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61.
IL-21 counteracts the regulatory T cell-mediated suppression of human CD4+ T lymphocytes 总被引:12,自引:0,他引:12
Peluso I Fantini MC Fina D Caruso R Boirivant M MacDonald TT Pallone F Monteleone G 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(2):732-739
High expression of IL-21 and/or IL-21R has been described in T cell-mediated inflammatory diseases characterized by defects of counterregulatory mechanisms. CD4(+)CD25(+) regulatory T cells (Treg) are a T cell subset involved in the control of the immune responses. A diminished ability of these cells to inhibit T cell activation has been documented in immune-inflammatory diseases, raising the possibility that inflammatory stimuli can block the regulatory properties of Treg. We therefore examined whether IL-21 controls CD4(+)CD25(+) T cell function. We demonstrate in this study that IL-21 markedly enhances the proliferation of human CD4(+)CD25(-) T cells and counteracts the suppressive activities of CD4(+)CD25(+) T cells on CD4(+)CD25(-) T cells without affecting the percentage of Foxp3(+) cells or survival of Treg. Additionally, CD4(+)CD25(+) T cells induced in the presence of IL-21 maintain the ability to suppress alloresponses. Notably, IL-21 enhances the growth of CD8(+)CD25(-) T cells but does not revert the CD4(+)CD25(+) T cell-mediated suppression of this cell type, indicating that IL-21 makes CD4(+) T cells resistant to suppression rather than inhibiting CD4(+)CD25(+) T cell activity. Finally, we show that IL-2, IL-7, and IL-15, but not IL-21, reverse the anergic phenotype of CD4(+)CD25(+) T cells. Data indicate that IL-21 renders human CD4(+)CD25(-) T cells resistant to Treg-mediated suppression and suggest a novel mechanism by which IL-21 could augment T cell-activated responses in human immune-inflammatory diseases. 相似文献
62.
63.
De Santa F Albini S Mezzaroma E Baron L Felsani A Caruso M 《Molecular and cellular biology》2007,27(20):7248-7265
The expression of retinoblastoma (pRb) and cyclin D3 proteins is highly induced during the process of skeletal myoblast differentiation. We have previously shown that cyclin D3 is nearly totally associated with hypophosphorylated pRb in differentiated myotubes, whereas Rb-/- myocytes fail to accumulate the cyclin D3 protein despite normal induction of cyclin D3 mRNA. Here we report that pRb promotes cyclin D3 protein accumulation in differentiating myoblasts by preventing cyclin D3 degradation. We show that cyclin D3 displays rapid turnover in proliferating myoblasts, which is positively regulated through glycogen synthase kinase 3beta (GSK-3beta)-mediated phosphorylation of cyclin D3 on Thr-283. We describe a novel interaction between pRb and cyclin D3 that maps to the C terminus of pRb and to a region of cyclin D3 proximal to the Thr-283 residue and provide evidence that the pRb-cyclin D3 complex formation in terminally differentiated myotubes hinders the access of GSK-3beta to cyclin D3, thus inhibiting Thr-283 phosphorylation. Interestingly, we observed that the ectopic expression of a stabilized cyclin D3 mutant in C2 myoblasts enhances muscle-specific gene expression; conversely, cyclin D3-null embryonic fibroblasts display impaired MyoD-induced myogenic differentiation. These results indicate that the pRb-dependent accumulation of cyclin D3 is functionally relevant to the process of skeletal muscle cell differentiation. 相似文献
64.
Zhang Q Zulfiqar F Xiao X Riazuddin SA Ahmad Z Caruso R MacDonald I Sieving P Riazuddin S Hejtmancik JF 《Human genetics》2007,122(3-4):293-299
Mutation in the PROM1 gene previously has been identified in one family with retinal degeneration for which neither ERG recordings
nor detailed information about visual impairment is available. A large family with multiple individuals affected by retinal
degeneration was ascertained in the Punjab province of Pakistan. The visual acuity of all affected patients in the family
was severely compromised beginning in early childhood. The retinal disease in this family is a severe form of retinitis pigmentosa
(RP) accompanied by macular degeneration. Fundus changes advanced with age. Choriocapillaris atrophy and posterior RPE atrophy
were obvious allowing visualization of the large choroidal vessels in patients over 40 years of age. Rod and cone responses
on ERG recordings were extinguished in patient’s teens. A genome-wide scan mapped the disease to a 34.7 cM region of chromosome
4p14–p16 between D4S1599 and D4S405. A maximum lod score of 3.96 with D4S403 and D4S391 is seen at θ = 0. Sequence analysis
of PROM1 located in the linkage interval identified a c.1726C>T homozygous transition in exon 15: resulting in p.Gln576X in
the translated protein. This mutation is found in a homozygous state in all six affected individuals and was heterozygous
in five of the six unaffected family members examined. The mutation was not detected in 192 chromosomes of unrelated control
individuals of the same ethnicity and from the same region. This delineates the phenotypic characteristics of retinopathy
caused by mutations in PROM1.
Qingjiong Zhang, Fareeha Zulfiqar, Xueshan Xiao, Sheikh Riazuddin and J. Fielding Hejtmancik contributed equally. 相似文献
65.
66.
Portincasa P Grattagliano I Testini M Caruso ML Wang DQ Moschetta A Calamita G Vacca M Valentini AM Renna G Lissidini G Palasciano G 《Free radical biology & medicine》2007,42(9):1381-1391
Whereas long-term cholestasis results in intestinal alterations and increased permeability to hepatotoxins, the effect of short-term cholestasis is less known and was investigated in bile duct ligated (BDL) rats. In the intestinal mucosa, at Day 7 BDL, total glutathione and protein sulfhydryl contents had decreased, oxidized glutathione levels increased (P<0.05 vs baseline), and a reduced epithelium thickness with dissolving crypt phenomena was observed in 40% of rats. At Day 10, total protein content, glutathione-related enzyme activities, and the transmural electrophysiological activity had decreased (-50%); by contrast, oxidized proteins doubled (P<0.05), and histological changes were extended to 70% of rats. In vitro exposure to taurodeoxycholate at micellar concentrations determined dysepithelization in normal gut but dissolving crypt phenomena and necrosis in cholestatic bowels. In the liver, ongoing cholestasis was associated with early oxidative changes especially in mitochondria, where protein sulfhydryls were decreased and negatively correlated with glutathione-protein mixed disulfides (r=-0.807, P<0.001). Daily oral administration of tauroursodeoxycholate, a hydrophilic bile salt, and glutathione to BDL rats improved intestinal histology, function, and redox state. In conclusion, short-term cholestasis results in distinctive functional, oxidative, and morphological changes of intestinal mucosa, determined increased vulnerability to toxic injury, and parallel hepatic oxidative damage. 相似文献
67.
68.
L. Ruth Rivkin Andrea L. Case Christina M. Caruso 《Evolution; international journal of organic evolution》2015,69(5):1232-1243
Selection is frequency dependent when an individual's fitness depends on the frequency of its phenotype. Frequency‐dependent selection should be common in gynodioecious plants, where individuals are female or hermaphroditic; if the fitness of females is limited by the availability of pollen to fertilize their ovules, then they should have higher fitness when rare than when common. To test whether the fitness of females is frequency dependent, we manipulated the sex ratio in arrays of gynodioecious Lobelia siphilitica. To test whether fitness was frequency dependent because of variation in pollen availability, we compared open‐pollinated and supplemental hand‐pollinated plants. Open‐pollinated females produced more seeds when they were rare than when they were common, as expected if fitness is negatively frequency dependent. However, hand‐pollinated females also produced more seeds when they were rare, indicating that variation in pollen availability was not the cause of frequency‐dependent fitness. Instead, fitness was frequency dependent because both hand‐ and open‐pollinated females opened more flowers when they were rare than when they were common. This plasticity in the rate of anthesis could cause fitness to be frequency dependent even when reproduction is not pollen limited, and thus expand the conditions under which frequency‐dependent selection operates in gynodioecious species. 相似文献
69.
70.
Scapagnini G Vasto S Sonya V Abraham NG Nader AG Caruso C Calogero C Zella D Fabio G 《Molecular neurobiology》2011,44(2):192-201
In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies,
for the beneficial effects of some phenolic substances, contained in commonly used spices and herbs, in preventing various
age-related pathologic conditions, ranging from cancer to neurodegenerative diseases. Although the exact mechanisms by which
polyphenols promote these effects remain to be elucidated, several reports have shown their ability to stimulate a general
xenobiotic response in the target cells, activating multiple defense genes. Data from our and other laboratories have previously
demonstrated that curcumin, the yellow pigment of curry, strongly induces heme-oxygenase-1 (HO-1) expression and activity
in different brain cells via the activation of heterodimers of NF-E2-related factors 2 (Nrf2)/antioxidant responsive element (ARE) pathway. Many studies clearly demonstrate that activation ofNrf2 target genes,
and particularly HO-1, in astrocytes and neurons is strongly protective against inflammation, oxidative damage, and cell death.
In the central nervous system, the HO system has been reported to be very active, and its modulation seems to play a crucial
role in the pathogenesis of neurodegenerative disorders. Recent and unpublished data from our group revealed that low concentrations
of epigallocatechin-3-gallate, the major green tea catechin, induces HO-1 by ARE/Nrf2 pathway in hippocampal neurons, and
by this induction, it is able to protect neurons against different models of oxidative damages. Furthermore, we have demonstrated
that other phenolics, such as caffeic acid phenethyl ester and ethyl ferulate, are also able to protect neurons via HO-1 induction.
These studies identify a novel class of compounds that could be used for therapeutic purposes as preventive agents against
cognitive decline. 相似文献