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1.
We wanted to assess whether B-cell and/or T-cell responses to collagen and thereby the course of collagen-induced arthritis
could be suppressed by regulatory mechanisms associated with oral tolerance to an unrelated protein. DBA/1 mice were fed ovalbumin
(OVA)-containing pellets ad libitum for 1 week and subsequently coimmunized twice, with a mixture of bovine collagen type
II (BCII) and OVA in Freund's complete adjuvant. Mice fed OVA before coimmunization with BCII and OVA had significantly lower
arthritic scores than mice immunized with BCII only. Their body weight increased during the study period and their anti-BCII
antibody activity was significantly IgG2a lower. The frequency of spleen cells producing IgG anti-BCII antibody was also reduced. Coimmunization per se slightly ameliorated
the development of arthritis, resulting in an early, transient reduction. It resulted in significantly higher IgG1 anti-BCII antibody activity and increased splenocyte secretion of IFN-γ and IL-10 in response to BCII. Our findings demonstrate
that OVA-specific regulatory events induced by feeding OVA, i.e. bystander suppression, reduced the severity of arthritis
in animals immunized with BCII and OVA. Anti-BCII specific antibody responses and cytokine secretion by types 1 and 2 T helper
cells were also decreased. 相似文献
2.
Peeters RP Friesema EC Docter R Hennemann G Visser TJ 《American journal of physiology. Endocrinology and metabolism》2002,283(6):E1232-E1238
Liver uptake of thyroxine (T4) is mediated by transporters and is rate limiting for hepatic 3,3',5-triiodothyronine (T3) production. We investigated whether hepatic mRNA for T4 transporters is regulated by thyroid state using Xenopus laevis oocytes as an expression system. Because X. laevis oocytes show high endogenous uptake of T4, T4 sulfamate (T4NS) was used as an alternative ligand for the hepatic T4 transporters. Oocytes were injected with 23 ng liver mRNA from euthyroid, hypothyroid, or hyperthyroid rats, and after 3-4 days uptake was determined by incubation of injected and uninjected oocytes for 1 h at 25 degrees C or for 4 h at 18 degrees C with 10 nM [125I]T4NS. Expression of type I deiodinase (D1), which is regulated by thyroid state, was studied in the oocytes as an internal control. Uptake of T4NS showed similar approximately fourfold increases after injection of liver mRNA from euthyroid, hypothyroid, or hyperthyroid rats. A similar lack of effect of thyroid state was observed using reverse T3 as ligand. In contrast, D1 activity induced by liver mRNA from hyperthyroid and hypothyroid rats in the oocytes was 2.4-fold higher and 2.7-fold lower, respectively, compared with euthyroid rats. Studies have shown that uptake of iodothyronines in rat liver is mediated in part by several organic anion transporters, such as the Na+/taurocholate-cotransporting polypeptide (rNTCP) and the Na-independent organic anion-transporting polypeptide (rOATP1). Therefore, the effects of thyroid state on rNTCP, rOATP1, and D1 mRNA levels in rat liver were also determined. Northern analysis showed no differences in rNTCP or rOATP1 mRNA levels between hyperthyroid and hypothyroid rats, whereas D1 mRNA levels varied widely as expected. These results suggest little effect of thyroid state on the levels of mRNA coding for T4 transporters in rat liver, including rNTCP and rOATP1. However, they do not exclude regulation of hepatic T4 transporters by thyroid hormone at the translational and posttranslational level. 相似文献
3.
B30.2-like domain proteins: update and new insights into a rapidly expanding family of proteins 总被引:5,自引:0,他引:5
Henry J; Mather IH; McDermott MF; Pontarotti P 《Molecular biology and evolution》1998,15(12):1696-1705
The B30.2 domain is a conserved region of around 170 amino acids associated
with several different protein domains, including the immunoglobulin folds
of butyrophilin and the RING finger domain of ret finger protein. We
recently reported several novel members of this family as well as
previously undescribed protein families possessing the B30.2 domain. Many
proteins have subsequently been found to possess this domain, including
pyrin/marenostrin and the midline 1 (MID1) protein. Mutations in the B30.2
domain of pyrin/marenostrin are implicated in familial Mediterranean fever,
and partial loss of the B30.2 domain of MID1 is responsible for Opitz G/BBB
syndrome, characterized by developmental midline defects. In this study, we
scrutinized the available sequence data bases for the identification of
novel B30.2 domain proteins using highly sensitive database-searching
tools. In addition, we discuss the chromosomal localization of genes in the
B30.2 family, since the encoded proteins are likely to be involved in other
forms of periodic fever, autoimmune, and genetic diseases.
相似文献
4.
Zhu J Yu M Friesema J Huang T Roman RJ Lombard JH 《American journal of physiology. Heart and circulatory physiology》2005,288(2):H908-H913
Recent studies have demonstrated that cerebral arteries from rats fed a high-salt (HS) diet exhibit impaired vasodilation and altered electrophysiological response to reduction in PO2. The present study examined whether an increase in salt intake alters the response of vascular smooth muscle cells (VSMC) to prostacyclin, a crucial mediator of hypoxic dilation in cerebral arteries. VSMC were isolated from cerebral arteries of male Sprague-Dawley rats maintained on an HS (4% NaCl) or a low-salt diet (0.4% NaCl) for 3 days. The stable prostacyclin analog iloprost (10 ng/ml) inhibited serotonin (0.1-10 microM)-induced contractions and the increase in intracellular Ca2+ concentration ([Ca2+]i) in VSMC isolated from arteries of animals fed the low-salt diet. In contrast, iloprost had no effect on serotonin-induced contractions and increases in [Ca2+]i in VSMC isolated from arteries of rats fed the HS diet. Preventing the fall in ANG in rats fed the HS diet by infusion of a low dose of ANG II (5 ng.kg(-1).min(-1) i.v.) restored the inhibitory effect of iloprost on serotonin-induced contractions and increases in [Ca2+]i in VSMC from animals fed the HS diet. These effects were reversed by AT1 receptor blockade with losartan. These results indicate that ANG II suppression secondary to elevated dietary salt intake impairs vascular relaxation and Ca2+ regulation by prostacyclin. 相似文献
5.
Zhu J Drenjancevic-Peric I McEwen S Friesema J Schulta D Yu M Roman RJ Lombard JH 《American journal of physiology. Heart and circulatory physiology》2006,291(2):H929-H938
Male Sprague-Dawley rats were maintained on a low-salt (LS) diet (0.4% NaCl) or changed to a high-salt (HS) diet (4% NaCl) for 3 days. Increases in intracellular Ca2+ ([Ca2+]i) in response to methacholine (10 microM) and histamine (10 microM) were significantly attenuated in aortic endothelial cells from rats fed a HS diet, whereas thapsigargin (10 microM)-induced increases in [Ca2+]i were unaffected. Methacholine-induced nitric oxide (NO) production was eliminated in endothelial cells of aortas from rats fed a HS diet. Low-dose ANG II infusion (5 ng x kg(-1) x min(-1) iv) for 3 days prevented impaired [Ca2+]i signaling response to methacholine and histamine and restored methacholine-induced NO production in aortas from rats on a HS diet. Adding Tempol (500 microM) to the tissue bath to scavenge superoxide anions increased NO release and caused N(omega)-nitro-L-arginine methyl ester-sensitive vascular relaxation in aortas from rats fed a HS diet but had no effect on methacholine-induced Ca2+ responses. Chronic treatment with Tempol (1 mM) in the drinking water restored NO release, augmented vessel relaxation, and increased methacholine-induced Ca2+ responses significantly in aortas from rats on a HS diet but not in aortas from rats on a LS diet. These findings suggest that 1) agonist-induced Ca2+ responses and NO levels are reduced in aortas of rats on a HS diet; 2) increased vascular superoxide levels contribute to NO destruction, and, eventually, to impaired Ca2+ signaling in the vascular endothelial cells; and 3) reduced circulating ANG II levels during elevated dietary salt lead to elevated superoxide levels, impaired endothelial Ca2+ signaling, and reduced NO production in the endothelium. 相似文献
6.
Effective cellular uptake and efflux of thyroid hormone by human monocarboxylate transporter 10 总被引:1,自引:0,他引:1
Friesema EC Jansen J Jachtenberg JW Visser WE Kester MH Visser TJ 《Molecular endocrinology (Baltimore, Md.)》2008,22(6):1357-1369
Cellular entry of thyroid hormone is mediated by plasma membrane transporters, among others a T-type (aromatic) amino acid transporter. Monocarboxylate transporter 10 (MCT10) has been reported to transport aromatic amino acids but not iodothyronines. Within the MCT family, MCT10 is most homologous to MCT8, which is a very important iodothyronine transporter but does not transport amino acids. In view of this paradox, we decided to reinvestigate the possible transport of thyroid hormone by human (h) MCT10 in comparison with hMCT8. Transfection of COS1 cells with hMCT10 cDNA resulted in 1) the production of an approximately 55 kDa protein located to the plasma membrane as shown by immunoblotting and confocal microscopy, 2) a strong increase in the affinity labeling of intracellular type I deiodinase by N-bromoacetyl-[(125)I]T(3), 3) a marked stimulation of cellular T(4) and, particularly, T(3) uptake, 4) a significant inhibition of T(3) uptake by phenylalanine, tyrosine, and tryptophan of 12.5%, 22.2%, and 51.4%, respectively, and 5) a marked increase in the intracellular deiodination of T(4) and T(3) by different deiodinases. Cotransfection studies using the cytosolic thyroid hormone-binding protein micro-crystallin (CRYM) indicated that hMCT10 facilitates both cellular uptake and efflux of T(4) and T(3). In the absence of CRYM, hMCT10 and hMCT8 increased T(3) uptake after 5 min incubation up to 4.0- and 1.9-fold, and in the presence of CRYM up to 6.9- and 5.8-fold, respectively. hMCT10 was less active toward T(4) than hMCT8. These findings establish that hMCT10 is at least as active a thyroid hormone transporter as hMCT8, and that both transporters facilitate iodothyronine uptake as well as efflux. 相似文献
7.
The potent enediyne antitumor antibiotic C1027 has been previously reported to induce novel DNA interstrand cross-links and drug monoadducts under anaerobic conditions [Xu et al. (1997) J. Am. Chem. Soc. 119, 1133-1134]. In the present study, we explored the mechanism of formation of these anaerobic DNA lesions. We found that, similar to the aerobic reaction, the diradical species of the activated drug initiates anaerobic DNA damage by abstracting hydrogen atoms from the C4', C1', and C5' positions of the A1, A2, and A3 nucleotides, respectively, in the most preferred 5'GTTA1T/5'ATA2A3C binding sequence. It is proposed that the newly generated deoxyribosyl radicals, which cannot undergo oxidation, likely add back onto the nearby unsaturated ring system of the postactivated enediyne core, inducing the formation of interstrand cross-links, connecting either A1 to A2 or A1 to A3, or drug monoadducts mainly on A2 or A3. Comparative studies with other enediynes, such as neocarzinostatin and calicheamicin gamma1I under similar reaction conditions indicate that the anaerobic reaction process is a kinetically competitive one, depending on the proximity of the drug unsaturated ring system or dioxygen to the sugar radicals and their quenching by other hydrogen sources such as solvent or thiols. It was found that C1027 mainly generates interstrand cross-links, whereas most of the anaerobic lesions produced by neocarzinostatin are drug monoadducts. Calicheamicin gamma1I was found to be less efficient in producing both lesions. The anaerobic DNA lesions induced by enediyne antitumor antibiotics may have important implications for their potent cytotoxicity in the central regions of large tumors, where relative anaerobic conditions prevail. 相似文献
8.
9.
Nelson?DuránEmail author Priscyla?D?Marcato Oswaldo?L?Alves Gabriel?IH?De Souza Elisa?Esposito 《Journal of nanobiotechnology》2005,3(1):8
Extracellular production of metal nanoparticles by several strains of the fungus Fusarium oxysporum was carried out. It was found that aqueous silver ions when exposed to several Fusarium oxysporum strains are reduced in solution, thereby leading to the formation of silver hydrosol. The silver nanoparticles were in the
range of 20–50 nm in dimensions. The reduction of the metal ions occurs by a nitrate-dependent reductase and a shuttle quinone
extracellular process. The potentialities of this nanotechnological design based in fugal biosynthesis of nanoparticles for
several technical applications are important, including their high potential as antibacterial material. 相似文献
10.
Elisabeth G. W. Huijskens Johan Reimerink Paul G. H. Mulder Janko van Beek Adam Meijer Erwin de Bruin Ingrid Friesema Menno D. de Jong Guus F. Rimmelzwaan Marcel F. Peeters John W. A. Rossen Marion Koopmans 《PloS one》2013,8(1)