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101.
Siva A Xin H Qin F Oltean D Bowdish KS Kretz-Rommel A 《Cancer immunology, immunotherapy : CII》2008,57(7):987-996
Background and Objective Immune escape by tumors can occur by multiple mechanisms, each a significant barrier to immunotherapy. We previously demonstrated
that upregulation of the immunosuppressive molecule CD200 on chronic lymphocytic leukemia cells inhibits Th1 cytokine production
required for an effective cytotoxic T cell response. CD200 expression on human tumor cells in animal models prevents human
lymphocytes from rejecting the tumor; treatment with an antagonistic anti-CD200 antibody restored lymphocyte-mediated tumor
growth inhibition. The current study evaluated CD200 expression on solid cancers, and its effect on immune response in vitro.
Methods and Results CD200 protein was expressed on the surface of 5/8 ovarian cancer, 2/4 melanoma, 2/2 neuroblastoma and 2/3 renal carcinoma
cell lines tested, but CD200 was absent on prostate, lung, breast, astrocytoma, or glioblastoma cell lines. Evaluation of
patient samples by immunohistochemistry showed strong, membrane-associated CD200 staining on malignant cells of melanoma (4/4),
ovarian cancer (3/3) and clear cell renal cell carcinoma (ccRCC) (2/3), but also on normal ovary and kidney. CD200 expression
on melanoma metastases was determined by RT-QPCR, and was found to be significantly higher in jejunum metastases (2/2) and
lung metastases (2/6) than in normal samples. Addition of CD200-expressing, but not CD200-negative solid tumor cell lines
to mixed lymphocyte reactions downregulated the production of Th1 cytokines. Inclusion of antagonistic anti-CD200 antibody
restored Th1 cytokine responses.
Conclusion These data suggest that melanoma, ccRCC and ovarian tumor cells can express CD200, thereby potentially suppressing anti-tumor
immune responses. CD200 blockade with an antagonistic antibody may permit an effective anti-tumor immune response in these
solid tumor types. 相似文献
102.
103.
Simin Feng Zhuqing Dai Anna B. Liu Jinbao Huang Nihal Narsipur Grace Guo Bo Kong Kenneth Reuhl Wenyun Lu Zisheng Luo Chung S. Yang 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2018,1863(10):1274-1284
Objective
To investigate and compare the effects of two common dietary phytosterols, stigmasterol and β-sitosterol, in altering lipid metabolism and attenuating nonalcoholic fatty liver disease (NAFLD).Methods
Stigmasterol and β-sitosterol were administered to mice at 0.4% in a high-fat western-style diet (HFWD) for 17?weeks.Results
Stigmasterol and β-sitosterol significantly ameliorated HFWD-induced fatty liver and metabolic abnormalities, including elevated levels of hepatic total lipids, triacylglycerols, cholesterol and liver histopathology. Both phytosterols decreased the levels of intestinal bile acids, accompanied by markedly increased fecal lipid levels. In addition, they altered the expression of genes involved in lipid metabolism. β-Sitosterol was less effective in affecting most of these parameters. Lipidomic analysis of liver and serum samples showed that stigmasterol prevented the HFWD-induced elevation of some di- and triacylglycerol species and lowering of some phospholipid species. Stigmasterol also decreased serum levels of ceramides.Conclusion
Stigmasterol and β-sitosterol, at a dose corresponding to that suggested for humans by the FDA for lowering cholesterol levels, are shown to alleviate HFWD-induced NAFLD. Stigmasterol was more effective than β-sitosterol, possibly because of its suppression of hepatic lipogenic gene expression and modulation of circulating ceramide levels. 相似文献104.
Lipid droplets (LDs) are ubiquitous cellular organelles for lipid storage which are composed of a neutral lipid core bounded by a protein decorated phospholipid monolayer. Although lipid storage is their most obvious function, LDs are far from inert as they participate in maintaining lipid homeostasis through lipid synthesis, metabolism, and transportation. Furthermore, they are involved in cell signaling and other molecular events closely associated with human disease such as dyslipidemia, obesity, lipodystrophy, diabetes, fatty liver, atherosclerosis, and others. The last decade has seen a great increase in the attention paid to LD biology. Regardless, many fundamental features of LD biology remain obscure. In this review, we will discuss key aspects of LD biology including their biogenesis, growth and regression. We will also summarize the current knowledge about the role LDs play in human disease, especially from the perspective of the dynamics of the associated proteins. This article is part of a Special issue entitled Cardiac adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers. 相似文献
105.
Norton PA Comunale MA Krakover J Rodemich L Pirog N D'Amelio A Philip R Mehta AS Block TM 《Journal of cellular biochemistry》2008,104(1):136-149
The association between elevated circulating levels of GP73 (and fucosylated GP73 in particular) and hepatocellular carcinoma suggests that a thorough analysis of the extent of GP73 glycosylation is warranted. Detailed analysis of the glycosylation patterns of such low abundance proteins are hampered by technical difficulties. Using conventional lectin affinity chromatography, we have established that three quarters of the GP73 secreted from a cell line derived from HCC is fucosylated. Using mass spectrometry, we have established that at least two of three potential sites of N-linked glycosylation are occupied on most molecules of GP73 secreted from cultured hepatoma cells. Furthermore, the oligosaccharides added to recombinant GP73 resemble those present in the bulk of secreted protein, mostly bi-antennary with core fucose, with a smaller fraction of tri- and tetra-antennary structures. The frequency of fucosylation observed on the recombinant protein agrees well with the pattern of lectin binding of the endogenous secreted protein. Finally, we have developed a method to interrogate the glycans added to either the near full length protein or at a particular sequon, providing proof of concept that a small peptide embedded in a heterologous context can preserve both fucosylation and a high level of branching of oligosaccharides added. 相似文献
106.
Kawakami K Koguchi Y Qureshi MH Yara S Kinjo Y Miyazato A Nishizawa A Nariuchi H Saito A 《Microbiology and immunology》2000,44(12):1033-1041
In the present study, we examined the effect of soluble CD4 (sCD4) on host resistance and delayed-type hypersensitivity (DTH) response to Cryptococcus neoformans using a novel mutant mouse that exhibits a defect in the expression of membrane-bound CD4 but secretes high levels of sCD4 in the serum. In these mice, host resistance to this pathogen was impaired as indicated by an increased number of live pathogens in the lung. To elucidate the mechanism of immunodeficiency, three different sets of experiments were conducted. First, administration of anti-CD4 mAb restored the attenuated host defense. Second, in CD4 gene-disrupted (CD4KO) mice, host resistance was not attenuated compared to control mice. Third, implantation of sCD4 gene-transfected myeloma cells rendered the CD4KO mice susceptible to this infection, while similar treatment with mock-transfected cells did not show such an effect. These results indicated that immunodeficiency in the mutant mice was attributed to the circulating sCD4 rather than to the lack of CD4+ T cells. In addition, DTH response to C. neoformans evaluated by footpad swelling was reduced in the mutant mice compared to that in the control, and the reduced response was restored by the administration of anti-CD4 mAb. Finally, serum levels of IFN-gamma, IL-12 and IL-18 in the mutant mice were significantly reduced, while there was no difference in Th2 cytokines, such as IL-4 and IL-10. Considered collectively, our results demonstrated that sCD4 could directly prevent host resistance and DTH response to C. neoformans through interference with the production of Th1-type cytokines. 相似文献
107.
Seth S Maier MK Qiu Q Ravens I Kremmer E Förster R Bernhardt G 《Biochemical and biophysical research communications》2007,364(4):959-965
The CD155 ligand CD96 is an immunoglobulin-like protein tentatively allocated to the repertoire of human NK receptors. We report here that the CD96/CD155-interaction is preserved between man and mouse although both receptors are only moderately conserved in amino acid sequence. Moreover, murine CD96 (mCD96) binds to nectin-1, a receptor related to CD155. Applying newly generated monoclonal antibodies specifically recognizing mCD96, an expression profile is revealed resembling closely that of human CD96 (hCD96) on cells of hematopoietic origin. A panel of anti-mCD96 but also recently established anti-mCD155 antibodies effectively prevents formation of CD96/CD155-complexes. This was exploited to demonstrate that the only available receptor for mCD96 present on thymocytes is mCD155. Moreover, T cell adhesion to insect cells expressing mCD155 is blocked by these antibodies depending on the T cell subtype. These results suggest a function of the CD96/CD155-adhesion system in T cell biology. 相似文献
108.
本研究旨在寻找戊型肝炎病毒(hepatitis E virus,HEV)衣壳蛋白ORF2的相互作用蛋白,探讨其在HEV感染中的作用。采用酵母双杂交方法从人肝细胞文库中筛选与HEV ORF2相互作用的蛋白,结果显示CD63与HEV ORF2相互作用。Pull-down实验提示原核表达的ORF2与CD63结合较弱,而免疫共沉淀实验提示真核表达的ORF2能与CD63结合。流式细胞术检测结果显示,HEV易感细胞PLC/PRF/5细胞膜表面的CD63表达水平普遍低于HEV非易感细胞。过表达CD63抑制PLC/PRF/5细胞的HEV感染,而小干扰RNA(small interfering RNA,siRNA)干扰CD63表达则促进HEV感染。结果提示,CD63能与HEV ORF2相互作用,可能抑制HEV感染肝细胞。 相似文献
109.
Molecular model of the N-terminal receptor-binding domain of the human CD6 ligand ALCAM. 总被引:1,自引:1,他引:1
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J. Bajorath M. A. Bowen A. Aruffo 《Protein science : a publication of the Protein Society》1995,4(8):1644-1647
CD6-ligand interactions have been implicated in the regulation of T-cell adhesion and activation. CD6 is a member of the scavenger receptor family, whereas its human ligand (ALCAM) belongs to the immunoglobulin superfamily. The extracellular region of ALCAM includes five immunoglobulin-like domains. As a fusion protein, the N-terminal extracellular domain of ALCAM (ALCAMD1) binds specifically to CD6. We report the construction, assessment, and analysis of a molecular model of ALCAMD1. The model defines the CDR-analogous loops, the location of N-linked glycosylation sites, and residues that form the beta-sheet faces of the immunoglobulin-like domain. Predicted structural characteristics of the A'GFCC'C" face of the model are consistent with the presence of monomeric and dimeric forms of ALCAMD1, which has implications for the receptor-ligand interactions. 相似文献
110.
PEGylation of protein and peptide drugs is frequently used to improve in vivo efficacy. We investigated the action mechanism of tachyplesin I, a membrane-acting cyclic antimicrobial peptide from Tachypleus tridentatus and the effects of PEGylation on the mechanism. The PEGylated peptide induced the leakage of calcein from egg yolk l-α-phosphatidylglycerol/egg yolk l-α-phosphatidylcholine large unilamellar vesicles similarly to the parent peptide. Both peptides induced lipid flip-flop coupled to leakage and was translocated into the inner leaflet of the bilayer, indicating that tachyplesin I forms a toroidal pore and that PEGylation did not alter the basic mechanism of membrane permeabilization of the parent peptide. Despite their similar activities against model membranes, the peptides showed very different biological activities. The cytotoxicity of tachyplesin I was greatly reduced by PEGylation, although the antimicrobial activity was significantly weakened. We investigated the enhancement of the permeability of inner membranes induced by the peptides. Our results suggested that outer membranes and peptidoglycan layers play an inhibitory role in the permeation of the PEG moiety. Furthermore, a reduction in DNA binding by PEGylation may also contribute to the weak activity of the PEGylated peptide. 相似文献