Luquin M,Valero-Guillén PL
    BACKGROUND & AIMS: :The ability to induce several cytokines relevant to tuberculosis (TNF-α, IL-1β, IL-6, IL-12p40 and IL-23) by cord factor (trehalose dimycolate) from Mycobacterium alvei CR-21(T) and Mycobacterium brumae CR-270(T) was studied in the cell lines RAW 264.7 and THP-1, and compared to the ability of cord factor from Mycobacterium tuberculosis H37Rv, where this glycolipid appears to be implicated in the pathogenesis of tuberculosis. Details of the fine structure of these molecules were obtained by NMR and MS. The mycoloyl residues were identified as α and (ω-1)-methoxy in M. alvei CR-21(T) and α in M. brumae CR-270(T); in both cases they were di-unsaturated instead of cyclopropanated as found in M. tuberculosis. In RAW 264.7 cells, cord factors from M. alvei CR-21(T), M. brumae CR-270(T) and M. tuberculosis differed in their ability to stimulate IL-6, the higher levels corresponding to the cord factor from M. tuberculosis. In THP-1 cells, a similar overall profile of cytokines was found for M. alvei CR-21(T) and M. brumae CR-270(T), with high proportions of IL-1β and TNF-α, and different from M. tuberculosis, where IL-6 and IL-12p40 prevailed. The data obtained indicate that cord factors from the atypical mycobacteria M. alvei CR-21(T) and M. brumae CR-270(T) stimulated the secretion of several pro-inflammatory cytokines, although there were some differences with those of M. tuberculosis H37Rv. This finding seems to be due to their particular mycoloyl substituents and could be of interest when considering the potential adjuvanticity of these molecules.
    背景与目标: : 在细胞系原始264.7和THP-1中研究了脐带因子 (海藻糖二CR-270) 诱导几种与结核病相关的细胞因子 (TNF-α,IL-1β,IL-6,IL-12p40和IL-23) 的能力,与结核分枝杆菌H37Rv的脐带因子的能力相比,该糖脂似乎与结核病的发病机理有关。通过NMR和MS获得了这些分子的精细结构的详细信息。菌酰基残基在CR-21(T) 中被鉴定为 α 和 (ω-1)-甲氧基,而在CR-270(T) 中被鉴定为 α; 在这两种情况下,它们都是二不饱和的,而不是在结核分枝杆菌中发现的环丙烷。在原始264.7细胞中,来自肺泡CR-21(T),布鲁氏菌CR-270(T) 和结核分枝杆菌的脐带因子在刺激IL-6的能力上有所不同,较高水平对应于结核分枝杆菌的脐带因子。在THP-1细胞中,发现肺泡支原体CR-21(T) 和CR-270支原体 (T) 具有相似的细胞因子总体特征,IL-1β 和TNF-α 比例很高,与结核支原体不同,IL-6和IL-12p40盛行。获得的数据表明,来自非典型分枝杆菌CR-21(T) 和布鲁氏菌CR-270(T) 的脐带因子刺激了几种促炎细胞因子的分泌,尽管与结核分枝杆菌H37Rv有一些差异。这一发现似乎是由于它们特定的mycoloyl取代基,并且在考虑这些分子的潜在可调性时可能会引起关注。
  • 【高水平的热休克蛋白70与促炎性细胞因子相关,可以区分早发性和晚发性子痫前期。】 复制标题 收藏 收藏
    DOI:10.1016/j.jri.2013.08.003 复制DOI
    作者列表:Peraçoli JC,Bannwart-Castro CF,Romao M,Weel IC,Ribeiro VR,Borges VT,Rudge MV,Witkin SS,Peraçoli MT
    BACKGROUND & AIMS: :Preeclampsia (PE), a specific syndrome of pregnancy, can be classified into early and late onset, depending on whether clinical manifestations occur before or after 34 weeks' gestation. We determined whether plasma concentrations of Hsp60 and Hsp70 were related to circulating cytokine levels, as well as kidney and liver functions, in early- and late-onset PE. Two hundred and thirty-seven preeclamptic women (95 with early- and 142 with late-onset PE) were evaluated. Plasma levels of Hsp60, Hsp70, and their specific antibodies, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-10, IL-12, and soluble TNF-α-receptor I (sTNFRI) concentrations, were determined by enzyme-linked immunosorbent assay (ELISA). Concentrations of Hsp70, TNF-α, IL-1β, IL-12, and sTNFRI were significantly elevated in patients with early-onset PE compared with women with late-onset PE; IL-10 levels were significantly lower in the early-onset PE group. Concentrations of urea, uric acid, proteinuria, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and lactate dehydrogenase (LDH) were also significantly higher in early-onset PE. The percentage of infants with intrauterine growth restriction was also significantly higher in women with early-onset PE. There were positive correlations between Hsp70 levels and TNF-α, TNFRI, IL-1β, IL-12, GOT, GPT, LDH, and uric acid concentrations in early-onset PE group. Thus, early-onset PE was associated with greater maternal and fetal impairment. There are differences in pathophysiology between early- and late-onset PE, highlighting by the difference in Hsp70 levels.
    背景与目标: : 先兆子痫 (PE) 是一种特定的妊娠综合征,可分为早发和晚发,具体取决于临床表现是在妊娠34周之前还是之后发生。我们确定了早期和晚期PE中Hsp60和Hsp70的血浆浓度是否与循环细胞因子水平以及肾脏和肝脏功能有关。评估了二百三十七名先兆子痫妇女 (95例早发性PE和142例晚发性PE)。通过酶联免疫吸附测定 (ELISA) 测定血浆Hsp60,Hsp70及其特异性抗体,肿瘤坏死因子-α (TNF-α),白介素 (IL)-1,IL-10,IL-12和可溶性TNF-α 受体I (sTNFRI) 的浓度。与晚发PE患者相比,早发PE患者的Hsp70,TNF-α,IL-1β,IL-12和sTNFRI浓度显着升高; 早发PE组的IL-10水平显着降低。早发性PE的尿素,尿酸,蛋白尿,谷氨酸草酰乙酸转氨酶 (GOT),谷氨酸丙酮酸转氨酶 (GPT) 和乳酸脱氢酶 (LDH) 的浓度也显着较高。早发性PE的女性中,宫内生长受限的婴儿百分比也显着更高。早发性PE组Hsp70水平与TNF-α,TNFRI,IL-1β,IL-12,GOT,GPT,LDH和尿酸浓度呈正相关。因此,早发性PE与更大的母体和胎儿损害有关。早发性PE和晚发性PE之间的病理生理差异,突出表现为Hsp70水平的差异。
  • 【人骨髓脂肪细胞中瘦素表达的细胞因子调节。】 复制标题 收藏 收藏
    DOI:10.1055/s-2007-978658 复制DOI
    作者列表:Laharrague P,Truel N,Fontanilles AM,Corberand JX,Pénicaud L,Casteilla L
    BACKGROUND & AIMS: :Leptin is a hormone secreted by adipocytes. Besides controlling appetite and body weight, it has been suggested that leptin plays a role in inflammation and hemopoiesis. In this study we demonstrate that the pro-inflammatory/hemopoietic cytokines, IL-1beta, IL-6, TNF-alpha, and interferon-gamma, significantly inhibit gene expression and secretion of leptin by bone marrow adipocytes. These findings are in agreement with the data recently obtained from non-medullary adipose tissues. Within the bone marrow environment, leptin regulation by these pleiotropic cytokines could contribute to controlling the proliferation and differentiation of hemopoietic precursors as well as the maturation of stromal cells.
    背景与目标: : 瘦素是一种由脂肪细胞分泌的激素。除了控制食欲和体重外,还表明瘦素在炎症和造血中起作用。在这项研究中,我们证明了促炎/造血细胞因子IL-1beta,IL-6,TNF-α 和干扰素-γ 显着抑制骨髓脂肪细胞的基因表达和瘦素分泌。这些发现与最近从非髓脂肪组织获得的数据一致。在骨髓环境中,这些多效性细胞因子对瘦素的调节可能有助于控制造血前体的增殖和分化以及基质细胞的成熟。
  • 【Galectin-3与细胞表面糖蛋白CD146 (MCAM,MUC18) 相互作用,并诱导血管内皮细胞分泌促进转移的细胞因子。】 复制标题 收藏 收藏
    DOI:10.1074/jbc.M117.783431 复制DOI
    作者列表:Colomb F,Wang W,Simpson D,Zafar M,Beynon R,Rhodes JM,Yu LG
    BACKGROUND & AIMS: :The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans. We have shown previously that circulating galectin-3, which is increased up to 30-fold in cancer patients, promotes blood-borne metastasis in an animal cancer model. This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines. Here we sought to identify the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion. Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells. CD146 was the major galectin-3-binding ligand and strongly co-localized with galectin-3 on endothelial cell surfaces treated with exogenous galectin-3. Moreover, galectin-3 bound to N-linked glycans on CD146 and induced CD146 dimerization and subsequent activation of AKT signaling. siRNA-mediated suppression of CD146 expression completely abolished the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells. Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines. We conclude that CD146/MCAM interactions with circulating galectin-3 may have an important influence on cancer progression and metastasis.
    背景与目标: : 半乳糖苷结合蛋白galectin-3通过与各种半乳糖苷末端聚糖的相互作用,越来越被认为是癌症发展,进展和转移的重要参与者。我们先前已经证明,在动物癌症模型中,循环galectin-3在癌症患者中增加了30倍,可促进血源性转移。这种作用部分归因于galectin-3与血管内皮细胞上未知受体的相互作用,并引起内皮分泌几种促进转移的细胞因子。在这里,我们试图鉴定内皮细胞表面负责galectin-3-mediated细胞因子分泌的galectin-3-binding分子。使用两种不同的galectin-3亲和纯化过程,我们从血管内皮细胞中提取了四种细胞膜糖蛋白,CD146/黑色素瘤细胞粘附分子 (MCAM)/MUC18,CD31/血小板内皮细胞粘附分子-1 (PECAM-1),CD144/VE-钙粘蛋白和CD106/Endoglin。CD146是主要的galectin-3-binding配体,与galectin-3强烈共定位在用外源galectin-3处理的内皮细胞表面上。此外,galectin-3与CD146上的N-连接聚糖结合并诱导CD146二聚化和随后AKT信号传导的激活。siRNA介导的CD146表达抑制完全消除了内皮细胞galectin-3-induced分泌IL-6和g-csf细胞因子。因此,CD146/MCAM是内皮细胞表面的功能性galectin-3-binding配体,负责galectin-3-induced分泌促进转移的细胞因子。我们得出结论,CD146/MCAM与循环galectin-3的相互作用可能对癌症的进展和转移有重要影响。

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