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排序方式: 共有1722条查询结果,搜索用时 15 毫秒
1.
A. Datta R. David S. Glennie D. Scott E. Cernuda-Morollon R. I. Lechler A. J. Ridley F. M. Marelli-Berg 《American journal of transplantation》2006,6(12):2871-2883
The best-characterized mechanism of the action of immunosuppressive drugs is to prevent T-cell clonal expansion, thus containing the magnitude of the ensuing immune response. As T-cell recruitment to the inflammatory site is another key step in the development of T-cell-mediated inflammation, we analyzed and compared the effects of two commonly used immunosuppressants, cyclosporin A (CsA) and the rapamycin-related compound SDZ-RAD, on the motility of human CD4+ T cells. We show that CsA, but not SDZ-RAD, inhibits T-cell transendothelial migration in vitro. CsA selectively impaired chemokine-induced T-cell chemotaxis while integrin-mediated migration was unaffected. The inhibition of T-cell chemotaxis correlated with reduced AKT/PKB but not ERK activation following exposure to the chemokine CXCL-12/SDF-1. In addition, CsA, but not SDZ-RAD, prevents some T-cell receptor-mediated effects on T-cell motility. Finally, we show that CsA, but not SDZ-RAD inhibits tissue infiltration by T cells in vivo. Our data suggest a prominent antiinflammatory role for CsA in T-cell-mediated tissue damage, by inhibiting T-cell trafficking into tissues in addition to containing clonal expansion. 相似文献
2.
Background The role of IgE in airway hyperreaetivity is obscure. Objective In order to clarify the role of IgE in airway hyperreactivity, we investigated the effect of anti-IL-4 monoclonal antibody, rapamycin and interferon-γ on the antigen-induced IgE response, airway eosinophilia and hyperreactivity in mice. Methods Mice were immunized with an antigen (ovalbumin; OA) at intervals of 12 days. OA was inhaled 10 days after the secondary immunization. Twenty-four hours after the last inhalation, airway reactivity to acetylcholine was measured and bronchoalveolar lavage fluid (BALF) was obtained. Results Three inhalations of antigen caused an increase in the number of eosinophils in bronchoalveolar lavage fluid (BALF) and in airway hyperreactivity to acetylcholine with a significant elevation of serum IgE level. Anti-IL-4 at a dose of 1000 μg/animal and rapamycin at doses between 0.1 and 1 mg/kg inhibited the IgE production, but did not affect the airway eosinophilia or hyperreactivity to acetylcholine. In contrast, IFN-γ clearly inhibited the antigen-induced airway eosinophilia and hyperreactivity, but did not affect the IgE antibody production. Conclusion These results suggest that the inhibition of IgE production does not suppress the onset of airway hyperreactivity and eosinophilia in mice, and that IFN-γ inhibits the antigen-induced airway hyperreactivity, probably due to the inhibition of airway eosinophilia. 相似文献
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4.
《Journal of labelled compounds & radiopharmaceuticals》2006,49(10):849-856
Several isotopomers of ABT‐578 ( I , II , III , and IV ) were prepared starting from different labeled precursors: [5'‐3H]‐tetrazole ( 1 ), [5'‐14C]‐tetrazole ( 2 ), [40‐3H]rapamycin ( 3 ), and [2,11,31‐3H]rapamycin ( 4 ). It was shown that the tritium label at the 40 position of rapamycin is lost during an attempted synthesis of [40‐3H]ABT‐578 ( III ). Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
5.
Synergistic mechanisms by which sirolimus and cyclosporin inhibit rat heart and kidney allograft rejection 总被引:3,自引:0,他引:3 下载免费PDF全文
S M STEPKOWSKI L TIAN K L NAPOLI R GHOBRIAL M E WANG T C CHOU B D KAHAN 《Clinical and experimental immunology》1997,108(1):63-68
The studies presented herein examined the mechanism(s) whereby sirolimus (SRL) and cyclosporin (CsA) act synergistically to block allograft rejection. Combination index (CI=1 reflects additive, CI<1 antagonistic, and CI<1 synergistic, effects) analysis documented potent synergism between SRL and CsA to block allograft rejection. Combinations of the two drugs produced synergistic prolongation of heart (CI=0.001–0.2) or kidney (CI=0.03–0.5) allograft survival at SRL/CsA ratios ranging from 1:12.5 to 1:200. Pharmacokinetic analysis of the individual drugs showed that CsA does not affect the blood levels of SRL, and SRL mildly increases the levels of CsA in SRL/CsA-treated rats. Quantitative polymerase chain reaction analysis was used to document that both subtherapeutic (1.0 mg/kg) and therapeutic (2.0 or 4.0 mg/kg) CsA doses inhibited the expression of interferon-gamma (IFN-γ) (P<0.03) and IL-2 (P<0.003) mRNA produced by T helper (Th) 1 cells, as well as IL-10 (P<0.001), but not IL-4 (NS) mRNA produced by Th2 cells. Contrariwise, all tested SRL doses (0.02, 0.04 or 0.08 mg/kg) did not affect cytokine mRNA expression. However, heart allografts from rat recipients treated with synergistic SRL/CsA doses displayed reduced levels of IFN-γ (P<0.01), IL-2 (P<0.001) and IL-10 (P<0.001) mRNA. Thus, because subtherapeutic doses of CsA reduce Th1/Th2 activity, thereby facilitating the inhibition of signal transduction by low does of SRL, the two agents act synergistically to inhibit allograft rejection. 相似文献
6.
新免疫抑制剂雷帕霉素抗移植排斥作用的实验研究 总被引:2,自引:1,他引:2
作者研究了雷帕霉素(rapamycin;RPM)对C57BL/6J→BALB/c小鼠心肌和皮肤移植的抗移植排斥作用,结果表明 RPM比目前应用于临床器官移植的环孢菌素(Cyclosporine A;CsA)具有更好的抗移植排斥作用。此外还观察了 RPM对正在进行的移植心肌排斥反应的作用,RPM于小鼠心肌移植后第 7天开始给药与0天开始给药组相比较,移植心肌的平均存活天数无明显差异,表明RPM对心肌移植排斥反应有很好的治疗作用。小剂量的RPM与亚治疗剂量的CsA合用还有很好的协同作用。 相似文献
7.
Using a subtractlve strategy, we have cloned an activation-relatedgene from a human B cell cDNA library. Sequence analysis revealedthat this gene was identical to H12.3, a gene belonging to anexpanding family of guanlne nucleotlde-blndlng protein ßsubunlts. The expression of H12.3 was induclble in the latephase of mltogen-stlmulated T and B cells. In T cells, IL-2and IL-4 by themselves had no direct effect on the expressionof H12.3, but they could augment the level of steady-state H12.3mRNA stimulated by phytohemagglutlnln. On the other hand, IFN-and IL-6 had no obvious effect on the expression in B cellswith or without Staphytococcus aureus Cowan l-stlmulatlon. CyclosporinA, a strong immunosuppressant, Inhibited the mltogen-stlmulatedexpression of H12.3, but rapamycin, another such agent, didnot. In synchronized Jurkat cells, the expression of H12.3 hadno cell cycle-dependent decrease in S and G2/M phase, whilecyclin E, which controls the progression of the cell cycle unlate G1 phase, did show a periodic expression pattern. The resultssuggest that H12.3 might be involved in regulation of lymphocyteactivation. 相似文献
8.
Chanika Phornphutkul Ke-Ying Wu Valerie Auyeung Qian Chen Philip A Gruppuso 《Developmental dynamics》2008,237(3):702-712
The mammalian Target Of Rapamycin (mTOR) is a nutrient-sensing protein kinase that regulates numerous cellular processes. Fetal rat metatarsal explants were used as a physiological model to study the effect of mTOR inhibition on chondrogenesis. Insulin significantly enhanced their growth. Rapamycin significantly diminished this response to insulin through a selective effect on the hypertrophic zone. Cell proliferation (bromodeoxyuridine incorporation) was unaffected by rapamycin. Similar observations were made when rapamycin was injected to embryonic day (E) 19 fetal rats in situ. In the ATDC5 chondrogenic cell line, rapamycin inhibited proteoglycan accumulation and collagen X expression. Rapamycin decreased content of Indian Hedgehog (Ihh), a regulator of chondrocyte differentiation. Addition of Ihh to culture medium reversed the effect of rapamycin. We conclude that modulation of mTOR signaling contributes to chondrocyte differentiation, perhaps through its ability to regulate Ihh. Our findings support the hypothesis that nutrients, acting through mTOR, directly influence chondrocyte differentiation and long bone growth. 相似文献
9.
Burkhard Tönshoff Helio Tedesco-Silva Robert Ettenger Martin Christian Anna Bjerre Luca Dello Strologo Stephen D. Marks Lars Pape Udaykiran Veldandi Patricia Lopez Marc Cousin Priti Pandey Matthias Meier 《American journal of transplantation》2021,21(1):123-137
CRADLE was a 36-month multicenter study in pediatric (≥1 to <18 years) kidney transplant recipients randomized at 4 to 6 weeks posttransplant to receive everolimus + reduced-exposure tacrolimus (EVR + rTAC; n = 52) with corticosteroid withdrawal at 6-month posttransplant or continue mycophenolate mofetil + standard-exposure TAC (MMF + sTAC; n = 54) with corticosteroids. The incidence of composite efficacy failure (biopsy-proven acute rejection [BPAR], graft loss, or death) at month 36 was 9.8% vs 9.6% (difference: 0.2%; 80% confidence interval: −7.3 to 7.7) for EVR + rTAC and MMF + sTAC, respectively, which was driven by BPARs. Graft loss was low (2.1% vs 3.8%) with no deaths. Mean estimated glomerular filtration rate at month 36 was comparable between groups (68.1 vs 67.3 mL/min/1.73 m2). Mean changes (z-score) in height (0.72 vs 0.39; P = .158) and weight (0.61 vs 0.82; P = .453) from randomization to month 36 were comparable, whereas growth in prepubertal patients on EVR + rTAC was better (P = .050) vs MMF + sTAC. The overall incidence of adverse events (AEs) and serious AEs was comparable between groups. Rejection was the leading AE for study drug discontinuation in the EVR + rTAC group. In conclusion, though AE-related study drug discontinuation was higher, an EVR + rTAC regimen represents an alternative treatment option that enables withdrawal of steroids as well as reduction of CNIs for pediatric kidney transplant recipients. ClinicalTrials.gov: NCT01544491. 相似文献
10.