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Similar Inhibition (similar + inhibition)
Selected AbstractsCD4+CD25+ regulatory T cells suppress contact hypersensitivity reactions by blocking influx of effector T cells into inflamed tissueEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2006Sabine Ring Dr. Abstract CD4+CD25+ regulatory T cells (Treg) exert suppressive functions on effector T cells in vitro and in vivo. However, the exact cellular events that mediate this inhibitory action remain largely unclear. To elucidate these events, we used intravital microscopy in a model of contact hypersensitivity (CHS) and visualized the leukocyte-endothelium interaction at the site of antigen challenge in awake C57BL/6 mice. Injection of Treg i.v. into sensitized mice at the time of local hapten challenge significantly inhibited rolling and adhesion of endogenous leukocytes to the endothelium. A similar inhibition of leukocyte recruitment could be recorded after injection of Treg-derived tissue culture supernatant. Thus, these data indicate that soluble factors may account for the suppressive effects. Accordingly we found that IL-10, but not TGF-,, was produced by Treg upon stimulation and that addition of anti-IL-10 antibodies abrogated the suppressive effects of Treg and tissue culture supernatant in CHS reactions. Moreover, CD4+CD25+ T cells isolated from IL-10,/, mice were not able to suppress the immune response induced by hapten treatment in C57BL/6 mice. In conclusion, our data suggest that cytokine-dependent rather than cell-cell contact-dependent mechanisms play a pivotal role in the suppression of CHS reactions by Treg in vivo. [source] Role of the GLT-1 subtype of glutamate transporter in glutamate homeostasis: the GLT-1-preferring inhibitor WAY-855 produces marginal neurotoxicity in the rat hippocampusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2005Julie V. Selkirk Abstract Glutamate is the major excitatory neurotransmitter in the central nervous system and is tightly regulated by cell surface transporters to avoid increases in concentration and associated neurotoxicity. Selective blockers of glutamate transporter subtypes are sparse and so knock-out animals and antisense techniques have been used to study their specific roles. Here we used WAY-855, a GLT-1-preferring blocker, to assess the role of GLT-1 in rat hippocampus. GLT-1 was the most abundant transporter in the hippocampus at the mRNA level. According to [3H]- l -glutamate uptake data, GLT-1 was responsible for approximately 80% of the GLAST-, GLT-1-, and EAAC1-mediated uptake that occurs within dissociated hippocampal tissue, yet when this transporter was preferentially blocked for 120 h with WAY-855 (100 µm), no significant neurotoxicity was observed in hippocampal slices. This is in stark contrast to results obtained with TBOA, a broad-spectrum transport blocker, which, at concentrations that caused a similar inhibition of glutamate uptake (10 and 30 µm), caused substantial neuronal death when exposed to the slices for 24 h or longer. Likewise, WAY-855, did not significantly exacerbate neurotoxicity associated with simulated ischemia, whereas TBOA did. Finally, intrahippocampal microinjection of WAY-855 (200 and 300 nmol) in vivo resulted in marginal damage compared with TBOA (20 and 200 nmol), which killed the majority of both CA1,4 pyramidal cells and dentate gyrus granule cells. These results indicate that selective inhibition of GLT-1 is insufficient to provoke glutamate build-up, leading to NMDA receptor-mediated neurotoxic effects, and suggest a prominent role of GLAST and/or EAAC1 in extracellular glutamate maintenance. [source] Evidence for functional compartmentalization of trigeminal muscle spindle afferents during fictive mastication in the rabbitEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2000K. -G. Abstract Primary afferent neurons innervating muscle spindles in jaw-closing muscles have cell bodies in the trigeminal mesencephalic nucleus (NVmes) that are electrically coupled and receive synapses. Each stem axon gives rise to a peripheral branch and a descending central branch. It was previously shown that some spikes generated by constant muscle stretch fail to enter the soma during fictive mastication. The present study examines whether the central axon is similarly controlled. These axons were functionally identified in anaesthetized and paralysed rabbits, and tonic afferent firing was elicited by muscle stretch. For the purpose of comparison, responses were recorded extracellularly both from the somatic region and from the central axon in the lateral brainstem. Two types of fictive masticatory movement patterns were induced by repetitive stimulation of the masticatory cortex and monitored from the trigeminal motor nucleus. Field potentials generated by spike-triggered averaging of action potentials from the spindle afferents were employed to determine their postsynaptic effects on jaw-closing motoneurons. Tonic firing of 32% NVmes units was inhibited during the jaw-opening phase, but spike frequency during closing was almost equal to the control rate during both types of fictive mastication. A similar inhibition occurred during opening in 83% of the units recorded along the central branch. However, firing frequency in these was significantly increased during closing in 94%, probably because of the addition of antidromic action potentials generated by presynaptic depolarization of terminals of the central branch. These additional spikes do not reach the soma, but do appear to excite motoneurons. The data also show that the duration and/or frequency of firing during the bursts varied from one pattern of fictive mastication to another. We conclude that the central axons of trigeminal muscle spindle afferents are functionally decoupled from their stem axons during the jaw-closing phase of mastication. During this phase, it appears that antidromic impulses in the central axons provide one of the inputs from the masticatory central pattern generator (CPG) to trigeminal motoneurons. [source] Functional demonstration of surface carbonic anhydrase IV activity on rat astrocytesGLIA, Issue 3 2006Nataliya Svichar Abstract Buffering of the brain extracellular fluid is catalyzed by carbonic anhydrase (CA) activity. Whereas the extracellular isoform CA XIV has been localized exclusively to neurons in the brain, and to glial cells in the retina, there has been uncertainty regarding the form or forms of CA on the surface of brain astrocytes. We addressed this issue using physiological methods on cultured and acutely dissociated rat astrocytes. Prior work showed that the intracellular lactate-induced acidification (LIA) of astrocytes is diminished by benzolamide, a poorly permeant, nonspecific CA inhibitor. We demonstrate that pretreatment of astrocytes with phosphatidylinositol-specific phospholipase C (PI-PLC) results in a similar inhibition of the mean LIA (by 66 ± 3%), suggesting that the glycosylphosphatidylinositol-anchored CA IV was responsible. Pretreatment of astrocytes with CA IV inhibitory antisera also markedly reduced the mean LIA in both cultured cortical (by 46 ± 4%) and acutely dissociated hippocampal astrocytes (by 54 ± 8%). Pre-immune sera had no effect. The inhibition produced by PIPLC or CA IV antisera was not significantly less than that by benzolamide, suggesting that the majority of detectable surface CA activity was attributable to CA IV. Thus, our data collectively document the presence of CAIV on the surface of brain astrocytes, and suggest that this is the predominant CA isoform on these cells. © 2005 Wiley-Liss, Inc. [source] Correlation between beta-lipoprotein levels and outcome of hepatitis C treatment,HEPATOLOGY, Issue 2 2006Kavitha Gopal The low-density lipoprotein receptor (LDLR) has been proposed as a candidate receptor for the hepatitis C virus (HCV). Competitive inhibition of HCV binding to the LDLR by low-density lipoprotein (LDL) has been shown in vitro. If similar inhibition occurs in vivo, an elevated serum concentration of beta- lipoproteins may reduce the efficiency of infecting hepatocytes with HCV by competitively inhibiting HCV viral receptor binding. We investigated the role of baseline lipid values in influencing the outcome of HCV treatment. We conducted a retrospective chart review of patients treated with an interferon-based regimen at our liver and gastroenterology clinics between 1998 and 2004. Of 99 patients enrolled in the study, 49 (49.5%) had HCV genotype 1 (LDL 100.2 ± 30.2 mg/dL [mean ± SD]), and 50 patients (50.5%) had genotype 2 or 3 (LDL 110.1 ± 40 mg/dL) infection. Early viral response (EVR), end-of-treatment response (ETR), and sustained viral response (SVR) were documented in 99, 88, and 77 patients, respectively. LDL and cholesterol levels prior to treatment were found to be higher in patients with positive EVR, ETR, and SVR. This difference remained significant independent of age. Multivariate analysis controlling for genotype and age showed that the higher the cholesterol and LDL levels prior to treatment, the greater the odds of responding to treatment. In conclusion, having higher serum LDL and cholesterol levels before treatment may be significant prognostic indicators for treatment outcome of those with chronic hepatitis C infection, particularly in genotypes 1 and 2. (HEPATOLOGY 2006;44:335,340.) [source] Effects of date extract on adhesion of Candida species to human buccal epithelial cells in vitroJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 5 2000Khaled H. Abu-Elteen Abstract: The adherence of three Candida species to human buccal epithelial cells (BEC) following treatment with different concentrations of date extract was investigated in vitro, as well as the effect of a mouth rinse with date extract on the adhesion of yeast to BEC. Adhesion of C.albicans, C.tropicalis and C.kefyr to BEC was significantly reduced after both short- and long-term periods of yeast exposure to various concentrations of date extract (reduction between 25% and 52% of the control value). A similar inhibition of adherence was observed upon pre-incubation of BEC with date extract. There was a significant reduction (P<0.001) in the adherence of yeast to BEC collected immediately or 5,20 min after an oral rinse with 10% date extract. No statistically significant difference was observed in the adhesion of BEC collected 30 min after an oral rinse with date extract and control BEC. In addition, pre-treatment of either Candida or BEC, or both, with date extract resulted in reduced adherence, the magnitude of which was largest when both types of cells were pre-treated. Date extract also inhibited germ-tube formation of C. albicans (56,85% inhibition), which might contribute to the effects on adherence. [source] Effect of pretreatment with piperonyl butoxide on pyrethroid efficacy against insecticide-resistant Helicoverpa armigera (Lepidoptera: Noctuidae) and Bemisia tabaci (Sternorrhyncha: Aleyrodidae)PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 2 2006Susan J Young Abstract Pyrethroid resistance in B-type Bemisia tabaci Gennadius and Australian Helicoverpa armigera Hübner field populations is primarily conferred by esterase isoenzymes which metabolise and sequester pyrethroid insecticides. It has been shown previously that pyrethroid resistance-associated esterases in H. armigera are inhibited by the insecticide synergist piperonyl butoxide (PBO) over a 22-h period. It is demonstrated here that similar inhibition can be obtained against B-type B. tabaci. Small-scale field trials showed excellent levels of pyrethroid control when insects were pretreated with PBO and then dosed with pyrethroid during the time of maximum esterase inhibition. These results demonstrate that PBO can restore pyrethroid efficacy in the field against both B-type B. tabaci and resistant H. armigera. Copyright © 2005 Society of Chemical Industry [source] 19 Cytosolic phospholipase A2 increases proliferation, inhibits apoptosis and facilitates angiogenesis in prostate cancer: a potential new therapeutic targetBJU INTERNATIONAL, Issue 2006M.I. PATEL The end-products from the arachadonic acid (AA) pathway have been shown to be tumourigenic in prostate cancer (CaP). Cytosolic phospholipase A2 (cPLA2) is the enzyme that liberates AA from plasma membranes and feeds it to the cycloxygenase and lipoxygenase pathways. In this study we aim to determine the importance of cPLA2 in prostate cancer by examining human prostate cancer specimens and in vitro cell line models. Immunohistochemistry of human prostate specimens revealed that activated cPLA2 levels were significantly higher in prostate cancer compared to benign glands.. Next to determine if inhibition of cPLA2 would lead to decreases in prostate cancer growth, we treated three CaPcell lines (PC3, DU145 and LNCaP) with pyrrolidine 2 (P2), a specific cPLA2 inhibitor and showed it significantly inhibited the growth of all three cell lines at concentrations between 1,10,M by MTS assay. P2 treatment induced a cell cycle block at G0/G1 and a corresponding reduction in BrdU incoprporation by flow cytometry and 3H-Thymidine incorporation. In addition cPLA2 knock by siRNA also showed a similar inhibition in proliferation, confirming the importance of cPLA2 in CaP proliferation. P2 also induced apoptosis in CaP cell lines by Caspase 3/7 assay. Treatment of Endothelial cell (HUVECs) cells with P2 had a very significant inhibitory effect on capillary tube formation in matrigel. We conclude that cytosolic phospholipase A2 is overactive in human prostate cancer. It leads to CaP proliferation as well as apoptosis. cPLA2 also is required in endothelial angiogenesis. Inhitibion of cPLA2 by P2 will reduce cancer growth, induce apoptosis and inhibit angiogeneisis in an in vitro model. Together, these findings suggest that cPLA2 could be a potential target in CaP treatment and warrants further validation in animal and human trials. [source] | |||||||||||||