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《Nutrition, metabolism, and cardiovascular diseases : NMCD》2014,24(7):751-759
Background and aimPatients with systemic lupus erythematosus (SLE) have a higher prevalence of subclinical atherosclerosis and higher risk of cardiovascular (CV) events compared to the general population. The relative contribution of CV-, immune- and disease-related risk factors to accelerated atherogenesis in SLE is unclear.Methods and resultsFifty SLE patients with long-lasting disease (mean age 44 ± 10 years, 86% female) and 50 sex- and age-matched control subjects were studied. Common carotid artery intima-media thickness (CCA-IMT) was used as a surrogate marker of atherosclerosis. We evaluated traditional and immune- and disease-related factors, assessed multiple T-cell subsets by 10-parameter-eight-colour polychromatic flow cytometry and addressed the effect of pharmacological therapies on CCA-IMT. In SLE patients, among several cardiometabolic risk factors, only high-density lipoprotein levels (HDL) and their adenosine triphosphate-binding cassette transporter 1 (ABCA-1)-dependent cholesterol efflux capacity were markedly reduced (p < 0.01), whereas the CCA-IMT was significantly increased (p = 0.03) compared to controls. CCA-IMT correlated with systolic blood pressure, low-density lipoprotein (LDL) cholesterol and body mass index (BMI), but not with disease activity and duration. The activated CD4+HLA-DR+ and CCR5+ T-cell subsets were expanded in SLE patients. Patients under hydroxychloroquine (HCQ) therapy showed lower CCA-IMT (0.62 ± 0.08 vs. 0.68 ± 0.10 mm; p = 0.03) and better risk-factor profile and presented reduced circulating pro-atherogenic effector memory T-cell subsets and a parallel increased percentage of naïve T-cell subsets.ConclusionHDL represents the main metabolic parameter altered in SLE patients. The increased CCA-IMT in SLE patients may represent the net result of a process in which ‘classic’ CV risk factors give a continuous contribution, together with immunological factors (CD4+HLA-DR+ T cells) which, on the contrary, could contribute through flares of activity of various degrees over time. Patients under HCQ therapy present a modified metabolic profile, a reduced T-cell activation associated with decreased subclinical atherosclerosis. 相似文献
23.
Piotr Trzonkowski Alicja D?bska-?lizień Magdalena Jankowska Manuela Carvalho-Gaspar Gra?yna Moszkowska Natalie Mills Jolanta My?liwska 《Mechanisms of ageing and development》2010,131(2):96-217
Compromised immunity is the hallmark of ageing. Paradoxically, it may be “an ally” in facilitating acceptance of allogeneic grafts in the elderly. In this retrospective study we looked for biomarkers of immunosenescence that distinguish elderly recipients less prone to reject kidney allografts.Recruited kidney recipients aged ≥60 or <60 were designated ‘elderly’ and ‘young’, respectively. Both age-groups were divided according to the history of acute rejection. The phenotype, length of telomeres, expression of FoxP3 and proliferative responses were assessed in CD4+ and CD8+ T-cell subsets. In addition, IL6, IL10 and TGFβ were measured on the level of mRNA and serum protein.Acute-rejection-free history in elderly transplant recipients was associated with short telomeres, a decreased proportion of CD28+ T-cells associated with CMV-seropositivity and low proliferation of CD4+ T-cells. In contrast, elderly recipients who experienced acute rejection kept preserved telomere length, had a higher number of functional CD4+CD28+ cells and exhibited vigorous proliferation in vitro. These differences were not found in the young group.The major conclusion of this study is that the impaired condition of CD4+ T-cells, so-called immunosenescence, renders transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients of >60 years of age. 相似文献
24.
Joanna Jelenska Jodocus A. van Hal Jean T. Greenberg 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(29):13177-13182
Plant heat shock protein Hsp70 is the major target of HopI1, a virulence effector of pathogenic Pseudomonas syringae. Hsp70 is essential for the virulence function of HopI1. HopI1 directly binds Hsp70 through its C-terminal J domain and stimulates Hsp70 ATP hydrolysis activity in vitro. In plants, HopI1 forms large complexes in association with Hsp70 and induces and recruits cytosolic Hsp70 to chloroplasts, the site of HopI1 localization. Deletion of a central P/Q-rich repeat region disrupts HopI1 virulence but not Hsp70 interactions or association with chloroplasts. Thus, HopI1 must not only bind Hsp70 through its J domain, but likely actively affects Hsp70 activity and/or specificity. At high temperature, HopI1 is dispensable for P. syringae pathogenicity, unless excess Hsp70 is provided. A working hypothesis is that Hsp70 has a defense-promoting activity(s) that HopI1 or high temperature can subvert. Enhanced susceptibility of Hsp70-depleted plants to nonpathogenic strains of P. syringae supports a defense-promoting role for Hsp70. 相似文献
25.
B. C. A. M. Van Esch B. Schouten B. R. J. Blokhuis G. A. Hofman L. Boon J. Garssen L. M. J. Knippels L. E. M. Willemsen F. A. Redegeld 《Clinical and experimental allergy》2010,40(9):1414-1421
Background Symptoms of allergy are largely attributed to an IgE‐mediated hypersensitivity response. However, a considerable number of patients also exhibit clinical features of allergy without detectable systemic IgE. Previous work showed that Ig‐free light chains (IgLC) may act as an alternate mechanism to induce allergic responses. CD4+CD25+ T cells are crucial in the initiation and regulation of allergic responses and compromised function might affect the response to allergens. Objective To examine the contribution of CD4+CD25+ T cells and IgLC towards the whey‐allergic response. Methods Mice were sensitized orally with whey using cholera toxin as an adjuvant. CD25+ T cells were depleted in vivo using a CD25 mAb. The acute allergic skin response to whey and ex vivo colon reactivity was measured in the presence or absence of F991, a specific inhibitor of IgLC. Serum whey‐specific antibodies and IgLC in serum and mesenteric lymph node (MLN) supernatants were measured. Depletion of CD4+CD25+ T cells was confirmed in the spleen. Results Anti‐CD25 treatment strongly reduced whey‐specific antibody levels and resulted in a partial depletion of effector T cells and a major depletion of Foxp3+ regulatory T cells. Surprisingly, despite the abolished specific IgE response, the acute allergic skin response to whey was not affected. IgLC levels were enhanced in the serum and MLN supernatants of CD25‐depleted sensitized mice. F991 inhibited the acute skin response and colon hyperreactivity in anti‐CD25‐treated mice, indicating that these responses were mainly IgLC dependent. Conclusions Depletion of CD4+CD25+ T cells resulted in a switch from an IgE‐ to an IgLC‐dependent acute skin response and functional hyperresponsiveness of the colon. Our data suggest that CD25+ T cells play a crucial role in balancing cow's milk allergy between IgE and IgE‐independent responses and both mechanisms might play a role in allergic responses to the same allergen. Cite this as: B. C. A. M. van Esch, B. Schouten, B. R. J. Blokhuis, G. A. Hofman, L. Boon, J. Garssen L. M. J. Knippels, L. E. M. Willemsen and F. A. Redegeld, Clinical & Experimental Allergy, 2010 (40) 1414–1421. 相似文献
26.
嗜肺军团菌是一种可以引起军团菌肺炎和庞蒂亚克热的兼性胞内病原菌,主要侵染阿米巴原虫和人类巨噬细胞。该菌在宿主胞内能依靠Dot/Icm IVB型分泌系统产生的效应蛋白成功逃避溶酶体的降解。本文主要对嗜肺军团菌的致病物质、胞内存活与增殖机制及其效应蛋白的生物学功能进行综述,详细介绍嗜肺军团菌的毒力因子与致病机制,为军团病防治的研究提供新思路,也为其他胞内病原菌所致感染性疾病的研究提供重要的借鉴意义。 相似文献
27.
Regulation of proliferation, survival and apoptosis by members of the TNF superfamily 总被引:30,自引:0,他引:30
Tumor necrosis factor (TNF) was first identified in 1984 as a cytokine with anti-tumor effects in vitro and in vivo. Extensive research since then has shown that there are at least 18 distinct members of the TNF super family and they exhibit 15-25% amino acid sequence homology with each other. These family members bind to distinct receptors, which are homologous in their extracellular domain. These cytokines have been implicated in a wide variety of diseases including tumorigenesis, septic shock, viral replication, bone resorption, rheumatoid arthritis, diabetes, and other inflammatory diseases. TNF blockers have been approved for human use in treating some of these conditions in the United States and other countries. Various members of the TNF super family mediate either proliferation, survival, or apoptosis of cells. Although distinct receptors, all members share a common cell signaling pathway that mediates the activation of nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinases (e.g. c-jun N-terminal kinase). Regulation of cell growth and activation of NF-kappaB and of c-jun N-terminal kinase by the TNF super family is mediated through sequential activation/association of a set of cell signaling proteins named TNF receptor-associated factors, Fas-associated death domain and FADD-like ICE, caspases, receptor-interacting protein, NF-kappaB-inducing kinases, and IkappaBalpha kinases. Both apoptotic and antiapoptotic signals are activated simultaneously by the same cytokine in the same cell. Together these cytokines regulate cell growth/survival/apoptosis in a complex dance of changing partners and overlapping steps. 相似文献
28.
Costimulation of memory T-cells by ICOS: a potential therapeutic target for autoimmunity? 总被引:2,自引:0,他引:2
Approaches that target costimulatory receptors are independent of T-cell receptor specificity and may be useful for T-cell-mediated diseases in which the antigens involved are not well defined. However, the proper costimulatory pathways need to be targeted. For example, therapies for human T-cell-mediated diseases need to be effective against previously activated memory cells. In this review, we use autoimmune demyelination as a paradigm for established immune-mediated pathogenesis. Studies with the human disease multiple sclerosis and the rodent model experimental autoimmune encephalomyelitis have suggested that the effectiveness of CD28 blockade, as a therapeutic strategy for established autoimmune demyelination, may be limited. ICOS, a receptor that appears to be involved in the costimulation of previously activated T-cells, may be an attractive alternative. 相似文献
29.
OBJECTIVE: Studies have suggested that the middle ear is a potential site of immunological regulation and that the middle ear mucosa constitutes a part of the mucosal immune system. We clarify the characteristics of the middle ear mucosa with respect to immune potential. STUDY DESIGN: We investigated lymphocyte subsets, mRNA of cytokines, and induction of antigen-specific IgA-producing cells in the middle ear mucosa in specific pathogen-free C57BL/6 mice. RESULTS: Flow cytometric analysis showed a certain amount (10%-15%) of gammadelta T cells among CD3+ T cells. P6-specific IgA-producing cells were induced by intranasal immunization with P6 together with cholera toxin. RT-PCR assay of mucosal T cells detected mRNA of Th2 type cytokines such as IL-5 and IL-10. CONCLUSION: These findings support the fact that the middle ear is potentially an effector site of the mucosal immunity. 相似文献
30.
M. Yu. Klimova I. V. Bogdashin V. V. Novitskii E. D. Gol'dberg 《Bulletin of experimental biology and medicine》1990,109(1):80-82
Institute of Pharmacology, Tomsk Scientific Center, Academy of Medical Sciences of the USSR. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109. No. 1, pp. 60–62, January, 1990. 相似文献