PubMed:7706710 JSONTXT

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{"project":"genia-medco-coref","denotations":[{"id":"C1","span":{"begin":272,"end":283},"obj":"NP"},{"id":"C2","span":{"begin":284,"end":288},"obj":"NP"},{"id":"C3","span":{"begin":466,"end":489},"obj":"NP"},{"id":"C4","span":{"begin":509,"end":526},"obj":"NP"},{"id":"C5","span":{"begin":528,"end":543},"obj":"NP"},{"id":"C6","span":{"begin":661,"end":679},"obj":"NP"},{"id":"C7","span":{"begin":681,"end":686},"obj":"NP"},{"id":"C8","span":{"begin":793,"end":807},"obj":"NP"},{"id":"C9","span":{"begin":915,"end":929},"obj":"NP"},{"id":"C10","span":{"begin":1211,"end":1225},"obj":"NP"},{"id":"C11","span":{"begin":1234,"end":1268},"obj":"NP"},{"id":"C12","span":{"begin":1278,"end":1281},"obj":"NP"},{"id":"C13","span":{"begin":1369,"end":1445},"obj":"NP"}],"relations":[{"id":"R1","pred":"coref-relat","subj":"C2","obj":"C1"},{"id":"R2","pred":"coref-ident","subj":"C4","obj":"C3"},{"id":"R3","pred":"coref-ident","subj":"C5","obj":"C3"},{"id":"R4","pred":"coref-relat","subj":"C7","obj":"C6"},{"id":"R5","pred":"coref-ident","subj":"C8","obj":"C5"},{"id":"R6","pred":"coref-ident","subj":"C9","obj":"C8"},{"id":"R7","pred":"coref-ident","subj":"C10","obj":"C9"},{"id":"R8","pred":"coref-pron","subj":"C12","obj":"C11"},{"id":"R9","pred":"coref-ident","subj":"C13","obj":"C3"}],"text":"Functional characterization of novel IL-2 transcriptional inhibitors.\nIL-2-mediated T cell proliferation is a critical early event in the inflammatory process. Formation of the NFAT-1 transcriptional complex on the IL-2 promoter is essential for IL-2 transcription. Using a cell line that is stably transfected with a trimer of the NFAT-1 regulatory element linked to a lac-Z reporter gene, we screened for inhibitors of NFAT-1-mediated beta-galactosidase activity. WIN 61058 and WIN 53071 were identified as microM inhibitors. These compounds also inhibited beta-galactosidase mRNA levels. Similar inhibition of NFAT-1-mediated gene expression was observed in a second cell line, which is stably transfected with NFAT-1 regulatory elements linked to the reporter gene for sCD8. At 10 microM, both compounds inhibited IL-2 mRNA and protein levels in the NFAT-1-linked lac-Z transfectants, and in human lymphocytes. Both compounds inhibited the mixed lymphocyte reaction, and this inhibition was reversed by exogenous IL-2. WIN 53071 inhibited IL-2 production induced in the calcium-dependent PMA and ionomycin pathway. Conversely, calcium-independent anti-CD28 Ab and PMA-induced IL-2 production was resistant. Both compounds altered the NFAT-1 transcriptional complex, causing its retarded mobility on gels. By these functional criteria, we believe we have identified two structurally distinct, novel inhibitors of NFAT-1-mediated transcription."}

{"project":"pubmed-sentences-benchmark","denotations":[{"id":"S1","span":{"begin":0,"end":69},"obj":"Sentence"},{"id":"S2","span":{"begin":70,"end":159},"obj":"Sentence"},{"id":"S3","span":{"begin":160,"end":265},"obj":"Sentence"},{"id":"S4","span":{"begin":266,"end":465},"obj":"Sentence"},{"id":"S5","span":{"begin":466,"end":527},"obj":"Sentence"},{"id":"S6","span":{"begin":528,"end":590},"obj":"Sentence"},{"id":"S7","span":{"begin":591,"end":778},"obj":"Sentence"},{"id":"S8","span":{"begin":779,"end":914},"obj":"Sentence"},{"id":"S9","span":{"begin":915,"end":1022},"obj":"Sentence"},{"id":"S10","span":{"begin":1023,"end":1118},"obj":"Sentence"},{"id":"S11","span":{"begin":1119,"end":1210},"obj":"Sentence"},{"id":"S12","span":{"begin":1211,"end":1308},"obj":"Sentence"},{"id":"S13","span":{"begin":1309,"end":1446},"obj":"Sentence"}],"text":"Functional characterization of novel IL-2 transcriptional inhibitors.\nIL-2-mediated T cell proliferation is a critical early event in the inflammatory process. Formation of the NFAT-1 transcriptional complex on the IL-2 promoter is essential for IL-2 transcription. Using a cell line that is stably transfected with a trimer of the NFAT-1 regulatory element linked to a lac-Z reporter gene, we screened for inhibitors of NFAT-1-mediated beta-galactosidase activity. WIN 61058 and WIN 53071 were identified as microM inhibitors. These compounds also inhibited beta-galactosidase mRNA levels. Similar inhibition of NFAT-1-mediated gene expression was observed in a second cell line, which is stably transfected with NFAT-1 regulatory elements linked to the reporter gene for sCD8. At 10 microM, both compounds inhibited IL-2 mRNA and protein levels in the NFAT-1-linked lac-Z transfectants, and in human lymphocytes. Both compounds inhibited the mixed lymphocyte reaction, and this inhibition was reversed by exogenous IL-2. WIN 53071 inhibited IL-2 production induced in the calcium-dependent PMA and ionomycin pathway. Conversely, calcium-independent anti-CD28 Ab and PMA-induced IL-2 production was resistant. Both compounds altered the NFAT-1 transcriptional complex, causing its retarded mobility on gels. By these functional criteria, we believe we have identified two structurally distinct, novel inhibitors of NFAT-1-mediated transcription."}

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