Store operated calcium entry (SOCE) downstream of T cell receptor (TCR) activation in T lymphocytes has been shown to be mediated mainly through the Calcium Release Activated Calcium (CRAC) channel. Here, we compared the effects of a novel, potent and selective CRAC inhibitor, 2,6-Difluoro-N-{5-[4-methyl-1-(5-methyl-thiazol-2-yl)-1,2,5,6-tetrahydro-pyridin-3-yl]-pyrazin-2-yl}-benzamide (RO2959), on T cell effector functions with that of a previously reported CRAC channel inhibitor, YM-58483, and a calcineurin inhibitor Cyclosporin A (CsA). Using both electrophysiological and calcium-based fluorescence measurements, we showed that RO2959 is a potent SOCE inhibitor that blocked an IP3-dependent current in CRAC-expressing RBL-2H3 cells and CHO cells stably expressing human Orai1 and Stim1, as well as SOCE in human primary CD4+ T cells triggered by either TCR stimulation or thapsigargin treatment. Furthermore, we demonstrated that RO2959 completely inhibited cytokine production as well as T cell proliferation mediated by TCR stimulation or MLR (Mixed Lymphocyte Reaction). Lastly, we showed by gene expression array analysis that RO2959 potently blocked TCR triggered gene expression and T cell functional pathways similar to CsA and FK506. Thus, both from a functional and transcriptional level, our data provide evidence that RO2959 is a novel and selective CRAC inhibitor that potently inhibits human T cell functions.
Characterization of a novel CRAC inhibitor that potently blocks human T cell activation and effector functions.
Specimen part, Treatment, Subject
View SamplesMicroRNAs are small non-coding RNA species, some of which are playing important roles in cell differentiation. However, the level of participations of microRNAs in epithelial cell differentiation is largely unknown. Here, we found that expression levels of four microRNAs (miR-210, miR-338-3p, miR-33a and miR-451) were significantly increased in differentiated stage of T84 cells, compared with undifferentiated stage. Additionally, we demonstrate that miR-338-3p and miR-451 contribute to the formation of epithelial basolateral polarity by facilitating translocalization of beta1 integrin to the basolateral membrane. However, candidate target mRNAs of miR-338-3p and miR-451 and the mechanism behind observed phenomena is uncertain. Then, we performed comprehensive gene expression analysis to identify candidate target mRNAs and understand their mechanisms.
MicroRNA-338-3p and microRNA-451 contribute to the formation of basolateral polarity in epithelial cells.
Cell line, Treatment, Time
View SamplesTankyrase enhances beta-catenin signaling via PARsylation and subsequent degradation of Axin, a negative regulator of beta-catenin. Tankyrase inhibitors stabilize Axin and suppress beta-catenin signaling. We developed a novel tankyrase inhibitor, RK-287107.
RK-287107, a potent and specific tankyrase inhibitor, blocks colorectal cancer cell growth in a preclinical model.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Heme ameliorates dextran sodium sulfate-induced colitis through providing intestinal macrophages with noninflammatory profiles.
Specimen part, Treatment
View SamplesIn murine large intestinal lamina propria, CX3CR1high resident Mfs possess anti-inflammatory properties and thereby support intestinal homeostasis. Unlike other tissue-resident Ms, transcription factors that regulate differentiation and function of CX3CR1high Ms in the large intestine are poorly understood. Thus, to identify transcription factors specifically expressed in CX3CR1high Ms among large intestinal lamina propria innate myeloid cells, we comprehensively analyzed the genes expression profiles in CX3CR1high Ms, CX3CR1- CD11b+ CD11c+ cells, CD11b- CD11chigh DCs, and CD11b+CD11c- cells.
Heme ameliorates dextran sodium sulfate-induced colitis through providing intestinal macrophages with noninflammatory profiles.
Specimen part
View SamplesTo determine the functions of Spi-C in innate immune responses, we investigated the overall gene expression patterns in M-CSF-BMDMFs prepared from Spicflox/flox and Lyz2-cre; Spicflox/flox mice. M-CSF-BMDMFs were stimulated with or without LPS following heme treatment and used for RNA-seq analysis. Overall design: Control and Spic–/– BMDMF pretreated with 40 µM hemin for 18 h were stimulated with (designated 'CNT_4' and 'cKO_4', respectively) or without (designated 'CNT_0' and 'cKO_0', respectively) 100 ng/ml LPS for 4 h.
Heme ameliorates dextran sodium sulfate-induced colitis through providing intestinal macrophages with noninflammatory profiles.
Specimen part, Treatment, Subject
View SamplesOur previous investigation indicated that high-virulence C. gattii (C. gattii R265) tend to reside in the alveoli, whereas low-virulence C. gattii (C. gattii 5815) tend to be washed out from the alveoli and move into the central side of the respiratory system of the mice. Furthermore, C. gattii R265 and 5815 infected mice showed much lesser macrophage response than C. neoformans H99 infected mice. To elucidate the mechanism of this phenomenon from the viewpoint of genetic analysis, we performed this microarray assay.
A linking bridge between histopathological analysis and molecular assay in microbiology.
Sex, Age, Specimen part, Treatment
View SamplesGlobal gene expression data from 7-day old light-grown liquid cultured seedlings treated with or without auxin (5M IAA) for 2 h.
AUXIN RESPONSE FACTOR 2 (ARF2): a pleiotropic developmental regulator.
No sample metadata fields
View SamplesThe B1 SOX transcription factors SOX1/2/3/19 have been implicated in various processes of early embryogenesis. However, their regulatory functions in stages from the blastula to early neurula remain largely unknown, primarily because loss-of-function studies have not been informative to date. In our present study, we systematically knocked down the B1 sox genes in zebrafish. Only the quadruple knockdown of the four B1 sox genes sox2/3/19a/19b, which are active in the early embryo, resulted in very severe developmental abnormalities, confirming that the B1 sox genes are functionally redundant. We characterized the sox2/3/19a/19b quadruple knockdown embryos in detail by examining the changes in gene expression through microarray analysis as well as in situ hybridization.
B1 SOX coordinate cell specification with patterning and morphogenesis in the early zebrafish embryo.
Specimen part
View SamplesGlobal gene expression data from 7-day old light-grown liquid cultured seedlings treated with or without auxin (5M IAA) for 2 h. Columbia (WT) and Auxin response factor 2 (ARF2) T-DNA insertion mutant (arf2-6 ) were used for this study. Each experimental condition has three true replicates for a total of 12 hybridizations.
AUXIN RESPONSE FACTOR 2 (ARF2): a pleiotropic developmental regulator.
No sample metadata fields
View Samples