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1.
Déborah Ancel Arnaud Bernard Selvakumar Subramaniam Akira Hirasawa Gozoh Tsujimoto Toshihiro Hashimoto Patricia Passilly-Degrace Naim-Akhtar Khan Philippe Besnard 《Journal of lipid research》2015,56(2):369-378
Implication of the long-chain fatty acid (LCFA) receptor GPR120, also termed free fatty acid receptor 4, in the taste-guided preference for lipids is a matter of debate. To further unravel the role of GPR120 in the “taste of fat”, the present study was conducted on GPR120-null mice and their wild-type littermates. Using a combination of morphological [i.e., immunohistochemical staining of circumvallate papillae (CVP)], behavioral (i.e., two-bottle preference tests, licking tests and conditioned taste aversion) and functional studies [i.e., calcium imaging in freshly isolated taste bud cells (TBCs)], we show that absence of GPR120 in the oral cavity was not associated with changes in i) gross anatomy of CVP, ii) LCFA-mediated increases in intracellular calcium levels ([Ca2+]i), iii) preference for oily and LCFA solutions and iv) conditioned avoidance of LCFA solutions. In contrast, the rise in [Ca2+]i triggered by grifolic acid, a specific GPR120 agonist, was dramatically curtailed when the GPR120 gene was lacking. Taken together, these data demonstrate that activation of lingual GPR120 and preference for fat are not connected, suggesting that GPR120 expressed in TBCs is not absolutely required for oral fat detection in mice 相似文献
2.
Duftner C Dejaco C Hengster P Bijuklic K Joannidis M Margreiter R Schirmer M 《PloS one》2012,7(3):e33939
Background
Pro-inflammatory, cytotoxic CD4+CD28− T-cells with known defects in apoptosis have been investigated as markers of premature immuno-senescence in various immune-mediated diseases. In this study we evaluated the influence of polyclonal antilymphocyte globulins (ATG-Fresenius, ATG-F) on CD4+CD28− T-cells in vivo and in vitro.Principal Findings
Surface and intracellular three colour fluorescence activated cell sorting analyses of peripheral blood mononuclear cells from 16 consecutive transplant recipients and short-term cell lines were performed. In vivo, peripheral levels of CD3+CD4+CD28− T-cells decreased from 3.7±7.1% before to 0±0% six hours after ATG-F application (P = 0.043) in 5 ATG-F treated but not in 11 control patients (2.9±2.9% vs. 3.9±3.0%). In vitro, ATG-F induced apoptosis even in CD4+CD28− T-cells, which was 4.3-times higher than in CD4+CD28+ T-cells. ATG-F evoked apoptosis was partially reversed by the broad-spectrum caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk) and prednisolon-21-hydrogensuccinate. ATG-F triggered CD25 expression and production of pro-inflammatory cytokines, and induced down-regulation of the type 1 chemokine receptors CXCR-3, CCR-5, CX3CR-1 and the central memory adhesion molecule CD62L predominately in CD4+CD28− T-cells.Conclusion
In summary, in vivo depletion of peripheral CD3+CD4+CD28− T-cells by ATG-F in transplant recipients was paralleled in vitro by ATG-F induced apoptosis. CD25 expression and chemokine receptor down-regulation in CD4+CD28− T-cells only partly explain the underlying mechanism. 相似文献3.
Background
Accurate, inexpensive point-of-care CD4+ T cell testing technologies are needed that can deliver CD4+ T cell results at lower level health centers or community outreach voluntary counseling and testing. We sought to evaluate a point-of-care CD4+ T cell counter, the Pima CD4 Test System, a portable, battery-operated bench-top instrument that is designed to use finger stick blood samples suitable for field use in conjunction with rapid HIV testing.Methods
Duplicate measurements were performed on both capillary and venous samples using Pima CD4 analyzers, compared to the BD FACSCalibur (reference method). The mean bias was estimated by paired Student''s t-test. Bland Altman plots were used to assess agreement.Results
206 participants were enrolled with a median CD4 count of 396 (range; 18–1500). The finger stick PIMA had a mean bias of −66.3 cells/µL (95%CI −83.4−49.2, P<0.001) compared to the FACSCalibur; the bias was smaller at lower CD4 counts (0–250 cells/µL) with a mean bias of −10.8 (95%CI −27.3−+5.6, P = 0.198), and much greater at higher CD4 cell counts (>500 cells/µL) with a mean bias of −120.6 (95%CI −162.8, −78.4, P<0.001). The sensitivity (95%CI) of the Pima CD4 analyzer was 96.3% (79.1–99.8%) for a <250 cells/ul cut-off with a negative predictive value of 99.2% (95.1–99.9%).Conclusions
The Pima CD4 finger stick test is an easy-to-use, portable, relatively fast device to test CD4+ T cell counts in the field. Issues of negatively-biased CD4 cell counts especially at higher absolute numbers will limit its utility for longitudinal immunologic response to ART. The high sensitivity and negative predictive value of the test makes it an attractive option for field use to identify patients eligible for ART, thus potentially reducing delays in linkage to care and ART initiation. 相似文献4.
Background
Aberrant CD40 ligand (CD154) expression occurs on both T cells and B cells in human lupus patients, which is suggested to enhance B cell CD40 signaling and play a role in disease pathogenesis. Transgenic mice expressing CD154 by their B cells (CD154TG) have an expanded spleen B cell pool and produce autoantibodies (autoAbs). CD22 deficient (CD22−/−) mice also produce autoAbs, and importantly, their B cells are hyper-proliferative following CD40 stimulation ex vivo. Combining these 2 genetic alterations in CD154TGCD22−/− mice was thereby predicted to intensify CD40 signaling and autoimmune disease due to autoreactive B cell expansion and/or activation.Methodology/Principal Findings
CD154TGCD22−/− mice were assessed for their humoral immune responses and for changes in their endogenous lymphocyte subsets. Remarkably, CD154TGCD22−/− mice were not autoimmune, but instead generated minimal IgG responses against both self and foreign antigens. This paucity in IgG isotype switching occurred despite an expanded spleen B cell pool, higher serum IgM levels, and augmented ex vivo B cell proliferation. Impaired IgG responses in CD154TGCD22−/− mice were explained by a 16-fold expansion of functional, mature IL-10-competent regulatory spleen B cells (B10 cells: 26.7×106±6 in CD154TGCD22−/− mice; 1.7×106±0.4 in wild type mice, p<0.01), and an 11-fold expansion of B10 cells combined with their ex vivo-matured progenitors (B10+B10pro cells: 66×106±3 in CD154TGCD22−/− mice; 6.1×106±2 in wild type mice, p<0.01) that represented 39% of all spleen B cells.Conclusions/Significance
These results demonstrate for the first time that the IL-10-producing B10 B cell subset has the capacity to suppress IgG humoral immune responses against both foreign and self antigens. Thereby, therapeutic agents that drive regulatory B10 cell expansion in vivo may inhibit pathogenic IgG autoAb production in humans. 相似文献5.
Sasson SC Zaunders JJ Seddiki N Bailey M McBride K Koelsch KK Merlin KM Smith DE Cooper DA Kelleher AD 《PloS one》2012,7(2):e31148
Aim
HIV infection is associated with distortion of T-cell homeostasis and the IL-7/IL7R axis. Progressive infection results in loss of CD127+132− and gains in CD127−132+ CD4+ and CD8+ T-cells. We investigated the correlates of loss of CD127 from the T-cell surface to understand mechanisms underlying this homeostatic dysregulation.Methods
Peripheral and cord blood mononuclear cells (PBMCs; CBMC) from healthy volunteers and PBMC from patients with HIV infection were studied. CD127+132−, CD127+132+ and CD127−132+ T-cells were phenotyped by activation, differentiation, proliferation and survival markers. Cellular HIV-DNA content and signal-joint T-cell receptor excision circles (sjTRECs) were measured.Results
CD127+132− T-cells were enriched for naïve cells while CD127−132+ T-cells were enriched for activated/terminally differentiated T-cells in CD4+ and CD8+ subsets in health and HIV infection. HIV was associated with increased proportions of activated/terminally differentiated CD127−132+ T-cells. In contrast to CD127+132− T-cells, CD127−132+ T-cells were Ki-67+Bcl-2low and contained increased levels of HIV-DNA. Naïve CD127+132− T-cells contained a higher proportion of sjTRECs.Conclusion
The loss of CD127 from the T-cell surface in HIV infection is driven by activation of CD127+132− recent thymic emigrants into CD127−132+ activated/terminally differentiated cells. This process likely results in an irreversible loss of CD127 and permanent distortion of T-cell homeostasis. 相似文献6.
JD Coso C González-Millán JJ Salinero J Abián-Vicén L Soriano S Garde B Pérez-González 《PloS one》2012,7(8):e43280
Background
To investigate the cause/s of muscle fatigue experienced during a half-iron distance triathlon.Methodology/Principal Findings
We recruited 25 trained triathletes (36±7 yr; 75.1±9.8 kg) for the study. Before and just after the race, jump height and leg muscle power output were measured during a countermovement jump on a force platform to determine leg muscle fatigue. Body weight, handgrip maximal force and blood and urine samples were also obtained before and after the race. Blood myoglobin and creatine kinase concentrations were determined as markers of muscle damage.Results
Jump height (from 30.3±5.0 to 23.4±6.4 cm; P<0.05) and leg power output (from 25.6±2.9 to 20.7±4.6 W · kg−1; P<0.05) were significantly reduced after the race. However, handgrip maximal force was unaffected by the race (430±59 to 430±62 N). Mean dehydration after the race was 2.3±1.2% with high inter-individual variability in the responses. Blood myoglobin and creatine kinase concentration increased to 516±248 µg · L−1 and 442±204 U · L−1, respectively (P<0.05) after the race. Pre- to post-race jump change did not correlate with dehydration (r = 0.16; P>0.05) but significantly correlated with myoglobin concentration (r = 0.65; P<0.001) and creatine kinase concentration (r = 0.54; P<0.001).Conclusions/significance
During a half-iron distance triathlon, the capacity of leg muscles to produce force was notably diminished while arm muscle force output remained unaffected. Leg muscle fatigue was correlated with blood markers of muscle damage suggesting that muscle breakdown is one of the most relevant sources of muscle fatigue during a triathlon. 相似文献7.
Bieghs V Verheyen F van Gorp PJ Hendrikx T Wouters K Lütjohann D Gijbels MJ Febbraio M Binder CJ Hofker MH Shiri-Sverdlov R 《PloS one》2012,7(3):e34378
Background & Aims
Non-alcoholic steatohepatitis (NASH) is characterized by steatosis and inflammation, which can further progress into fibrosis and cirrhosis. Recently, we demonstrated that combined deletion of the two main scavenger receptors, CD36 and macrophage scavenger receptor 1 (MSR1), which are important for modified cholesterol-rich lipoprotein uptake, reduced NASH. The individual contributions of these receptors to NASH and the intracellular mechanisms by which they contribute to inflammation have not been established. We hypothesize that CD36 and MSR1 contribute independently to the onset of inflammation in NASH, by affecting intracellular cholesterol distribution inside Kupffer cells (KCs).Methods & Results
Ldlr−/− mice were transplanted with wild-type (Wt), Cd36−/− or Msr1−/− bone marrow and fed a Western diet for 3months. Cd36−/−- and Msr1−/−- transplanted (tp) mice showed a similar reduction in hepatic inflammation compared to Wt-tp mice. While the total amount of cholesterol inside KCs was similar in all groups, KCs of Cd36−/−- and Msr1−/−-tp mice showed increased cytoplasmic cholesterol accumulation, while Wt-tp mice showed increased lysosomal cholesterol accumulation.Conclusion
CD36 and MSR1 contribute similarly and independently to the progression of inflammation in NASH. One possible explanation for the inflammatory response related to expression of these receptors could be abnormal cholesterol trafficking in KCs. These data provide a new basis for prevention and treatment of NASH. 相似文献8.
CD44s and CD44v6 expression in head and neck epithelia 总被引:1,自引:0,他引:1
Background
CD44 splice variants are long-known as being associated with cell transformation. Recently, the standard form of CD44 (CD44s) was shown to be part of the signature of cancer stem cells (CSCs) in colon, breast, and in head and neck squamous cell carcinomas (HNSCC). This is somewhat in contradiction to previous reports on the expression of CD44s in HNSCC. The aim of the present study was to clarify the actual pattern of CD44 expression in head and neck epithelia.Methods
Expression of CD44s and CD44v6 was analysed by immunohistochemistry with specific antibodies in primary head and neck tissues. Scoring of all specimens followed a two-parameters system, which implemented percentages of positive cells and staining intensities from − to +++ (score = %×intensity; resulting max. score 300). In addition, cell surface expression of CD44s and CD44v6 was assessed in lymphocytes and HNSCC.Results
In normal epithelia CD44s and CD44v6 were expressed in 60–95% and 50–80% of cells and yielded mean scores with a standard error of a mean (SEM) of 249.5±14.5 and 198±11.13, respectively. In oral leukoplakia and in moderately differentiated carcinomas CD44s and CD44v6 levels were slightly increased (278.9±7.16 and 242±11.7; 291.8±5.88 and 287.3±6.88). Carcinomas in situ displayed unchanged levels of both proteins whereas poorly differentiated carcinomas consistently expressed diminished CD44s and CD44v6 levels. Lymphocytes and HNSCC lines strongly expressed CD44s but not CD44v6.Conclusion
CD44s and CD44v6 expression does not distinguish normal from benign or malignant epithelia of the head and neck. CD44s and CD44v6 were abundantly present in the great majority of cells in head and neck tissues, including carcinomas. Hence, the value of CD44s as a marker for the definition of a small subset of cells (i.e. less than 10%) representing head and neck cancer stem cells may need revision. 相似文献9.
Background and Aims
In neotropical forests, very small-seeded pioneer species (<0·1 mg seed mass) recruit preferentially in small tree fall gaps and at gap edges, but large-seeded pioneers do not. Since water availability is related to gap size, these differences in microsite preference may reflect in part species-specific differences in germination at reduced water potentials.Methods
For 14 neotropical pioneer species, the hypothesis is tested that small-seeded species, with shallow initial rooting depths, reduce the risks associated with desiccation by germinating more slowly and at higher water potentials than large-seeded species.Key Results
Germination occurred both more quickly and at lower water potentials with increasing seed mass. For example, Ochroma pyramidale (seed mass 5·5 mg) had a time to 50 % germination (T50) of 2·8 d and a median base potential for germination (ψb50) of −1·8 MPa while Clidemia quinquenervia (seed mass 0·017 mg) had a T50 of 17·6 d and ψb50 of −1·1 MPa.Conclusions
These data suggest that small-seeded species germinate only in comparatively moist microsites, such as small canopy gaps, which may reduce the risk of drought-induced mortality. Conversely, large-seeded species are able to germinate in the drier environment of large gaps, where they benefit by enhanced seedling growth in a high irradiance environment. The positive association of seed size and canopy gap size for optimal seedling establishment is maintained by differential germination responses to soil water availability coupled with the scaling of radicle growth rate and seed size, which collectively confer greater drought tolerance on large-seeded species.Key words: Germination, seed size, Panamá, neotropical, pioneer, water potential 相似文献10.
Purpose
To investigate the mechanisms underpinning modifications in glucose homeostasis and insulin sensitivity 24 h after a bout of resistance exercise (RE) with or without protein ingestion.Methods
Twenty-four healthy males were assigned to a control (CON; n = 8), exercise (EX; n = 8) or exercise plus protein condition (EX+PRO; n = 8). Muscle biopsy and blood samples were obtained at rest for all groups and immediately post-RE (75% 1RM, 8×10 repetitions of leg-press and extension exercise) for EX and EX+PRO only. At 24 h post-RE (or post-resting biopsy for CON), a further muscle biopsy was obtained. Participants then consumed an oral glucose load (OGTT) containing 2 g of [U-13C] glucose during an infusion of 6, 6-[2H2] glucose. Blood samples were obtained every 10 min for 2 h to determine glucose kinetics. EX+PRO ingested an additional 25 g of intact whey protein with the OGTT. A final biopsy sample was obtained at the end of the OGTT.Results
Fasted plasma glucose and insulin were similar for all groups and were not different immediately post- and 24 h post-RE. Following RE, muscle glycogen was 26±8 and 19±6% lower in EX and EX+PRO, respectively. During OGTT, plasma glucose AUC was lower for EX and EX+PRO (75.1±2.7 and 75.3±2.8 mmol·L−1∶120 min, respectively) compared with CON (90.6±4.1 mmol·L−1∶120 min). Plasma insulin response was 13±2 and 21±4% lower for EX and CON, respectively, compared with EX+PRO. Glucose disappearance from the circulation was ∼12% greater in EX and EX+PRO compared with CON. Basal 24 h post-RE and insulin-stimulated PAS-AS160/TBC1D4 phosphorylation was greater for EX and EX+PRO.Conclusions
Prior RE improves glycemic control and insulin sensitivity through an increase in the rate at which glucose is disposed from the circulation. However, co-ingesting protein during a high-glucose load does not augment this response at 24 h post-exercise in healthy, insulin-sensitive individuals. 相似文献11.
Background and Aims
Floral thermogenesis occurs in at least 12 families of ancient seed plants. Some species show very high rates of respiration through the alternative pathway, and some are thermoregulatory, with increasing respiration at decreasing ambient temperature. This study assesses the intensity and regulation of respiration in three species of African Hydnora that represent the Hydnoraceae, an unusual family of holoparasitic plants from arid environments.Methods
Long-term respirometry (CO2 production) and thermometry were carried out on intact flowers of H. africana, H. abyssinica and H. esculenta in the field, and short-term measurements were made on floral parts during the protogynous flowering sequence.Key Results
For H. africana, there was no temperature elevation in either the osmophores or the gynoecial chamber in any phase, and mass-specific respiration rates of the flower parts were low (maximum 8·3 nmol CO2 g−1 s−1 in osmophore tissue). Respiration tracked ambient and floral temperatures, eliminating the possibility of the inverse relationship expected in thermoregulatory flowers. Hydnora abyssinica flowers had higher respiration (maximum 27·5 nmol g−1 s−1 in the osmophores) and a slight elevation of osmophore temperature (maximum 2·8 °C) in the female stage. Respiration by gynoecial tissue was similar to that of osmophores in both species, but there was no measurable elevation of gynoecial chamber temperature. Gynoecial chamber temperature of H. esculenta could reach 3·8 °C above ambient, but there are no respiration data available. Antheral tissue respiration was maximal in the male phase (4·8 nmol g−1 s−1 in H. africana and 10·3 nmol g−1 s−1 in H. abyssinica), but it did not raise the antheral ring temperature, which showed that thermogenesis is not a by-product of pollen maturation or release.Conclusions
The exceptionally low thermogenesis in Hydnora appears to be associated with scent production and possibly gynoecial development, but has little direct benefit to beetle pollinators.Key words: Pollination biology, Hydnora, thermogenesis, respiration rate, temperature, flowers, insects 相似文献12.
Background
Few data have been published on the associations of ferritin with trunk and leg fat depots. We aimed to investigate these associations in a Chinese population.Methodology
Trunk fat mass and leg fat mass were determined in a cross-sectional sample of 1,150 Chinese (479 men and 671 women) aged 50–70 years by dual-energy X-ray absorptiometry scan. Fasting plasma ferritin was measured.Principal Findings
Plasma ferritin was positively correlated with waist circumference, waist-to-hip ratio, total body fat and trunk fat mass, but inversely correlated with leg fat mass in men (r = 0.16, 0.26, 0.19, 0.22 and −0.12, respectively, all P<0.05) and women (r = 0.16, 0.16, 0.08, 0.17 and −0.12, respectively, all P<0.05). Multivariate regression analysis showed that ferritin levels increased with larger trunk fat mass (β = 0.33 ± 0.08 for men and β = 0.21 ± 0.05 for women, both P<0.001) while decreased with larger leg fat mass (β = −0.12 ± 0.09, P = 0.15 for men; and β = −0.14 ± 0.05, P = 0.005 for women). Moreover, plasma ferritin levels decreased with increasing tertile of leg fat mass among each tertile of trunk fat mass.Conclusion
This is the first study to report the opposite associations of trunk and leg fat depots with plasma ferritin levels. 相似文献13.
de Vries HS te Morsche RH van Oijen MG Nagtegaal ID Peters WH de Jong DJ 《PloS one》2010,5(11):e15011
Background
Cyclooxygenase-2 (COX-2) is a key enzyme involved in the conversion of arachidonic acid into prostaglandins. COX-2 is mainly induced at sites of inflammation in response to proinflammatory cytokines such as interleukin-1α/β, interferon-γ and tumor necrosis factor-α produced by inflammatory cells.Aim
The aim of this study was to investigate the possible modulating effect of the functional COX-2 polymorphisms −1195 A→G and −765G→C on the risk for development of inflammatory bowel disease (IBD) in a Dutch population.Methods
Genomic DNA of 525 patients with Crohn''s disease (CD), 211 patients with ulcerative colitis (UC) and 973 healthy controls was genotyped for the −1195 A→G (rs689466) and −765G→C (rs20417) polymorphisms. Distribution of genotypes in patients and controls were compared and genotype-phenotype interactions were investigated.Results
The genotype distribution of the −1195A→G polymorphism was not different between the patients with CD or UC and the control group. The −765GG genotype was more prevalent in CD patients compared to controls with an OR of 1.33 (95%CI 1.04–1.69, p<0.05). The −765GC and −765CC genotype carriers showed a tendency to be less frequent in patients with CD compared to controls, with ORs of 0.78 (95%CI: 0.61–1.00) and 0.49 (95%CI 0.22–1.08), respectively. Combining homozygous and heterozygous patients with the −765C allele showed a reduced risk for developing CD, with an OR of 0.75 (95%CI: 0.59–0.96). In the context of this, the G−1195G−765/A−1195C−765 diplotype was significantly less common in patients with CD compared to controls, with an OR of 0.62 (95%CI: 0.39–0.98). For UC however, such an effect was not observed. No correlation was found between COX-2 diplotypes and clinical characteristics of IBD.Conclusions
The −765G→C polymorphism was associated with a reduced risk for developing Crohn''s disease in a Dutch population. 相似文献14.
Sharp ER Willberg CB Kuebler PJ Abadi J Fennelly GJ Dobroszycki J Wiznia AA Rosenberg MG Nixon DF 《PloS one》2012,7(1):e29154
Background
In the USA, most HIV-1 infected children are on antiretroviral drug regimens, with many individuals surviving through adolescence and into adulthood. The course of HIV-1 infection in these children is variable, and understudied.Methodology/Principal Findings
We determined whether qualitative differences in immune cell subsets could explain a slower disease course in long term survivors with no evidence of immune suppression (LTS-NS; CD4%≥25%) compared to those with severe immune suppression (LTS-SS; CD4%≤15%). Subjects in the LTS-NS group had significantly higher frequencies of naïve (CCR7+CD45RA+) and central memory (CCR7+CD45RA−) CD4+ T cells compared to LTS-SS subjects (p = 0.0005 and <0.0001, respectively). Subjects in the rapid progressing group had significantly higher levels of CD4+ TEMRA (CCR7−CD45RA+) cells compared to slow progressing subjects (p<0.0001).Conclusions/Significance
Rapid disease progression in vertical infection is associated with significantly higher levels of CD4+ TEMRA (CCR7−CD45RA+) cells. 相似文献15.
Background
Disturbed peripheral negative regulation might contribute to evolution of autoimmune insulitis in type 1 diabetes. This study evaluates the sensitivity of naïve/effector (Teff) and regulatory T cells (Treg) to activation-induced cell death mediated by Fas cross-linking in NOD and wild-type mice.Principal Findings
Both effector (CD25−, FoxP3−) and suppressor (CD25+, FoxP3+) CD4+ T cells are negatively regulated by Fas cross-linking in mixed splenocyte populations of NOD, wild type mice and FoxP3-GFP tranegenes. Proliferation rates and sensitivity to Fas cross-linking are dissociated in Treg cells: fast cycling induced by IL-2 and CD3/CD28 stimulation improve Treg resistance to Fas-ligand (FasL) in both strains. The effector and suppressor CD4+ subsets display balanced sensitivity to negative regulation under baseline conditions, IL-2 and CD3/CD28 stimulation, indicating that stimulation does not perturb immune homeostasis in NOD mice. Effective autocrine apoptosis of diabetogenic cells was evident from delayed onset and reduced incidence of adoptive disease transfer into NOD.SCID by CD4+CD25− T cells decorated with FasL protein. Treg resistant to Fas-mediated apoptosis retain suppressive activity in vitro. The only detectable differential response was reduced Teff proliferation and upregulation of CD25 following CD3-activation in NOD mice.Conclusion
These data document negative regulation of effector and suppressor cells by Fas cross-linking and dissociation between sensitivity to apoptosis and proliferation in stimulated Treg. There is no evidence that perturbed AICD in NOD mice initiates or promotes autoimmune insulitis. 相似文献16.
Background
Nitric oxide (NO) plays an important role in mobilization of endothelial progenitor cells (EPCs). We hypothesized that inhaled NO (iNO) would induce EPC mobilization and therefore promote lung repair in acute respiratory distress syndrome (ARDS).Methodology/Principal Findings
Healthy piglets were randomized into four groups (n = 6): Control (Con; mechanical ventilation only); ARDS (established by oleic acid infusion and mechanical ventilation); ARDS plus granulocyte-colony stimulating factor (G-CSF; 10 µg/kg/d subcutaneously); ARDS plus NO inhalation (iNO; 10 ppm). EPCs and mobilizing cytokines were assayed at different time points (baseline, 0, 24, 72 and 168 h) and injury reparation was assessed at 168 h. Compared to the Con group, the levels of EPCs were increased in bone marrow but not in blood in the ARDS group at 24 h. Compared to the ARDS group, inhaled NO induced a rapid elevation in the number of CD34+KDR+, KDR+CD133+ and CD34+KDR+CD133+ EPCs in blood (2163±454 vs. 1094±416, 1302±413 vs. 429±244, 1140±494 vs. 453±273 cells/ml, respectively, P<0.05), and a reduction in the percentage of KDR+CD133+ cells in bone marrow. Lung CD34, CD133, VEGF, VEGF receptor 2, endothelial NO synthase mRNA, and VEGF and VEGF receptor 2 protein expression levels were augmented in the iNO group, but not in the G-CSF group, compared to ARDS. Furthermore, iNO treatment reduced vascular permeability, increased pulmonary vessel density, and alleviated pulmonary edema and inflammation compared to ARDS treatment. Plasma VEGF, stromal cell-derived factor-1 (SDF-1) and bone marrow NO2 −/NO3 − were significantly higher in the iNO group compared to the ARDS group at 72 h.Conclusions
These results suggest that iNO induces mobilization of EPCs from bone marrow into circulation, contributes to vascular repair, and thereby alleviates lung damage. 相似文献17.
S. Brunel B. Teulat-Merah M.-H. Wagner T. Huguet J. M. Prosperi C. D��rr 《Annals of botany》2009,103(7):1103-1117
Background and Aims
The framework provided by an emergence model was used: (1) for phenotyping germination and heterotrophic growth of Medicago truncatula in relation to two major environmental factors, temperature and water potential; and (2) to evaluate the extent of genetic differences in emergence-model parameters.Methods
Eight cultivars and natural accessions of M. trunculata were studied. Germination was recorded from 5 to 30 °C and from 0 to −0·75 MPa, and seedling growth from 10 to 20 °C.Key Results
Thermal time to reach 50 % germination was very short (15 °Cd) and almost stable between genotypes, while base temperature (2–3 °C) and base water potential for germination (−0·7 to −1·3 MPa) varied between genotypes. Only 35 °Cd after germination were required to reach 30 mm hypocotyl length with significant differences among genotypes. Base temperature for elongation varied from 5·5 to 7·5 °C. Low temperatures induced a general shortening of the seedling, with some genotypes more responsive than others. No relationship with initial seed mass or seed reserve distribution was observed, which might have explained differences between genotypes and the effects of low temperatures.Conclusions
The study provides a set of reference values for M. trunculata users. The use of the ecophysiological model allows comparison of these values between such non-crop species and other crops. It has enabled phenotypic variability in response to environmental conditions related to the emergence process to be identified. The model will allow simulation of emergence differences between genotypes in a range of environments using these parameter values. Genomic tools available for the model species M. trunculata will make it possible to analyse the genetic and molecular determinants of these differences.Key words: Core collection, emergence, Medicago truncatula, modelling, seed, temperature, water potential 相似文献18.
Wolf D Jehle F Ortiz Rodriguez A Dufner B Hoppe N Colberg C Lozhkin A Bassler N Rupprecht B Wiedemann A Hilgendorf I Stachon P Willecke F Febbraio M von zur Muhlen C Binder CJ Bode C Zirlik A Peter K 《PloS one》2012,7(3):e33026
Background
Adipose tissue inflammation fuels the metabolic syndrome. We recently reported that CD40L – an established marker and mediator of cardiovascular disease – induces inflammatory cytokine production in adipose cells in vitro. Here, we tested the hypothesis that CD40L deficiency modulates adipose tissue inflammation in vivo.Methodology/Principal Findings
WT or CD40L−/− mice consumed a high fat diet (HFD) for 20 weeks. Inflammatory cell recruitment was impaired in mice lacking CD40L as shown by a decrease of adipose tissue macrophages, B-cells, and an increase in protective T-regulatory cells. Mechanistically, CD40L-deficient mice expressed significantly lower levels of the pro-inflammatory chemokine MCP-1 both, locally in adipose tissue and systemically in plasma. Moreover, levels of pro-inflammatory IgG-antibodies against oxidized lipids were reduced in CD40L−/− mice. Also, circulating low-density lipoproteins and insulin levels were lower in CD40L−/− mice. However, CD40L−/− mice consuming HFD were not protected from the onset of diet-induced obesity (DIO), insulin resistance, and hepatic steatosis, suggesting that CD40L selectively limits the inflammatory features of diet-induced obesity rather than its metabolic phenotype. Interestingly, CD40L−/− mice consuming a low fat diet (LFD) showed both, a favorable inflammatory and metabolic phenotype characterized by diminished weight gain, improved insulin tolerance, and attenuated plasma adipokine levels.Conclusion
We present the novel finding that CD40L deficiency limits adipose tissue inflammation in vivo. These findings identify CD40L as a potential mediator at the interface of cardiovascular and metabolic disease. 相似文献19.
Background
In the intestine, the integrin CD103 is expressed on a subset of T regulatory (Treg) cells and a population of dendritic cells (DCs) that produce retinoic acid and promote immune homeostasis. However, the role of CD103 during intestinal helminth infection has not been tested.Methodology/Principal Findings
We demonstrate that CD103 is dispensable for the development of protective immunity to the helminth parasite Trichuris muris. While we observed an increase in the frequency of CD103+ DCs in the lamina propria (LP) following acute high-dose infection with Trichuris, lack of CD103 had no effect on the frequency of CD11c+ DCs in the LP or mesenteric lymph nodes (mLN). CD103-deficient (CD103−/−) mice develop a slightly increased and earlier T cell response but resolve infection with similar kinetics to control mice. Similarly, low-dose chronic infection of CD103−/− mice with Trichuris resulted in no significant difference in immunity or parasite burden. Absence of CD103 also had no effect on the frequency of CD4+CD25+Foxp3+ Treg cells in the mLN or LP.Conclusions/Significance
These results suggest that CD103 is dispensable for intestinal immunity during helminth infection. Furthermore, lack of CD103 had no effect on DC or Treg recruitment or retention within the large intestine. 相似文献20.
Del Coso J Muñoz-Fernández VE Muñoz G Fernández-Elías VE Ortega JF Hamouti N Barbero JC Muñoz-Guerra J 《PloS one》2012,7(2):e31380