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The Implications Of Gap Junction Inhibition In Jurkat Cell-CellCommunication And ProliferationShaw, Jeremy Joseph Porter 16 May 2014 (has links)
No description available.
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An Analysis of the Effects of Pertussis Toxin on T Cell SignalingSchneider, Olivia Dawn January 2009 (has links)
No description available.
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Regulation of Calcium Entry Pathway in Jurkat T CellsFruasaha, Petronilla A. January 2008 (has links)
No description available.
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Endocrine disruption and human health : from populations to cells : an integrated approach in the study of bisphenol ACipelli, Riccardo January 2013 (has links)
Background. Endocrine disruptors (EDC) are exogenous compounds that mimic the action of natural hormones and alter the normal endocrine system. Life-long chronic exposure to Bisphenol A (BPA), a putative EDC, has been linked with risk of metabolic disorders in epidemiological studies. Objectives. The aim was to study the human health effects of exposure to BPA, using an integrated approach combining environmental epidemiology and toxicology. Methods. Urinary levels of BPA exposure were measured in participants of the InChianti longitudinal study, a representative population-based study of Italian adults, at the Baseline (1998-00) and nine years later (3rd Wave, 2007-09). Hormones levels and the gene expression of specific target genes were the end points considered. Results were validated in laboratory studies on a human leukemic T-cell line (Jurkat cells). Results. In general, urinary BPA (uBPA) concentrations were higher among men and younger respondents, and within subjects uBPA concentrations were correlated (r=0.58; p=0.013, model adjusted for age, sex, urinary creatinine). At baseline, uBPA concentration were associated with higher total testosterone concentrations in men (β = 0.05; 95% CI, 0.02–0.08). In the 3rd wave, gene expression analysis revealed positive associations between uBPA concentrations and ESR2 (estrogen receptor beta) expression (β=0.18; 95% CI: 0.04, 0.32) and ESRRA (estrogen related receptor alpha) expression (β= 0.17; 95% CI: 0.02, 0.32). In a following in vitro study, BPA exposure (0.001-1 micro molar) led to enhanced expression of ESRRA and ESR2 in Jurkat cells over a period of 72 hours. Conclusions. Results indicate that BPA is bioactive in the human body and is able to alter circulating hormone concentrations and estrogen receptor/estrogen-related receptr gene expression. In particular, given the role of ERRα as a major control point for oxidative metabolism and heart development, this research provides indications on the possible molecular mechanisms of action of BPA in metabolic diseases.
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The mechanism of T cell dysfunction induced by DiethylstilbestrolBrown, Nicole Chantae 01 January 2005 (has links)
Estrogens have the ability to alter the immune system. Diethylstilbestrol (DES), asynthetic estrogen, is known to have estrogenic activity and induce thymic alterations.We investigated the mechanism by which DES is able to alter T cells and thus theimmune system. First, we studied the effect of DES on mature T cells by using the T cellleukemia cell line, Jurkat. We found that DES treatment reduced cell viability andincreased apoptosis. Additionally, apoptosis was found to involve both death receptorand mitochondria1 pathways. Furthermore, estrogen receptor beta was found to beexpressed in these cells and increased following DES treatment. Secondly, we studiedthe effect of DES on developing T cells using two different mouse models, timed pregnant and HY-TCR transgenic. The pregnant mouse model showed that DESexposure in utero reduced thymic cell viability and induced apoptosis at gestational day(gd)-17. Apoptosis was found to involve the death receptor pathway. Additionally,alterations in T cell subsets was most pronounced at gd-17 as well. The HY-TCR tgmouse model showed that DES exposure altered both positive and negative selection of Tcells. Furthermore, DES was found to alter the ability of T cells to proliferate during animmune response. Finally, we studied the intrathymic interaction between thymicstromal cells and thymic T cells. We found that cel1:cell interaction was important forinducing T cell apoptosis in the thymus. Additionally, FasL expression was increased onthymic stromal cells following DES exposure. Furthermore, the presence of both FasL onstromal cells and Fas on T cells was important for inducing T cell apoptosis in thethymus.
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Modulation par le récepteur neurokinine-1du mécanisme d’action des immunosuppresseurs chez les cellules T.Jizi, Khadije 08 1900 (has links)
Le récepteur neurokinine 1 (NK1R) est impliqué dans la régulation des réponses immunitaires innées et adaptatives. Cependant, les mécanismes par lesquels le NK1R modulerait ces réponses ne sont pas connus. Chez les cellules T, les voies de la calcineurine et de la mTOR constituent les cibles d’immunosuppresseurs, comme la cyclosporine A (CsA), le tacrolimus et la rapamycine. Ainsi, nous avons voulu déterminer si le NK1R pourrait agir sur ces voies et si le blocage pharmacologique du NK1R avec des antagonistes sélectifs, pourrait augmenter l’action de ces immunosuppresseurs sur l’activation des cellules T. Tout d’abord, nos résultats ont montré que les cellules Jurkat (celules T humaines) exprimaient à la fois le gène du NK1R et de son ligand (les endokinines). Ceci suggère l'existence d'une régulation autocrine tachykinergique de la fonction des cellules T. Cette hypothèse est appuyée par nos données, où nous avons observé que le blocage du NK1R avec des antagonistes spécifiques (L-733,060 et L-703,606) chez les cellules Jurkat, inhibe la production d'IL-2 et diminue l'activation du NFAT (substrat de la calcineurine). De façon intéressante, nous avons montré un effet de combinaison entre les antagonistes du NK1R et les inhibiteurs de la calcineurine (CsA et tacrolimus) sur la production d’IL-2 et l’activation du NFAT. En revanche, le blocage du NK1R n'a pas d'effet inhibiteur sur l’activation de la mTOR et la p70S6K, mais réduit la phosphorylation de S6R (Ser235/236) et Akt (Ser473). Enfin, nous n’avons observé aucun effet de combinaison avec la rapamycine et l’antagoniste NK1R sur l’activation de mTOR et de sa voie de signalisation. L’ensemble de nos résultats, démontrent la présence d'un nouveau mécanisme de régulation de NFAT impliquant le système tachykinergique NK1R/endokinines chez les cellules T. Par conséquent, nous suggérons que la combinaison des antagonistes NK1R avec les inhibiteurs de la calcineurine pourrait être une alternative thérapeutique intéressante afin de réduire les doses de CsA et le FK506 dans les protocoles de prévention de rejet de greffes. / There are increasing evidences for a role of the neurokinin 1 receptor (NK1R) in the regulation of innate and adaptive immune systems. However, whether NK1R regulates calcineurin/nuclear factor of activated T cell (NFAT) and mTOR pathways in T cells is unknown. These signalling pathways being targets of the immunosuppressive drugs cyclosporine A (CsA), FK506 and rapamycin respectively. We also examined whether pharmacological blockade of NK1R may be combined to those immunosuppressors to repress T cell activation. In this article, we first show that Jurkat T cells express both genes for NK1R and its ligands endokinins which suggests the existence of an autocrine tachykinergic regulation of T cells function. This hypothesis is supported by our data showing that blockade of this receptor with specific NK1R antagonists inhibits IL-2 production in Jurkat T cells which is associated with the reduction of NFAT activation. Interestingly, we show interplay between NK1R antagonists and calcineurin inhibitors to repress IL-2 production and NFAT activation. In contrast, blockade of NK1R has no inhibitory effect on mTOR and p70S6K activation but reduce S6R (Ser235/236) and Akt (Ser473) phosphorylation. However, combining rapamycin with NK1R antagonist has no enhancing effect on rapamycin-reduced mTOR activation and its signalling pathway. Our findings provide the evidence of a novel mechanism of regulation of NFAT activation-induced IL-2 production in T cells involving the tachykinergic system NK1R/endokinins. These observations may offer new application for NK1R antagonists in transplantation immunotherapy in combination with immunosuppressors.
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Cyclic nucleotide regulated calcium signaling in vascular and jurkat T cells. / CUHK electronic theses & dissertations collectionJanuary 2011 (has links)
cAMP-elevating agents such as adenosine and epinephrine (after binding to beta-adrenergic receptor) contribute to local vascular dilation and some of these dilations are endothelium-dependent. Previous intracellular Ca 2+ imaging studies in mouse microvessel endothelial cells reported that addition of adenosine or epinephrine induced a Ca2+ influx which is blocked by CNG channel blockers such as L-cis-diltiazem or LY83583. Inside-out patch clamp studies confirmed the existence of a cAMP-activated current in endothelial cells, strongly suggesting a functional role of CNG, in particular CNGA2, channels in endothelial cells. The current study went further to show that similar Ca2+ influx in response to adenosine or epinephrine occurred in endothelial cells in freshly isolated mouse aortic strips and was again blocked by L-cis-diltiazem. By measuring the isometric force developed in mouse aortic strips, we showed that CNGA2 channel-mediated Ca2+ influx in endothelial cells contributed to the endothelium-dependent vascular dilatation in response to adenosine and epinephrine. / In conclusion, cyclic nucleotides playa vital role in the regulation of intracellular Ca2+ concentration in vascular cells and Jurket T cells. / In Jurkat T cells, cyclic nucleotides regulated Ca2+ mobilization in a different way. Fluorescence-imaging studies showed that cGMP inhibited store-operated Ca2+ influx and histamine-induced Ca 2+ rise in Jurkat T cells through activation of PKG. / Thromboxane A2 (TxA2)-induced smooth muscle contraction has been implicated in cardiovascular, renal and respiratory diseases. This contraction can partly be attributed to TxA2-induced Ca2+ influx, which activates the Ca2+-calmodulin-MLCK pathway. This study aims to identify the channels that mediate TxA2-induced Ca2+ influx in vascular smooth muscle cells. Application of U-46619, a thromboxane A2 mimic, resulted in a constriction in endothelium-denuded small mesenteric artery segments. The constriction relied on the presence of extracellular Ca2+, because removal of extracellular Ca2+ abolished the constriction. This constriction was partially inhibited by a L-type Ca2+ channel inhibitor nifedipine (0.5-1 muM). The remaining component was inhibited by L-cis-diltiazem, a selective inhibitor for CNG channels, in a dose-dependent manner, Another CNG channel blocker LY83583 [6-(phenylamino)-5,8-quinolinedione] had similar effect. In primary cultured smooth muscle cells derived from rat aorta, application of U46619 (100 nM) induced a rise in cytosolic Ca2+, which was inhibited by L-cis-diltiazem. Immunoblot experiments confirmed the presence Of CNGA2 protein in vascular smooth muscle cells, These data suggest a functional role of CNG channels in U-46619-induced Ca 2+ influx and contraction of smooth muscle cells. / Leung, Yuk Ki. / "August 2010." / Adviser: Yao Xiaoxiang. / Source: Dissertation Abstracts International, Volume: 73-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 116-132). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.
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The evaluation of the effects of semi-purified extracts of Commelina benghalensis on the molecular events associated with the growth, apoptosis and cell cycle progression of Jurkat-T cellsLebogo, Kgomotso Welheminah January 2007 (has links)
Thesis (M.Sc. (Biochemistry )) --University of Limpopo, 2007 / Refer to document / The Cannon Collins Trust Fund and the National Research Foundation
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The Effects of Crude Methanolic Extract of Commelina benghalensis Linn on the Expression of Apoptotic and Cell Division Cycle Genes in Jurkat T and Wil-2 NSCancer Cell Lines.Mbazima, Vusi G. January 2009 (has links)
Thesis (Ph.D. (Biochemistry)) --University of Limpopo, 2009 / Commelina benghalensis Linn is used in traditional medicine in several Asian
and African countries for the treatment of various ailments such as stomach
irritations, burns, sore throat and feet, diarrhoea and as an anti-inflammatory
agent. Recently, our laboratory showed that the crude methanolic extract of
Commelina benghalensis L (CMECB) exhibits growth inhibitory and proapoptotic
effects in Jurkat T and Wil-2 NS cancer cell lines. In this study, the
precise molecular mechanism(s) associated with CMECB-induced growth
inhibitory and apoptosis inducing effects in Jurkat T and Wil-2 NS cell lines
were investigated. This was achieved by investigating the effects of the
extract on the cell division cycle distribution profile as well as its effects on
various cell division cycle and apoptosis regulatory genes. Ground stems of C.
benghalensis L were extracted with absolute methanol to obtain a crude
extract. To assess the effect of CMECB on cancer cell growth, experimental
cell cultures were exposed to various concentrations (0 to 600 μg/ml) of
CMECB for up to 72 hours. The results demonstrated a significant reduction in
cell viability and inhibition of proliferation of experimental cell cultures as
determined by the trypan blue dye exclusion assay and the Coulter counter
method, respectively. Analysis of nuclear morphological changes in cells
stained with Hoechst 33258 confirmed apoptosis as the mode of cell death
that is associated with the growth inhibitory effects of CMECB in both the
Jurkat T and Wil-2 NS cell lines. This assertion was based on the observed
presence of nuclear morphological changes such as chromatin condensation
and fragmentation and apoptotic bodies in cells exposed to CMECB. In order
to get an insight on the pro-apoptotic mechanisms of CMECB, Western blot
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and quantitative real-time PCR (qrt-PCR) were used to investigate the
expression profiles of various apoptosis and cell division cycle regulatory
genes. Qrt-PCR results showed a lack of a clear up- and/or down-regulatory
effects of CMECB on the mRNA expression levels of bax and bcl-2 in both
Jurkat T and Wil-2 NS cells.
Western blot analyses demonstrated that CMECB induced apoptosis by
facilitating Bax protein translocation from the cytosol to the mitochondria in
both Jurkat T and Wil-2 NS cells. In addition, CMECB down-regulated Bcl-2
protein expression which, as a result, led to the shift in the Bax/Bcl-2 protein
ratio at certain time points and concentration in both Jurkat T and Wil-2 NS
cells. The modulation of the Bcl-2 family members led to mitochondrial
cytochrome c release into the cytosol and activation of caspases-9 and -3; this
was also confirmed by caspase activity assays and eventual degradation of
PARP. Furthermore, CMECB induced Jurkat T and Wil-2 NS cell division
cycle arrest at the G2/M phase as determined by flow cytometric analysis.
Western blot analyses of G2/M phase regulatory proteins demonstrated that
the CMECB-induced cell division cycle arrest was associated with the downregulation
of cyclin B1 and Cdc2 protein expression levels. Western blot
analyses results further revealed that the arrest of Wil-2 NS cells at the G2/M
phase was independent of p21 protein activity. However, Jurkat T cell division
cycle arrest was found to be mediated, in part, by p21. Quantitative real-time
PCR results did not show a clear trend in terms of the down- or up-regulatory
effects of the extracts on the G2/M phase regulatory genes. The CMECBinduced
apoptosis and G2/M arrest was found to occur in a p53-independent
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manner due to the lack and down-regulation of p53 protein levels in both
Jurkat T and Wil-2 NS cells, respectively. In conclusion, CMECB induces its
anticancer activity by inducing G2/M phase arrest and mitochondrial-mediated
apoptosis independent of p53 protein activity. Although the study did not
perform in vivo experiments to ascertain the efficacy of extracts of CMECB
against specific tumour types in animal models, the present findings somehow
validate the traditional use of C. benghalensis L as an anticancer agent. A
more definitive study needs to be done to ascertain this assertion. / National Research Foundation and the
University of Limpopo research office
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Modulation par le récepteur neurokinine-1du mécanisme d’action des immunosuppresseurs chez les cellules TJizi, Khadije 08 1900 (has links)
No description available.
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