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181.
182.
Nakamura T Terajewicz A Stein-Streilein J 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(4):2643-2646
The peripheral tolerance that is elicited by the anterior chamber-associated immune deviation (ACAID) protocol is characterized by impairment of Th1 responses such as delayed-type hypersensitivity. It has been proposed that suppression of Th1 responses is mediated by a deviation toward Th2 responses. Because NKT cells have a prominent role in ACAID and NKT cell-derived IL-13 is required in a tumor model of tolerance, we postulated that NKT cell-derived Th2 cytokines might have a role in ACAID. However, contrary to the tumor model, in this study we show that NKT cells from IL-13-deficient mice or IL-4/IL-13 double deficient mice were able to reconstitute the capability of J alpha18-deficient mice (lacking invariant NKT) to develop peripheral tolerance postintracameral inoculation of Ag. Also, we were able to induce peripheral tolerance directly in IL-13-deficient, IL-4/IL-13-double deficient, and STAT6-deficient mice by inoculation of Ag into their eye. We conclude that neither IL-4 nor IL-13 cytokines are required for the generation of efferent CD8+ T regulatory cells during eye-induced peripheral tolerance. We propose that Ags inoculated into the anterior chamber of the eye induce the immunoresponse to deviate from producing immune T effector cells to producing efferent T regulatory cells, rather than deviating from Th1- to Th2-type effector cells. 相似文献
183.
Seto M Miyamoto N Aikawa K Aramaki Y Kanzaki N Iizawa Y Baba M Shiraishi M 《Bioorganic & medicinal chemistry》2005,13(2):363-386
In order to develop orally active CCR5 antagonists, 1-propyl- or 1-isobutyl-1-benzazepine derivatives containing a sulfoxide moiety have been designed, synthesized, and evaluated for their biological activities. Sulfoxide compounds containing a 2-pyridyl group were first investigated, which led to discovering that the presence of a methylene group between the sulfoxide moiety and 2-pyridyl group was necessary for increased inhibitory activity in a binding assay. After further chemical modification, it was found that replacement of the pyridyl group with an imidazolyl or 1,2,4-triazolyl group enhanced activity in the binding assay and that S-sulfoxide compounds were more active than R-isomers. Particularly, compounds (S)-4r, (S)-4s, and (S)-4w exhibited highly potent CCR5 antagonistic activities (IC50=1.9, 1.7, 1.6 nM, respectively) and inhibitory effects (IC50=1.0, 2.8, 7.7 nM, respectively) in the HIV-1 envelope mediated membrane fusion assay, together with good pharmacokinetic properties in rats. In addition, we established the synthesis of (S)-4r and (S)-4w by asymmetric oxidation with titanium-(S)-(-)-1,1'-bi-2-naphthol complex. 相似文献
184.
Caffeic acid, a dietary phenol from coffee, fruits and vegetables, is an efficient antioxidant. However, little is known about its anti-oxidative mechanism in the modulation of fundamental cellular processes. In this study, we investigated whether caffeic acid regulates Rac1 GTPase activity, a partner of NADPH oxidase. Our results showed that caffeic acid decrease Rac1 protein level under basal conditions and incubation with angiotensin II (ANG II) in vascular smooth muscle cells. In a Rac-bound-to-PAK pull down assay, caffeic acid clearly inhibited Rac1 activity. We also observed that caffeic acid suppressed the generation of superoxide anion stimulated by ANG II that activates NADPH oxidase. On the other hand, co-incubation with caffei caid and cycloheximide significantly accelerated the Rac1 degradation. In addition, pretreatment with caffeic acid for 24 hours was able to prevent phosphorylation of MLC and HSP27, when cells were challenged with ANG II through the redox sensitive pathway. These results support the hypothesis that caffeic acid reduces Rac1 GTPase protein and activity level, followed by a down-regulation of NADPH oxidase activity. 相似文献
185.
Model mice for tissue-specific deletion of the manganese superoxide dismutase (MnSOD) gene 总被引:1,自引:0,他引:1
Ikegami T Suzuki Y Shimizu T Isono K Koseki H Shirasawa T 《Biochemical and biophysical research communications》2002,296(3):729-736
Manganese superoxide dismutase (MnSOD) is the enzyme that converts toxic O(2)(-) to H(2)O(2) in mitochondria. Previous reports showed that a deficiency of MnSOD in mice was neonatal lethal. Therefore, a model mouse was not available for the analysis of the pathological role of O(2)(-) injuries in adult tissues. To explore an adult-type model mouse, we designed tissue-specific MnSOD conditional knockout mice using a Cre-loxp system. First, we crossbred MnSOD flox mice with transgenic mice expressing Cre recombinase under the control of the chicken actin promoter (CAG). We confirmed that CAG MnSOD knockout mice were completely deficient in MnSOD and died as neonates, validating the use of the Cre-loxp system. Next, we generated liver-specific MnSOD-deficient mice by crossbreeding with Alb-Cre transgenic mice. MnSOD activity and protein were both significantly downregulated in the liver of liver-specific MnSOD knockout mice. However, no obvious morphological abnormality was observed in the liver when biochemical alterations such as lipid peroxidation were not detectable, suggesting a redundant or less important physiological role for MnSOD in the liver than previously thought. In the present study, we successfully generated tissue-specific MnSOD conditional knockout mice that would provide a useful tool for the analysis of various age-associated diseases such as diabetes mellitus, Parkinson's disease, stroke, and heart disease, when crossbred with tissue-specific transgenic Cre mice. 相似文献
186.
Takano S Aramaki Y Tsuchiya S 《Biochemical and biophysical research communications》2001,288(1):116-120
The purpose of this study was to determine the source of reactive oxygen species (ROS) generation and the contribution of ROS to the apoptosis of RAW264.7 cells induced by cationic liposomes. Cationic liposome-induced apoptosis was inhibited by lipoxygenase inhibitors, but not inhibitors of NADPH-oxidase, xanthine oxidase or cyclooxygenase. ROS generation induced by cationic liposomes was also inhibited by the lipoxygenase inhibitor NDGA. Furthermore, lipid peroxidation was observed following liposome treatment, but the apoptosis was not inhibited by the antioxidant alpha-tocopherol. These findings suggested that lipoxygenase is responsible for ROS generation, and ROS but not lipid peroxidation acts as a key mediator in the progress of apoptosis induced by cationic liposomes. 相似文献
187.
188.
189.
Hashizume K Tozawa K Endo M Aramaki I 《Bioscience, biotechnology, and biochemistry》2001,65(4):795-801
The final step of 2-methoxy-3-alkylpyrazine (MP) biosynthesis has been presumed to involve O-methylation of 2-hydroxy-3-alkylpyarzine (HP), although this reaction has never been demonstrated in organisms. We detected 2-hydroxy-3-isobutylpyrazine (IBHP) and 2-hydroxy-3-isopropylpyrazine (IPHP) in unripe grapes, and S-adenosyl-L-methionine-dependent O-methyltransferase (OMT) activity toward HP in crude extracts from young shoots and unripe grapes that accumulate MP at different levels. The levels of HP in the berries and stems were estimated by using 2-hydroxy-3-sec-butylpyrazine as an internal standard. The OMT activity observed in the crude extracts from young shoot and berries was extremely low, but no MP-decomposing activity was detected in the solutions. The levels of HP and OMT activity were closely related with the level of MP in the grapes. These results indicate that the predicted final step of MP biosynthesis exists in wine grapes. 相似文献
190.
Diurnal change in ornithine decarboxylase activity of rat liver 总被引:4,自引:0,他引:4
S Hayashi Y Aramaki T Noguchi 《Biochemical and biophysical research communications》1972,46(2):795-800