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61.
T R Mosmann T Yokota R Kastelein S M Zurawski N Arai Y Takebe 《Journal of immunology (Baltimore, Md. : 1950)》1987,138(6):1813-1816
Mouse and human interleukin 2 (IL 2) both cause proliferation of T cells of the homologous species at high efficiency. Human IL 2 also stimulates proliferation of mouse T cells at similar concentrations, whereas mouse IL 2 stimulates human T cells at a lower (sixfold to 170-fold) efficiency. In contrast, the T cell stimulating activities of mouse and human B cell stimulatory factor 1 (interleukin 4; IL 4) appear to be species specific over the range of concentrations tested; we detected no activity of mouse IL 4 on human T cells, or human IL 4 on mouse T cells. 相似文献
62.
63.
The amino-terminal helix of GM-CSF and IL-5 governs high affinity binding to their receptors. 总被引:16,自引:7,他引:9 下载免费PDF全文
Transduction of the biological effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-5 (IL-5) requires the interaction of each cytokine with at least two cell surface receptor components, one of which is shared between these two cytokines. A strategy is presented that allowed us to identify receptor binding determinants in GM-CSF and IL-5. Mixed species (human and mouse) receptors were used to locate unique receptor binding domains on a series of human-mouse hybrid GM-CSF and IL-5 cytokines. Results show that the interaction of these two cytokines with the shared subunit of their high affinity receptor complexes is governed by a very small part of their peptide chains. The presence of a few key residues in the amino-terminal alpha-helix of each ligand is sufficient to confer specificity to the interaction. Comparison with other cytokines suggests that the amino-terminal helix of many of these proteins may contain the recognition element for the formation of high affinity binding sites with the alpha subunit of their multi-component receptors. 相似文献
64.
Trypanosomatid flagellates (Phytomonas sp.) were detected in the sieve tubes of ‘hartrot'-diseased coconut palms (Cocos nucifera) and in the laticifers of Cecropia palmata and Euphorbia hirta plants occurring as weeds in and around coconut plantations with diseased palms. The possible interrelationship and transmission by insect vectors of these protozoa is discussed. 相似文献
65.
Robert Greenberg Daniel Lundell Yair Alroy Susan Bonitz Russell Condon James Fossetta Beth Frommer Keith Gewain Mitchell Katz Paul J. Leibowitz Dr. satwant K. Narula Robert Kastelein Anita Van Kimmenade 《Current microbiology》1988,17(6):321-332
Human granulocyte-macrophage colony stimulating factor (HuGM-CSF) was expressed periplasmically inEscherichia coli with the secretory vector, pINIIIompA2 [10]. HuGM-CSF protein thus expressed was shown to be faithfully cleaved and biologically active. This protein, however, could not be released by osmotic shock and, on subcellular fractionation, co-sedimented with the outer membrane fraction. The effect of promoters, vectors, host strains, induction conditions and media formulation on expression levels was also evaluated. Some of these factors play a significant role in determining maximal achievable levels of HuGM-CSF in the secretory expression system ofE. coli.Both may be considered first authors. 相似文献
66.
Philip J. Barter Kerry-Anne Rye Mohan S. Beltangady William C. Ports William T. Duggan S. Matthijs Boekholdt David A. DeMicco John J. P. Kastelein Charles L. Shear 《Journal of lipid research》2012,53(11):2436-2442
Development of the cholesteryl ester transfer protein (CETP) inhibitor, torcetrapib, was halted after the ILLUMINATE trial revealed an increase in both all-cause mortality (ACM) and major cardiovascular events (MCVEs) associated with its use. We now report that the harm caused by torcetrapib was confined to those in the 10 mg atorvastatin subgroup for both ACM [hazard ratio (HR) = 2.68, 95% CI (1.58, 4.54), P < 0.0001] and MCVEs [HR = 1.41, 95% CI (1.14, 1.74), P = 0.002], with no evidence of harm when torcetrapib was coadministered with higher doses of atorvastatin. In the atorvastatin 10 mg subgroup, age, prior heart failure and stroke were significantly associated with ACM, independent of torcetrapib treatment, whereas low apoA-I, smoking, hypertension, heart failure, myocardial infarction, and stroke were independently associated with MCVEs. After adjusting for these factors, the HR associated with torcetrapib treatment in the 10 mg atorvastatin subgroup remained elevated for both ACM [HR = 2.67, 95% CI (1.57, 4.54), P < 0.001] and MCVE [HR = 1.36, 95% CI (1.10, 1.69), P = 0.005]. Thus, the harm caused by torcetrapib was confined to individuals taking atorvastatin 10 mg. The harm could not be explained by torcetrapib-induced changes in lipid levels, blood pressure, or electrolytes. It is conceivable that higher doses of atorvastatin protected against the harm caused by torcetrapib. 相似文献
67.
Huijgen R Fouchier SW Denoun M Hutten BA Vissers MN Lambert G Kastelein JJ 《Journal of lipid research》2012,53(5):979-983
The extent of hypercholesterolemia varies considerably in patients with familial hypercholesterolemia (FH). We hypothesized that the variability of the FH phenotype might be partly explained by variation in proprotein convertase subtilisin kexin type 9 (PCSK9) activity. Individuals between 18 and 53 years of age who had been tested for a pathogenic LDLR or APOB mutation were eligible. Mutation carriers with a LDL-C level below the 75(th) percentile (called "FH low") were selected, as well as those with LDL-C above the 90(th) percentile (called "FH high"). Relatives who tested negative for the mutation were the "controls." PCSK9 plasma levels were assessed in 267 individuals who did not receive cholesterol-lowering treatment at the time of the study. Mean PCSK9 plasma levels (95% CI) were lower in the FH-low group compared with the FH-high group [152 (137-167) ng/ml vs. 186 (165-207) ng/ml, P = 0.010] and the control group [177 (164-190) ng/ml, P = 0.013]. Mean PCSK9 levels did not statistically differ between the FH-high and control groups (P = 0.50). Plasma PCSK9 levels are positively associated with LDL-C levels in FH patients and might contribute to the phenotypic severity in this disorder. Therefore, the results of pharmaceutical inhibition of PCSK9 in FH patients are eagerly awaited. 相似文献
68.
Kleinschek MA Muller U Brodie SJ Stenzel W Kohler G Blumenschein WM Straubinger RK McClanahan T Kastelein RA Alber G 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(2):1098-1106
IL-23, a heterodimeric cytokine composed of the p40 subunit of IL-12 and a novel p19 subunit, has been shown to be a key player in models of autoimmune chronic inflammation. To investigate the role of IL-23 in host resistance during chronic fungal infection, wild-type, IL-12- (IL-12p35-/-), IL-23- (IL-23p19-/-), and IL-12/IL-23- (p40-deficient) deficient mice on a C57BL/6 background were infected with Cryptococcus neoformans. Following infection, p40-deficient mice demonstrated higher mortality than IL-12p35-/- mice. Reconstitution of p40-deficient mice with rIL-23 prolonged their survival to levels similar to IL-12p35-/- mice. IL-23p19-/- mice showed a moderately reduced survival time and delayed fungal clearance in the liver. Although IFN-gamma production was similar in wild-type and IL-23p19-/- mice, production of IL-17 was strongly impaired in the latter. IL-23p19-/- mice produced fewer hepatic granulomata relative to organ burden and showed defective recruitment of mononuclear cells to the brain. Moreover, activation of microglia cells and expression of IL-1beta, IL-6, and MCP-1 in the brain was impaired. These results show that IL-23 complements the more dominant role of IL-12 in protection against a chronic fungal infection by an enhanced inflammatory cell response and distinct cytokine regulation. 相似文献
69.
IL-27 limits IL-2 production during Th1 differentiation 总被引:7,自引:0,他引:7
Villarino AV Stumhofer JS Saris CJ Kastelein RA de Sauvage FJ Hunter CA 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(1):237-247
Although the ability of IL-27 to promote T cell responses is well documented, the anti-inflammatory properties of this cytokine remain poorly understood. The current work demonstrates that during infection with Toxoplasma gondii, IL-27R-deficient mice generate aberrant IL-2 responses that are associated with the development of a lethal inflammatory disease. Because in vivo depletion of IL-2 prolongs the survival of infected IL-27R-/- mice, these data suggest that IL-27 curbs the development of immunopathology by limiting parasite-induced IL-2 production. Consistent with this hypothesis, IL-27R-/- CD4+ T cells produce more IL-2 than wild-type counterparts during in vitro differentiation, and when rIL-27 is introduced, it can suppress the expression of IL-2 mRNA and protein by the latter group. Additionally, these studies reveal that, like IL-27, IL-12 can inhibit IL-2 production, and although each employs distinct mechanisms, they can synergize to enhance the effect. In contrast, this property is not shared by closely related cytokines IL-6 and IL-23. Thus, while traditionally viewed as proinflammatory agents, the present findings establish that IL-27 and IL-12 cooperate to limit the availability of IL-2, a potent T cell growth and survival factor. Moreover, because the current studies demonstrate that both can induce expression of suppressor of cytokine signaling 3, a protein that tempers cytokine receptor signaling, they also suggest that IL-27 and IL-12 share additionally inhibitory properties. 相似文献
70.
Rakesh S. Birjmohun Menno Vergeer Erik S. G. Stroes Manjinder S. Sandhu Sally L. Ricketts Michael W. Tanck Nicholas J. Wareham J. Wouter Jukema John J. P. Kastelein Kay-Tee Khaw S. Matthijs Boekholdt 《PloS one》2009,4(8)