Interleukin-18 （IL-18） was discovered as an interferon-y-inducing factor and had a critical role in inflammatory and immune respouse. It stimulates natural killer （NK） and T cells and enhances Thl immune response....Interleukin-18 （IL-18） was discovered as an interferon-y-inducing factor and had a critical role in inflammatory and immune respouse. It stimulates natural killer （NK） and T cells and enhances Thl immune response. These activated immune cells eliminate cancer cells and virus-infected cells effectively. However, IL-18 has also been found to promote tumor progression. Higher expression or secretion level of IL-18 is detected in various cancer cells in comparison with normal control, and IL-18 is able to induce angiogenesis, migration/metastasis, proliferation and immune escape. These dual effects and the mechanism of IL-18 need to be investigated further as it relates to cancer.展开更多
Brucella abortus is a zoonotic Gram-negative pathogen that causes brucelosis in ruminants and humans. Toll-like receptors （TLRs） recognize Brucella abortus and initiate antigen-presenting cell activities that affect...Brucella abortus is a zoonotic Gram-negative pathogen that causes brucelosis in ruminants and humans. Toll-like receptors （TLRs） recognize Brucella abortus and initiate antigen-presenting cell activities that affect both innate and adaptive immunity. In this study, we focused on recombinant Brucella cell-surface protein 31 （rBCSP31） to determine its effects on mouse macrophages. Our results demonstrated that rBCSP31 induced TNF-α, IL-6 and IL-12p40 production, which depended on the activation of mitogen-activated protein kinases （MAPKs） by stimulating the rapid phosphorylation of p38 and JNK and the activation of transcription factor NF-KB in macrophages. In addition, continuous exposure （〉24 h） of RAW264.7 cells to rBCSP31 significantly enhanced I FN-y-induced expression of MHC-II and the ability to present rBCSP31 peptide to CD4＋ T cells. Furthermore, we found that rBCSP31 could interact with both TLR2 and TLR4. The rBCSP31-induced cytokine production by macrophages from TLR2-/- and TLR4-/- mice was lower than that from C57BL/6 macrophages, and the activation of NF-KB and MAPKs was attenuated in macrophages from TLR2-/- and TLR4-/- mice. In addition, CD4＋ T cells from C57BL/6 mice immunized with rBCSP31 produced higher levels of IFN-y and IL-2 compared with CD4＋ T cells from TLR2-/- and TLR4-/- mice. Macrophages from immunized C57BL/6 mice produced higher levels of IL-12p40 than those from TLR2-/- and TLR4-/- mice. Furthermore, immunization with rBCSP31 provided better protection in C57BL/6 mice than in TLR2-/- and TLR4-/- mice after B. abortus 2308 challenge. These results indicate that rBCSP31 is a TLR2 and TLR4 agonist that induces cytokine production, upregulates macrophage function and induces the Thl immune response.展开更多
目的研究黄芪皂苷Ⅰ的免疫调节作用以及作用的分子机理。方法构建丝裂原诱导脾淋巴细胞增殖细胞模型,测定黄芪皂苷Ⅰ对Con A诱导T淋巴细胞增殖和LPS诱导B淋巴细胞增殖反应,构建anti-CD3 m Ab抗体诱导T淋巴细胞增殖,RT-PCR检测黄芪皂苷Ⅰ...目的研究黄芪皂苷Ⅰ的免疫调节作用以及作用的分子机理。方法构建丝裂原诱导脾淋巴细胞增殖细胞模型,测定黄芪皂苷Ⅰ对Con A诱导T淋巴细胞增殖和LPS诱导B淋巴细胞增殖反应,构建anti-CD3 m Ab抗体诱导T淋巴细胞增殖,RT-PCR检测黄芪皂苷Ⅰ对IL-2、IFN-γ和T-bet mRNA基因表达。结果黄芪皂苷Ⅰ在30n M显著促进Con A刺激T淋巴细胞增殖,差异有显著性意义(P<0.05);黄芪皂苷Ⅰ体外用药能够显著上调IFN-γ,T-bet的mRNA表达,而对IL-2表达水平无明显影响。结论黄芪皂苷Ⅰ可能特异性激活转录因子T-bet的转录,促进T淋巴细胞增殖和细胞因子的产生。展开更多
文摘Interleukin-18 （IL-18） was discovered as an interferon-y-inducing factor and had a critical role in inflammatory and immune respouse. It stimulates natural killer （NK） and T cells and enhances Thl immune response. These activated immune cells eliminate cancer cells and virus-infected cells effectively. However, IL-18 has also been found to promote tumor progression. Higher expression or secretion level of IL-18 is detected in various cancer cells in comparison with normal control, and IL-18 is able to induce angiogenesis, migration/metastasis, proliferation and immune escape. These dual effects and the mechanism of IL-18 need to be investigated further as it relates to cancer.
文摘Brucella abortus is a zoonotic Gram-negative pathogen that causes brucelosis in ruminants and humans. Toll-like receptors （TLRs） recognize Brucella abortus and initiate antigen-presenting cell activities that affect both innate and adaptive immunity. In this study, we focused on recombinant Brucella cell-surface protein 31 （rBCSP31） to determine its effects on mouse macrophages. Our results demonstrated that rBCSP31 induced TNF-α, IL-6 and IL-12p40 production, which depended on the activation of mitogen-activated protein kinases （MAPKs） by stimulating the rapid phosphorylation of p38 and JNK and the activation of transcription factor NF-KB in macrophages. In addition, continuous exposure （〉24 h） of RAW264.7 cells to rBCSP31 significantly enhanced I FN-y-induced expression of MHC-II and the ability to present rBCSP31 peptide to CD4＋ T cells. Furthermore, we found that rBCSP31 could interact with both TLR2 and TLR4. The rBCSP31-induced cytokine production by macrophages from TLR2-/- and TLR4-/- mice was lower than that from C57BL/6 macrophages, and the activation of NF-KB and MAPKs was attenuated in macrophages from TLR2-/- and TLR4-/- mice. In addition, CD4＋ T cells from C57BL/6 mice immunized with rBCSP31 produced higher levels of IFN-y and IL-2 compared with CD4＋ T cells from TLR2-/- and TLR4-/- mice. Macrophages from immunized C57BL/6 mice produced higher levels of IL-12p40 than those from TLR2-/- and TLR4-/- mice. Furthermore, immunization with rBCSP31 provided better protection in C57BL/6 mice than in TLR2-/- and TLR4-/- mice after B. abortus 2308 challenge. These results indicate that rBCSP31 is a TLR2 and TLR4 agonist that induces cytokine production, upregulates macrophage function and induces the Thl immune response.
