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Selected AbstractsIL-15 is critical for the maintenance and innate functions of self-specific CD8+ T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2009Momoe Itsumi Abstract IL-15 is a pleiotropic cytokine involved in host defense as well as autoimmunity. IL-15-deficient mice show a decrease of memory phenotype (MP) CD8+ T cells, which develop naturally in naïve mice and whose origin is unclear. It has been shown that self-specific CD8+ T cells developed in male H-Y antigen-specific TCR transgenic mice share many similarities with naturally occurring MP CD8+ T cells in normal mice. In this study, we found that H-Y antigen-specific CD8+ T cells in male but not female mice decreased when they were crossed with IL-15-deficient mice, mainly due to impaired peripheral maintenance. The self-specific TCR transgenic CD8+ T cells developed in IL-15-deficient mice showed altered surface phenotypes and reduced effector functions ex vivo. Bystander activation of the self-specific CD8+ T cells was induced in vivo during infection with Listeria monocytogenes, in which proliferation but not IFN-, production was IL-15-dependent. These results indicated important roles for IL-15 in the maintenance and functions of self-specific CD8+ T cells, which may be included in the naturally occurring MP CD8+ T-cell population in naïve normal mice and participate in innate host defense responses. [source] Modulatory effects of curcumin and resveratrol on lung carcinogenesis in micePHYTOTHERAPY RESEARCH, Issue 9 2010Anshoo Malhotra Abstract The aim of the present study is to explore the chemopreventive potential of curcumin and resveratrol during promotional phase of benzo(a)pyrene (BP) induced lung carcinogenesis in mice. The mice were segregated into five groups which included normal control, BP-treated, BP+curcumin-treated, BP+resveratrol-treated and BP+curcumin+resveratrol-treated groups. The BP treatment resulted in a significant increase in the levels of lipid peroxidation (LPO). On the other hand, reduced glutathione (GSH) levels and the activities of superoxide dismutase (SOD) were found to be significantly decreased following BP treatment. Administration of curcumin to BP-treated mice decreased the levels of LPO significantly. Further, treatment of resveratrol to BP-treated mice significantly elevated the activities of SOD. Combined treatment of curcumin and resveratrol, kowever, showed significant improvement in LPO and GSH levels as well as in the activities of SOD. Histo-architectural studies showed well-differentiated signs of lung carcinogenesis following BP administration to mice. Although treatments with resveratrol and curcumin given separately to BP-treated mice showed appreciable improvement in the histo-architecture of the lung, combined treatment resulted in a noticeable improvement in the lung histo-architecture. Copyright © 2009 John Wiley & Sons, Ltd. [source] Preventive Effects of Quercetin against Benzo[a]pyrene-Induced DNA Damages and Pulmonary Precancerous Pathologic Changes in MiceBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2006Nian-zu Jin In this study, mice in quercetin-treated groups were given quercetin for 90 days. After one week of treatment, mice in the quercetin-treated groups and the positive control group received a single intraperitoneal dose of benzo[a]pyrene (100 mg/kg body weight). The results of single cell gel electrophoresis assay showed that the average lengths of the comet cell tail and DNA damage in the peripheral blood lymphocytes of mice induced by benzo[a]pyrene decreased significantly as a result of quercetin treatment dose-dependently. Light microscopic examination showed that the degrees of pulmonary precancerous pathologic changes in the quercetin-treated groups decreased significantly compared with those in the positive control group. Meanwhile, the cytochrome P4501A1-linked 7-ethoxyresorufin O-dealkylase activities in lung microsomes of mice decreased as the dose of quercetin increased. The results of this in vivo study revealed that quercetin had a significant preventive effect on benzo[a]pyrene-induced DNA damage, and had a potential chemopreventive effect on the carcinogenesis of lung cancer induced by benzo[a]pyrene. The mechanism of these effects of quercetin could be related to the inhibition of cytochrome P4501A1 activity. [source] G,q -PROTEIN CARBOXYL TERMINUS IMITATION POLYPEPTIDE GCIP-27 ATTENUATES CARDIAC HYPERTROPHY IN VITRO AND IN VIVOCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2007Hai-Gang Zhang SUMMARY 1Various Gq -protein-coupled receptors, such as ,1 -adrenoceptors, angiotension AT1 receptors, endothelin ETA receptors, neuropeptide Y1 receptors etc., contribute to cardiac hypertrophy. In G-protein signalling pathways, the carboxyl terminus of the G, subunit plays a vital role within G-protein,receptor interaction. The present study was designed to explore the effects of the synthetic G,q carboxyl terminal imitation peptide GCIP-27 on cardiac hypertrophy. 2Hypertrophy of rat cultured cardiomyocytes was induced by noradrenaline (NA) or angiotensin (Ang) II in vitro. Protein content, [3H] incorporation and [Ca2+]i were determined in cardiomyocytes cultured with GCIP-27. Three in vivo animal models of cardiac hypertrophy were prepared using intraperitoneal injections of NA in mice and rats and suprarenal abdominal aortic stenosis in rats. After treatment with GCIP-27 (10,100 µg/L) for 15 or 20 days, indices of cardiac hypertrophy were measured. The effect of GCIP-27 on the mRNA expression of c-fos and c-jun was detected using reverse transcription,polymerase chain reaction. 3At 10,100 µg/L, GCIP-27 significantly decreased protein content and [3H]-leucine incorporation in cultured cardiomyocytes compared with 1 µmol/L NA- and 1 µmol/L AngII-treated groups. After treatment with GCIP-27 (10, 30 or 100 µg/kg) for 15 days, the heart index (HI) and left ventricular index (LVI) in mice decreased significantly compared with the NA control group. In rats, GCIP-27 significantly reduced HI and LVI compared with the NA and aortic stenosis groups. Moreover, [Ca2+]i in cardiomyocytes in the GCIP-27 (3, 10, 30 µg/L)-treated groups was lower than that in the control groups. Expression of c-fos and c-jun mRNA decreased significantly in the myocardium from 5,45 µg/L GCIP-27-treated rats compared with NA controls. 4The results indicate that GCIP-27 can attenuate cardiac hypertrophy effectively in various models in vitro and in vivo. [source] |