Background： Inflammation is often linked with the progress and poor outcome of lung cancer. The understanding of the relationship between tumor-associated macrophages （TAMs） and lung cancer cells involves in the un...Background： Inflammation is often linked with the progress and poor outcome of lung cancer. The understanding of the relationship between tumor-associated macrophages （TAMs） and lung cancer cells involves in the underlying mechanism of inflammatory cytokine production. Toll-like receptors （TLRs） are engaged in promoting the production of pro-inflammatory cytokines and play an important role in tumor immunology. Methods： To investigate the mechanisms by which TAMs influence the production of pro-inflammatory cytoldnes in lung cancer cells, we established an in vitro coculture system using TAMs and human non- small cell lung cancer （NSCLC） cell line SPC-A1. Levels of interleukin （IL）-113, IL-6 and IL-8 in SPC-A1 were evaluated by RT-PCR and cytometric bead array assay after being cocultured with TAMs. Expression changes of TLRs and TLRs signaling pathway proteins in SPC-Al were further confirmed by RT-PCR and western blot. The level changes of IL-1β, IL-6 and IL-8 in SPC-Al were also detected after the stimulation of TLRs agonists. Results： We found that the phenotype markers of TAMs were highly expressed after stimulating human monocyte cell line THP-1 by phorbol-12-myristate-β-acetate （PMA）. Higher mRNA and supernate secretion levels of IL-1β, IL-6 and IL-8 were detected in SPC-A1 after being eocultured with TAMs. We also found that TLR1, TLR6 and TLR7 were up-regulated in SPC-A1 in the coculture system with TAMs. Meanwhile, TLRs signaling pathway proteins were also significantly activated. Moreover, pre-treatment with agonist ligands for TLR1, TLR6 and TLR7 could dramatically promote inductions of IL-1β, IL-6 and IL-8. Conclusions： These findings demonstrated that TAMs may enhance IL-1β, IL-6 and IL-8 expressions via TLRs signaling pathway. We conclude that TAMs contribute to maintain the inflammation microenvironment and ultimately promote the development and progression of lung cancer.展开更多
牙周炎是由牙菌斑微生物引起的慢性感染性疾病。菌斑刺激引发宿主的免疫炎性反应,最终导致牙周支持组织的破坏。牙周炎是极其复杂且多因素参与的疾病,与许多系统性疾病具有双向影响。Toll样受体(Toll like receptors,TLRs)作为一类病原...牙周炎是由牙菌斑微生物引起的慢性感染性疾病。菌斑刺激引发宿主的免疫炎性反应,最终导致牙周支持组织的破坏。牙周炎是极其复杂且多因素参与的疾病,与许多系统性疾病具有双向影响。Toll样受体(Toll like receptors,TLRs)作为一类病原体模式识别受体,能够通过识别病原体相关分子模式激活固有免疫系统,刺激信号级联反应导致前致炎因子和生物调节因子的产生。研究显示TLRs在维持牙周健康及牙周病的发生发展中发挥着重要作用。本文就TLRs与牙周疾病的相关性研究作一综述。展开更多
目的研究低密度脂蛋白(LDL)氧化对人单核细胞源巨噬细胞Toll样受体-4(TLR-4)表达的影响及其机制。方法用RPM I 1640培养基体外培养人THP-1单核细胞系,加入佛波醇肉豆蔻酸乙酸酯(PMA)培养48 h使其分化为巨噬细胞,加入氧化低密度脂蛋白(Ox...目的研究低密度脂蛋白(LDL)氧化对人单核细胞源巨噬细胞Toll样受体-4(TLR-4)表达的影响及其机制。方法用RPM I 1640培养基体外培养人THP-1单核细胞系,加入佛波醇肉豆蔻酸乙酸酯(PMA)培养48 h使其分化为巨噬细胞,加入氧化低密度脂蛋白(Ox-LDL)或LDL,用免疫细胞化学、蛋白质免疫印迹和反转录聚合酶链反应(RT-PCR)方法,观察脂蛋白氧化前、后对巨噬细胞表达TLR-4蛋白及TLR-4 mRNA的影响。结果Ox-LDL可提高TLR-4蛋白及TLR-4 mRNA的表达(P<0.01);而LDL对TLR-4蛋白及其mRNA的表达无影响(P<0.05)。结论LDL的氧化可能促进THP-1源巨噬细胞TLR-4转录水平的上调,导致蛋白质的合成增加;Ox-LDL可能是动脉粥样硬化中炎症的始发原因之一。展开更多
基金the technical support from National Key Clinical Department of Laboratory Medicine of Jiangsu Province Hospitalsupported by National Natural Science Foundation of China(No. 81272324,81371894)+1 种基金Key Laboratory for Medicine of Jiangsu Province of China(No.XK201114)project funded by the Priority Academic Program Development ofJiangsu Higher Education Institutions
文摘Background： Inflammation is often linked with the progress and poor outcome of lung cancer. The understanding of the relationship between tumor-associated macrophages （TAMs） and lung cancer cells involves in the underlying mechanism of inflammatory cytokine production. Toll-like receptors （TLRs） are engaged in promoting the production of pro-inflammatory cytokines and play an important role in tumor immunology. Methods： To investigate the mechanisms by which TAMs influence the production of pro-inflammatory cytoldnes in lung cancer cells, we established an in vitro coculture system using TAMs and human non- small cell lung cancer （NSCLC） cell line SPC-A1. Levels of interleukin （IL）-113, IL-6 and IL-8 in SPC-A1 were evaluated by RT-PCR and cytometric bead array assay after being cocultured with TAMs. Expression changes of TLRs and TLRs signaling pathway proteins in SPC-Al were further confirmed by RT-PCR and western blot. The level changes of IL-1β, IL-6 and IL-8 in SPC-Al were also detected after the stimulation of TLRs agonists. Results： We found that the phenotype markers of TAMs were highly expressed after stimulating human monocyte cell line THP-1 by phorbol-12-myristate-β-acetate （PMA）. Higher mRNA and supernate secretion levels of IL-1β, IL-6 and IL-8 were detected in SPC-A1 after being eocultured with TAMs. We also found that TLR1, TLR6 and TLR7 were up-regulated in SPC-A1 in the coculture system with TAMs. Meanwhile, TLRs signaling pathway proteins were also significantly activated. Moreover, pre-treatment with agonist ligands for TLR1, TLR6 and TLR7 could dramatically promote inductions of IL-1β, IL-6 and IL-8. Conclusions： These findings demonstrated that TAMs may enhance IL-1β, IL-6 and IL-8 expressions via TLRs signaling pathway. We conclude that TAMs contribute to maintain the inflammation microenvironment and ultimately promote the development and progression of lung cancer.
文摘牙周炎是由牙菌斑微生物引起的慢性感染性疾病。菌斑刺激引发宿主的免疫炎性反应,最终导致牙周支持组织的破坏。牙周炎是极其复杂且多因素参与的疾病,与许多系统性疾病具有双向影响。Toll样受体(Toll like receptors,TLRs)作为一类病原体模式识别受体,能够通过识别病原体相关分子模式激活固有免疫系统,刺激信号级联反应导致前致炎因子和生物调节因子的产生。研究显示TLRs在维持牙周健康及牙周病的发生发展中发挥着重要作用。本文就TLRs与牙周疾病的相关性研究作一综述。
