{"owner": "ArrayExpress Uploader", "pop_total": 0, "id": 2555, "factors": [{"GSM1058708": {"DONOR": "4", "TREATMENT": "FK506_anti-CD3/CD28", "SUBJECT": "4"}}, {"GSM1058707": {"DONOR": "4", "TREATMENT": "CsA_anti-CD3/CD28", "SUBJECT": "4"}}, {"GSM1058706": {"DONOR": "4", "TREATMENT": "CRACi_anti-CD3/CD28", "SUBJECT": "4"}}, {"GSM1058705": {"DONOR": "4", "TREATMENT": "anti-CD3/CD28", "SUBJECT": "4"}}, {"GSM1058704": {"DONOR": "4", "TREATMENT": "Untreated", "SUBJECT": "4"}}, {"GSM1058703": {"DONOR": "3", "TREATMENT": "FK506_anti-CD3/CD28", "SUBJECT": "3"}}, {"GSM1058702": {"DONOR": "3", "TREATMENT": "CsA_anti-CD3/CD28", "SUBJECT": "3"}}, {"GSM105870": {"DONOR": "3", "TREATMENT": "CRACi_anti-CD3/CD28", "SUBJECT": "3"}}, {"GSM1058700": {"DONOR": "3", "TREATMENT": "anti-CD3/CD28", "SUBJECT": "3"}}, {"GSM1058699": {"DONOR": "3", "TREATMENT": "Untreated", "SUBJECT": "3"}}, {"GSM1058698": {"DONOR": "2", "TREATMENT": "FK506_anti-CD3/CD28", "SUBJECT": "2"}}, {"GSM1058697": {"DONOR": "2", "TREATMENT": "CRACi_anti-CD3/CD28", "SUBJECT": "2"}}, {"GSM1058696": {"DONOR": "2", "TREATMENT": "anti-CD3/CD28", "SUBJECT": "2"}}, {"GSM1058695": {"DONOR": "1", "TREATMENT": "FK506_anti-CD3/CD28", "SUBJECT": "1"}}, {"GSM1058694": {"DONOR": "1", "TREATMENT": "CsA_anti-CD3/CD28", "SUBJECT": "1"}}, {"GSM1058693": {"DONOR": "1", "TREATMENT": "CRACi_anti-CD3/CD28", "SUBJECT": "1"}}, {"GSM1058692": {"DONOR": "1", "TREATMENT": "anti-CD3/CD28", "SUBJECT": "1"}}, {"GSM105869": {"DONOR": "1", "TREATMENT": "Untreated", "SUBJECT": "1"}}], "ownerprofile_id": "arrayexpress_sid", "platform": 4, "summary_wrapped": "Store operated calcium entry (SOCE) downstream of T cell receptor (TCR) activation in T lymphocytes has been shown to be mediated mainly...", "pubmed_id": 23357789, "geo_gse_id": "E-GEOD-43210", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 3, "sample_count": 18, "tags": ["cell", "cytokine", "lymphocyte"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_gds_id": "", "slug": "characterization-of-a-novel-crac-inhibitor-that-po", "geo_id_plat": "E-GEOD-43210_A-AFFY-44", "name": "Characterization of A Novel CRAC Inhibitor that Potently Blocks Human T cell Activation and Effector Functions", "created": "Jul.12, 2014", "summary": "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. PBMC from healthy donors (n=4) were stimulated with anti-CD3/CD28 in the presence or absence of CRAC inhibitor, CsA or FK506 for 24 hrs", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-43210", "species": "human", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-43210/samples/"}