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900
PMID-9916078
[ { "id": "PMID-9916078__text", "type": "abstract", "text": [ "Involvement of mitogen-activated protein kinase pathways in interleukin-8 production by human monocytes and polymorphonuclear cells stimulated with lipopolysaccharide or Mycoplasma fermentans membrane lipoproteins. \nInterleukin-8 (IL-8) is a chemokine that belongs to the alpha-chemokine or CXC subfamily and is produced by a wide variety of human cells, including monocytes and polymorphonuclear cells (PMN). IL-8 is secreted in response to inflammatory stimuli, notably bacterial products such as lipopolysaccharide (LPS), but little is known about the mechanisms by which these agents mediate IL-8 induction. In this report, we show that Mycoplasma fermentans lipid-associated membrane proteins (LAMPf) induce the production of high levels of IL-8 by THP-1 (human monocyte) cells and PMN at the same extent as LPS. It was previously demonstrated that stimulation of monocytic cells with either LPS or LAMPf led to a series of common downstream signaling events, including the activation of protein tyrosine kinase and of mitogen-activated protein kinase cascades. By using PD-98059 and SB203580, two potent and selective inhibitors of MEK1 (a kinase upstream of ERK1/2) and p38, respectively, we have demonstrated that both ERK1/2 and p38 cascades play a key role in the production of IL-8 by monocytes and PMN stimulated with bacterial fractions. " ], "offsets": [ [ 0, 1351 ] ] } ]
[ { "id": "PMID-9916078_T1", "type": "Protein", "text": [ "interleukin-8" ], "offsets": [ [ 60, 73 ] ], "normalized": [] }, { "id": "PMID-9916078_T2", "type": "Protein", "text": [ "Interleukin-8" ], "offsets": [ [ 216, 229 ] ], "normalized": [] }, { "id": "PMID-9916078_T3", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 231, 235 ] ], "normalized": [] }, { "id": "PMID-9916078_T4", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 410, 414 ] ], "normalized": [] }, { "id": "PMID-9916078_T5", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 596, 600 ] ], "normalized": [] }, { "id": "PMID-9916078_T6", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 746, 750 ] ], "normalized": [] }, { "id": "PMID-9916078_T7", "type": "Protein", "text": [ "MEK1" ], "offsets": [ [ 1138, 1142 ] ], "normalized": [] }, { "id": "PMID-9916078_T8", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 1288, 1292 ] ], "normalized": [] } ]
[ { "id": "PMID-9916078_E1", "type": "Regulation", "trigger": { "text": [ "Involvement" ], "offsets": [ [ 0, 11 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916078_E2" } ] }, { "id": "PMID-9916078_E2", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 74, 84 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916078_T1" } ] }, { "id": "PMID-9916078_E3", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 312, 320 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916078_T3" } ] }, { "id": "PMID-9916078_E4", "type": "Localization", "trigger": { "text": [ "secreted" ], "offsets": [ [ 418, 426 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916078_T4" } ] }, { "id": "PMID-9916078_E5", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 427, 441 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916078_E4" } ] }, { "id": "PMID-9916078_E6", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 601, 610 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916078_T5" } ] }, { "id": "PMID-9916078_E7", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 706, 712 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916078_E8" } ] }, { "id": "PMID-9916078_E8", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 717, 727 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916078_T6" } ] }, { "id": "PMID-9916078_E9", "type": "Positive_regulation", "trigger": { "text": [ "high levels" ], "offsets": [ [ 731, 742 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916078_E8" } ] }, { "id": "PMID-9916078_E10", "type": "Negative_regulation", "trigger": { "text": [ "inhibitors" ], "offsets": [ [ 1124, 1134 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916078_T7" } ] }, { "id": "PMID-9916078_E11", "type": "Positive_regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 1262, 1266 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916078_E12" } ] }, { "id": "PMID-9916078_E12", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1274, 1284 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916078_T8" } ] } ]
[ { "id": "PMID-9916078_1", "entity_ids": [ "PMID-9916078_T3", "PMID-9916078_T2" ] } ]
[]
901
PMID-9916709
[ { "id": "PMID-9916709__text", "type": "abstract", "text": [ "T cell priming enhances IL-4 gene expression by increasing nuclear factor of activated T cells. \nThe repetitive activation of T cells (priming) enhances the expression of many cytokines, such as IL-4, but not others, such as IL-2. Molecular mechanisms underlying selective expression of cytokines by T cells remain poorly understood. Here we show that priming of CD4 T cells selectively enhances IL-4 expression relative to IL-2 expression by a transcriptional mechanism involving nuclear factor of activated T cells (NFAT) proteins. As detected by in vivo footprinting, priming markedly increases the activation-dependent engagement of the P0 and P1 NFAT-binding elements of the IL-4 promoter. Moreover, each proximal P element is essential for optimal IL-4 promoter activity. Activated primed CD4 T cells contain more NFAT1 and support greater NFAT-directed transcription than unprimed CD4 T cells, while activator protein 1 binding and activator protein 1-mediated transcription by both cell types is similar. Increased expression of wild-type NFAT1 substantially increases IL-4 promoter activity in unprimed CD4 T cells, suggesting NFAT1 may be limiting for IL-4 gene expression in this cell type. Furthermore, a truncated form of NFAT1 acts as a dominant-negative, reducing IL-4 promoter activity in primed CD4 T cells and confirming the importance of endogenous NFAT to increased IL-4 gene expression by effector T cells. NFAT1 appears to be the major NFAT family member responsible for the initial increased expression of IL-4 by primed CD4 T cells. " ], "offsets": [ [ 0, 1557 ] ] } ]
[ { "id": "PMID-9916709_T1", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 24, 28 ] ], "normalized": [] }, { "id": "PMID-9916709_T2", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 195, 199 ] ], "normalized": [] }, { "id": "PMID-9916709_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 225, 229 ] ], "normalized": [] }, { "id": "PMID-9916709_T4", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 363, 366 ] ], "normalized": [] }, { "id": "PMID-9916709_T5", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 396, 400 ] ], "normalized": [] }, { "id": "PMID-9916709_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 424, 428 ] ], "normalized": [] }, { "id": "PMID-9916709_T7", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 680, 684 ] ], "normalized": [] }, { "id": "PMID-9916709_T8", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 754, 758 ] ], "normalized": [] }, { "id": "PMID-9916709_T9", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 795, 798 ] ], "normalized": [] }, { "id": "PMID-9916709_T10", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 820, 825 ] ], "normalized": [] }, { "id": "PMID-9916709_T11", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 888, 891 ] ], "normalized": [] }, { "id": "PMID-9916709_T12", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 1047, 1052 ] ], "normalized": [] }, { "id": "PMID-9916709_T13", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1077, 1081 ] ], "normalized": [] }, { "id": "PMID-9916709_T14", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1112, 1115 ] ], "normalized": [] }, { "id": "PMID-9916709_T15", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 1136, 1141 ] ], "normalized": [] }, { "id": "PMID-9916709_T16", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1162, 1166 ] ], "normalized": [] }, { "id": "PMID-9916709_T17", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 1235, 1240 ] ], "normalized": [] }, { "id": "PMID-9916709_T18", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1279, 1283 ] ], "normalized": [] }, { "id": "PMID-9916709_T19", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1312, 1315 ] ], "normalized": [] }, { "id": "PMID-9916709_T20", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1386, 1390 ] ], "normalized": [] }, { "id": "PMID-9916709_T21", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 1428, 1433 ] ], "normalized": [] }, { "id": "PMID-9916709_T22", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1529, 1533 ] ], "normalized": [] }, { "id": "PMID-9916709_T23", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1544, 1547 ] ], "normalized": [] }, { "id": "PMID-9916709_T33", "type": "Entity", "text": [ "P0" ], "offsets": [ [ 641, 643 ] ], "normalized": [] }, { "id": "PMID-9916709_T34", "type": "Entity", "text": [ "P1 NFAT-binding elements" ], "offsets": [ [ 648, 672 ] ], "normalized": [] }, { "id": "PMID-9916709_T35", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 685, 693 ] ], "normalized": [] }, { "id": "PMID-9916709_T37", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 759, 767 ] ], "normalized": [] }, { "id": "PMID-9916709_T42", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1082, 1090 ] ], "normalized": [] }, { "id": "PMID-9916709_T46", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1284, 1292 ] ], "normalized": [] } ]
[ { "id": "PMID-9916709_E1", "type": "Positive_regulation", "trigger": { "text": [ "enhances" ], "offsets": [ [ 15, 23 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_E2" } ] }, { "id": "PMID-9916709_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 34, 44 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_T1" } ] }, { "id": "PMID-9916709_E3", "type": "Positive_regulation", "trigger": { "text": [ "enhances" ], "offsets": [ [ 144, 152 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_E6" } ] }, { "id": "PMID-9916709_E4", "type": "Positive_regulation", "trigger": { "text": [ "enhances" ], "offsets": [ [ 144, 152 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_E5" } ] }, { "id": "PMID-9916709_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 157, 167 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_T2" } ] }, { "id": "PMID-9916709_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 157, 167 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_T3" } ] }, { "id": "PMID-9916709_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 429, 439 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_T6" } ] }, { "id": "PMID-9916709_E8", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 588, 597 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_E14" } ] }, { "id": "PMID-9916709_E9", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 588, 597 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_E13" } ] }, { "id": "PMID-9916709_E10", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 602, 612 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_T7" }, { "role": "Site", "ref_id": "PMID-9916709_T35" } ] }, { "id": "PMID-9916709_E11", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 613, 622 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_E13" }, { "role": "Cause", "ref_id": "PMID-9916709_E10" } ] }, { "id": "PMID-9916709_E12", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 613, 622 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_E14" }, { "role": "Cause", "ref_id": "PMID-9916709_E10" } ] }, { "id": "PMID-9916709_E13", "type": "Binding", "trigger": { "text": [ "engagement" ], "offsets": [ [ 623, 633 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_T7" }, { "role": "Site", "ref_id": "PMID-9916709_T34" } ] }, { "id": "PMID-9916709_E14", "type": "Binding", "trigger": { "text": [ "engagement" ], "offsets": [ [ 623, 633 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_T7" }, { "role": "Site", "ref_id": "PMID-9916709_T33" } ] }, { "id": "PMID-9916709_E15", "type": "Positive_regulation", "trigger": { "text": [ "essential" ], "offsets": [ [ 732, 741 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_T8" }, { "role": "Cause", "ref_id": "PMID-9916709_T7" }, { "role": "Site", "ref_id": "PMID-9916709_T37" }, { "role": "CSite", "ref_id": "PMID-9916709_T34" } ] }, { "id": "PMID-9916709_E16", "type": "Positive_regulation", "trigger": { "text": [ "essential" ], "offsets": [ [ 732, 741 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_T8" }, { "role": "Cause", "ref_id": "PMID-9916709_T7" }, { "role": "Site", "ref_id": "PMID-9916709_T37" }, { "role": "CSite", "ref_id": "PMID-9916709_T33" } ] }, { "id": "PMID-9916709_E17", "type": "Gene_expression", "trigger": { "text": [ "contain" ], "offsets": [ [ 807, 814 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_T10" } ] }, { "id": "PMID-9916709_E18", "type": "Positive_regulation", "trigger": { "text": [ "more" ], "offsets": [ [ 815, 819 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_E17" } ] }, { "id": "PMID-9916709_E19", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1023, 1033 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_T12" } ] }, { "id": "PMID-9916709_E20", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1067, 1076 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_T13" }, { "role": "Cause", "ref_id": "PMID-9916709_E19" }, { "role": "Site", "ref_id": "PMID-9916709_T42" } ] }, { "id": "PMID-9916709_E21", "type": "Negative_regulation", "trigger": { "text": [ "limiting" ], "offsets": [ [ 1149, 1157 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_E22" }, { "role": "Cause", "ref_id": "PMID-9916709_T15" } ] }, { "id": "PMID-9916709_E22", "type": "Gene_expression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 1167, 1182 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_T13" } ] }, { "id": "PMID-9916709_E23", "type": "Negative_regulation", "trigger": { "text": [ "reducing" ], "offsets": [ [ 1270, 1278 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_T18" }, { "role": "Site", "ref_id": "PMID-9916709_T46" } ] }, { "id": "PMID-9916709_E24", "type": "Regulation", "trigger": { "text": [ "importance" ], "offsets": [ [ 1343, 1353 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_E25" } ] }, { "id": "PMID-9916709_E25", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1376, 1385 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_E26" } ] }, { "id": "PMID-9916709_E26", "type": "Gene_expression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 1391, 1406 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_T20" } ] }, { "id": "PMID-9916709_E27", "type": "Regulation", "trigger": { "text": [ "responsible" ], "offsets": [ [ 1477, 1488 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_E28" }, { "role": "Cause", "ref_id": "PMID-9916709_T21" } ] }, { "id": "PMID-9916709_E28", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1505, 1514 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_E29" } ] }, { "id": "PMID-9916709_E29", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1515, 1525 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9916709_T22" } ] } ]
[]
[]
902
PMID-9919536
[ { "id": "PMID-9919536__text", "type": "abstract", "text": [ "Inhibition of NF-kappa B activation in vitro and in vivo: role of 26S proteasome. \nIt is becoming increasingly apparent that NF-kappa B plays a critical role in regulating the inflammatory response. Data obtained from studies in our laboratories demonstrate that the proteasome plays an important role in the inflammatory cascade by regulating the activation of NF-kappa B. Indeed, the availability of selective and orally active proteasome inhibitors should prove useful in delineating the roles of the proteasome and NF-kappa B in other pathophysiological conditions such as cancer and heart disease. " ], "offsets": [ [ 0, 603 ] ] } ]
[]
[]
[]
[]
903
PMID-9933632
[ { "id": "PMID-9933632__text", "type": "abstract", "text": [ "NF-kappaB activation is a critical regulator of human granulocyte apoptosis in vitro. \nDuring beneficial inflammation, potentially tissue-damaging granulocytes undergo apoptosis before being cleared by phagocytes in a non-phlogistic manner. Here we show that the rate of constitutive apoptosis in human neutrophils and eosinophils is greatly accelerated in both a rapid and concentration-dependent manner by the fungal metabolite gliotoxin, but not by its inactive analog methylthiogliotoxin. This induction of apoptosis was abolished by the caspase inhibitor zVAD-fmk, correlated with the inhibition of nuclear factor-kappa B (NF-kappaB), and was mimicked by a cell permeable inhibitory peptide of NF-kappaB, SN-50; other NF-kappaB inhibitors, curcumin and pyrrolidine dithiocarbamate; and the proteasome inhibitor, MG-132. Gliotoxin also augmented dramatically the early (2-6 h) pro-apoptotic effects of tumor necrosis factor-alpha (TNF-alpha) in neutrophils and unmasked the ability of TNF-alpha to induce eosinophil apoptosis. In neutrophils, TNF-alpha caused a gliotoxin-inhibitable activation of an inducible form of NF-kappaB, a response that may underlie the ability of TNF-alpha to delay apoptosis at later times (12-24 h) and limit its early killing effect. Furthermore, cycloheximide displayed a similar capacity to enhance TNF-alpha induced neutrophil apoptosis even at time points when cycloheximide alone had no pro-apoptotic effect, suggesting that NF-kappaB may regulate the production of protein(s) which protect neutrophils from the cytotoxic effects of TNF-alpha. These data shed light on the biochemical and molecular mechanisms regulating human granulocyte apoptosis and, in particular, indicate that the transcription factor NF-kappaB plays a crucial role in regulating the physiological cell death pathway in granulocytes. " ], "offsets": [ [ 0, 1846 ] ] } ]
[ { "id": "PMID-9933632_T1", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 906, 933 ] ], "normalized": [] }, { "id": "PMID-9933632_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 935, 944 ] ], "normalized": [] }, { "id": "PMID-9933632_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 989, 998 ] ], "normalized": [] }, { "id": "PMID-9933632_T4", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1047, 1056 ] ], "normalized": [] }, { "id": "PMID-9933632_T5", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1178, 1187 ] ], "normalized": [] }, { "id": "PMID-9933632_T6", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1335, 1344 ] ], "normalized": [] }, { "id": "PMID-9933632_T7", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1572, 1581 ] ], "normalized": [] } ]
[ { "id": "PMID-9933632_E1", "type": "Positive_regulation", "trigger": { "text": [ "underlie the ability" ], "offsets": [ [ 1154, 1174 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9933632_T5" } ] } ]
[ { "id": "PMID-9933632_1", "entity_ids": [ "PMID-9933632_T1", "PMID-9933632_T2" ] } ]
[]
904
PMID-9952372
[ { "id": "PMID-9952372__text", "type": "abstract", "text": [ "Lactobacilli and vaginal host defense: activation of the human immunodeficiency virus type 1 long terminal repeat, cytokine production, and NF-kappaB. \nLactobacilli, a component of the normal vaginal flora, can activate the human immunodeficiency virus (HIV)-1 long terminal repeat (LTR) in the Jurkat T lymphocyte and THP-1 macrophage cell lines. Activation of the LTR in Jurkat cells was strongly enhanced by vanadate and inhibited by catalase, implicating H2O2. In contrast, activation in THP-1 cells occurred in the absence of vanadate and was unaffected by catalase. The active material partitioned into the phenol layer on hot aqueous phenol extraction. Lactobacilli also increased tumor necrosis factor-alphaand interleukin-1betaproduction and activated NF-kappaB in THP-1 cells and increased tumor necrosis factor-alphaproduction by human monocytes. Human vaginal fluid specimens had comparable properties, which correlated with their bacterial content. These findings suggest the presence in vaginal fluid of agent(s) derived from indigenous bacteria that can activate the HIV-1 LTR, cytokine production, and NF-kappaB in cells of macrophage lineage, with possible influence on vaginal physiology and host defense. " ], "offsets": [ [ 0, 1224 ] ] } ]
[ { "id": "PMID-9952372_T1", "type": "Protein", "text": [ "catalase" ], "offsets": [ [ 437, 445 ] ], "normalized": [] }, { "id": "PMID-9952372_T2", "type": "Protein", "text": [ "catalase" ], "offsets": [ [ 562, 570 ] ], "normalized": [] }, { "id": "PMID-9952372_T3", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 688, 715 ] ], "normalized": [] }, { "id": "PMID-9952372_T4", "type": "Protein", "text": [ "interleukin-1beta" ], "offsets": [ [ 719, 736 ] ], "normalized": [] }, { "id": "PMID-9952372_T5", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 800, 827 ] ], "normalized": [] } ]
[ { "id": "PMID-9952372_E1", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 678, 687 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9952372_E3" } ] }, { "id": "PMID-9952372_E2", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 678, 687 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9952372_E4" } ] }, { "id": "PMID-9952372_E3", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 736, 746 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9952372_T4" } ] }, { "id": "PMID-9952372_E4", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 736, 746 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9952372_T3" } ] }, { "id": "PMID-9952372_E5", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 790, 799 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9952372_E6" } ] }, { "id": "PMID-9952372_E6", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 827, 837 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9952372_T5" } ] } ]
[]
[]
905
PMID-9971788
[ { "id": "PMID-9971788__text", "type": "abstract", "text": [ "High-level replication of human immunodeficiency virus in thymocytes requires NF-kappaB activation through interaction with thymic epithelial cells. \nWe have previously demonstrated that interaction of infected thymocytes with autologous thymic epithelial cells (TEC) is a prerequisite for a high level of human immunodeficiency virus type 1 (HIV-1) replication in thymocytes (M.Rothe, L.Chene, M.Nugeyre, F.Barre-Sinoussi, and N.Israel, J.Virol.72:5852-5861, 1998). We report here that this activation of HIV replication takes place at the transcriptional level through activation of the Rel/NF-kappaB transcription factors. We first demonstrate that an HIV-1 provirus (SF-2 strain) very effectively replicates in thymocytes cocultured with TEC whereas this provirus, with kappaB sites deleted, fails to replicate. We provide evidence that several NF-kappaB complexes are constitutively found in the nuclei of thymocytes either freshly isolated from the thymus or maintained in coculture with autologous or heterologous TEC. The prevalent complex is the heterodimer p50-p65. NF-kappaB activity is tightly correlated with the transcriptional activity of a long terminal repeat (LTR) of HIV-1 transfected in thymocytes. The cotransfection of this LTR with a mutated IkappaBalpha molecule formally demonstrates that LTR transactivation is regulated by members of the Rel/NF-kappaB family in thymocytes. We also showed that tumor necrosis factor (TNF) and to a lesser extent interleukin-1 (IL-1), secreted within the coculture, induce NF-kappaB activity and a correlative LTR transactivation. However IL-7, a crucial factor for thymopoiesis that is secreted mainly by TEC, is a necessary cofactor for NF-kappaB activation elicited by TNF or IL-1. Together, these data indicate that NF-kappaB activation, required for a high level of HIV replication in thymocytes, is regulated in a specific manner in the thymic microenvironment which provides the necessary cytokines: TNF, IL-1, and IL-7. " ], "offsets": [ [ 0, 1987 ] ] } ]
[ { "id": "PMID-9971788_T1", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1067, 1070 ] ], "normalized": [] }, { "id": "PMID-9971788_T2", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1071, 1074 ] ], "normalized": [] }, { "id": "PMID-9971788_T3", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 1265, 1277 ] ], "normalized": [] }, { "id": "PMID-9971788_T4", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 1598, 1602 ] ], "normalized": [] }, { "id": "PMID-9971788_T5", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 1981, 1985 ] ], "normalized": [] } ]
[ { "id": "PMID-9971788_E1", "type": "Positive_regulation", "trigger": { "text": [ "cotransfection" ], "offsets": [ [ 1223, 1237 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9971788_E2" } ] }, { "id": "PMID-9971788_E2", "type": "Gene_expression", "trigger": { "text": [ "cotransfection" ], "offsets": [ [ 1223, 1237 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9971788_T3" } ] }, { "id": "PMID-9971788_E3", "type": "Localization", "trigger": { "text": [ "secreted" ], "offsets": [ [ 1646, 1654 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9971788_T4" } ] }, { "id": "PMID-9971788_E4", "type": "Gene_expression", "trigger": { "text": [ "provides" ], "offsets": [ [ 1932, 1940 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9971788_T5" } ] } ]
[]
[]
906
PMID-9973520
[ { "id": "PMID-9973520__text", "type": "abstract", "text": [ "Cross-linking of CD44 on rheumatoid synovial cells up-regulates VCAM-1. \nCD44 is a ubiquitous molecule also known as hyaluronic acid or homing receptor. However, the cellular functions and its role in inflammation, for example, rheumatoid synovitis, are currently unknown. In this study, we propose a novel function for CD44. Using synovial cells from rheumatoid arthritis (RA) patients, we demonstrated that CD44 cross-linking and binding to hyaluronan augmented VCAM-1 expression and subsequently VCAM-1-mediated cell adhesion. Briefly, we found that 1) rheumatoid synovial cells highly expressed CD44; 2) cross-linking of CD44 markedly but transiently augmented VCAM-1 expression and its mRNA transcription much more than did IL-1beta and TNF-alpha; 3) hyaluronan, especially when fragmented, also up-regulated VCAM-1; 4) CD44 activated the transcription factor AP-1; and 5) the integrin-dependent adhesive function of RA synovial cells to T cells was also amplified by CD44 cross-linking. These results indicate that the adhesion of RA synovial cells to matrices such as hyaluronic acid through CD44 could up-regulate VCAM-1 expression and VCAM-1-mediated adhesion to T cells, which might in turn cause activation of T cells and synovial cells in RA synovitis. We therefore propose that such cross-talking among distinct adhesion molecules may be involved in the pathogenesis of inflammation, including RA synovitis. " ], "offsets": [ [ 0, 1421 ] ] } ]
[ { "id": "PMID-9973520_T1", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 17, 21 ] ], "normalized": [] }, { "id": "PMID-9973520_T2", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 64, 70 ] ], "normalized": [] }, { "id": "PMID-9973520_T3", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 73, 77 ] ], "normalized": [] }, { "id": "PMID-9973520_T4", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 320, 324 ] ], "normalized": [] }, { "id": "PMID-9973520_T5", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 409, 413 ] ], "normalized": [] }, { "id": "PMID-9973520_T6", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 464, 470 ] ], "normalized": [] }, { "id": "PMID-9973520_T7", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 499, 505 ] ], "normalized": [] }, { "id": "PMID-9973520_T8", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 599, 603 ] ], "normalized": [] }, { "id": "PMID-9973520_T9", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 625, 629 ] ], "normalized": [] }, { "id": "PMID-9973520_T10", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 665, 671 ] ], "normalized": [] }, { "id": "PMID-9973520_T11", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 729, 737 ] ], "normalized": [] }, { "id": "PMID-9973520_T12", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 742, 751 ] ], "normalized": [] }, { "id": "PMID-9973520_T13", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 814, 820 ] ], "normalized": [] }, { "id": "PMID-9973520_T14", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 825, 829 ] ], "normalized": [] }, { "id": "PMID-9973520_T15", "type": "Protein", "text": [ "AP-1" ], "offsets": [ [ 865, 869 ] ], "normalized": [] }, { "id": "PMID-9973520_T16", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 973, 977 ] ], "normalized": [] }, { "id": "PMID-9973520_T17", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 1099, 1103 ] ], "normalized": [] }, { "id": "PMID-9973520_T18", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1122, 1128 ] ], "normalized": [] }, { "id": "PMID-9973520_T19", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1144, 1150 ] ], "normalized": [] } ]
[ { "id": "PMID-9973520_E1", "type": "Positive_regulation", "trigger": { "text": [ "up-regulates" ], "offsets": [ [ 51, 63 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_T2" } ] }, { "id": "PMID-9973520_E2", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 414, 427 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_T5" } ] }, { "id": "PMID-9973520_E3", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 432, 439 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_T5" } ] }, { "id": "PMID-9973520_E4", "type": "Positive_regulation", "trigger": { "text": [ "augmented" ], "offsets": [ [ 454, 463 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_E5" }, { "role": "Cause", "ref_id": "PMID-9973520_E3" } ] }, { "id": "PMID-9973520_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 471, 481 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_T7" } ] }, { "id": "PMID-9973520_E6", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 589, 598 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_T8" } ] }, { "id": "PMID-9973520_E7", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 608, 621 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_T9" } ] }, { "id": "PMID-9973520_E8", "type": "Positive_regulation", "trigger": { "text": [ "augmented" ], "offsets": [ [ 655, 664 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_E14" }, { "role": "Cause", "ref_id": "PMID-9973520_E7" } ] }, { "id": "PMID-9973520_E9", "type": "Positive_regulation", "trigger": { "text": [ "augmented" ], "offsets": [ [ 655, 664 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_E16" }, { "role": "Cause", "ref_id": "PMID-9973520_E7" } ] }, { "id": "PMID-9973520_E10", "type": "Positive_regulation", "trigger": { "text": [ "augmented" ], "offsets": [ [ 655, 664 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_E12" }, { "role": "Cause", "ref_id": "PMID-9973520_E7" } ] }, { "id": "PMID-9973520_E11", "type": "Positive_regulation", "trigger": { "text": [ "augmented" ], "offsets": [ [ 655, 664 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_E15" }, { "role": "Cause", "ref_id": "PMID-9973520_E7" } ] }, { "id": "PMID-9973520_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 672, 682 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_T10" } ] }, { "id": "PMID-9973520_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 672, 682 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_T11" } ] }, { "id": "PMID-9973520_E14", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 696, 709 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_T10" } ] }, { "id": "PMID-9973520_E15", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 696, 709 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_T11" } ] }, { "id": "PMID-9973520_E16", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 696, 709 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_T12" } ] }, { "id": "PMID-9973520_E17", "type": "Positive_regulation", "trigger": { "text": [ "up-regulated" ], "offsets": [ [ 801, 813 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_T13" } ] }, { "id": "PMID-9973520_E18", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 830, 839 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_T15" }, { "role": "Cause", "ref_id": "PMID-9973520_T14" } ] }, { "id": "PMID-9973520_E19", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 978, 991 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_T16" } ] }, { "id": "PMID-9973520_E20", "type": "Positive_regulation", "trigger": { "text": [ "up-regulate" ], "offsets": [ [ 1110, 1121 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_E21" } ] }, { "id": "PMID-9973520_E21", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1129, 1139 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9973520_T18" } ] } ]
[]
[]
907
PMID-9974401
[ { "id": "PMID-9974401__text", "type": "abstract", "text": [ "Oleic acid inhibits endothelial activation : A direct vascular antiatherogenic mechanism of a nutritional component in the mediterranean diet. \nBecause oleic acid is implicated in the antiatherogenic effects attributed to the Mediterranean diet, we investigated whether this fatty acid can modulate endothelial activation, ie, the concerted expression of gene products involved in leukocyte recruitment and early atherogenesis. We incubated sodium oleate with human umbilical vein endothelial cells for 0 to 72 hours, followed by coincubation of oleate with human recombinant tumor necrosis factor, interleukin (IL)-1alpha, IL-1beta, IL-4, Escherichia coli lipopolysaccharide (LPS), or phorbol 12-myristate 13-acetate for a further 6 to 24 hours. The endothelial expression of vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and intercellular adhesion molecule-1 was monitored by cell surface enzyme immunoassays or flow cytometry, and steady-state levels of VCAM-1 mRNA were assessed by Northern blot analysis. At 10 to 100 micromol/L for >24 hours, oleate inhibited the expression of all adhesion molecules tested. After a 72-hour incubation with oleate and a further 16-hour incubation with oleate plus 1 microg/mL LPS, VCAM-1 expression was reduced by >40% compared with control. Adhesion of monocytoid U937 cells to LPS-treated endothelial cells was reduced concomitantly. Oleate also produced a quantitatively similar reduction of VCAM-1 mRNA levels on Northern blot analysis and inhibited nuclear factor-kappaB activation on electrophoretic mobility shift assays. Incubation of endothelial cells with oleate for 72 hours decreased the relative proportions of saturated (palmitic and stearic) acids in total cell lipids and increased the proportions of oleate in total cell lipids without significantly changing the relative proportions of polyunsaturated fatty acids. Although less potent than polyunsaturated fatty acids in inhibiting endothelial activation, oleic acid may contribute to the prevention of atherogenesis through selective displacement of saturated fatty acids in cell membrane phospholipids and a consequent modulation of gene expression for molecules involved in monocyte recruitment. " ], "offsets": [ [ 0, 2218 ] ] } ]
[ { "id": "PMID-9974401_T1", "type": "Protein", "text": [ "interleukin (IL)-1alpha" ], "offsets": [ [ 599, 622 ] ], "normalized": [] }, { "id": "PMID-9974401_T2", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 624, 632 ] ], "normalized": [] }, { "id": "PMID-9974401_T3", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 634, 638 ] ], "normalized": [] }, { "id": "PMID-9974401_T4", "type": "Protein", "text": [ "vascular cell adhesion molecule-1" ], "offsets": [ [ 777, 810 ] ], "normalized": [] }, { "id": "PMID-9974401_T5", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 812, 818 ] ], "normalized": [] }, { "id": "PMID-9974401_T6", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 821, 831 ] ], "normalized": [] }, { "id": "PMID-9974401_T7", "type": "Protein", "text": [ "intercellular adhesion molecule-1" ], "offsets": [ [ 837, 870 ] ], "normalized": [] }, { "id": "PMID-9974401_T8", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 967, 973 ] ], "normalized": [] }, { "id": "PMID-9974401_T9", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1231, 1237 ] ], "normalized": [] }, { "id": "PMID-9974401_T10", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1445, 1451 ] ], "normalized": [] } ]
[ { "id": "PMID-9974401_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 763, 773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9974401_T6" } ] }, { "id": "PMID-9974401_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 763, 773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9974401_T7" } ] }, { "id": "PMID-9974401_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 763, 773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9974401_T5" } ] }, { "id": "PMID-9974401_E4", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 957, 963 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9974401_T8" } ] }, { "id": "PMID-9974401_E5", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1066, 1075 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9974401_E9" } ] }, { "id": "PMID-9974401_E6", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1066, 1075 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9974401_E8" } ] }, { "id": "PMID-9974401_E7", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1066, 1075 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9974401_E10" } ] }, { "id": "PMID-9974401_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1080, 1090 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9974401_T5" } ] }, { "id": "PMID-9974401_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1080, 1090 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9974401_T6" } ] }, { "id": "PMID-9974401_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1080, 1090 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9974401_T7" } ] }, { "id": "PMID-9974401_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1238, 1248 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9974401_T9" } ] }, { "id": "PMID-9974401_E12", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1253, 1260 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9974401_E11" } ] }, { "id": "PMID-9974401_E13", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 1432, 1441 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9974401_T10" } ] } ]
[ { "id": "PMID-9974401_1", "entity_ids": [ "PMID-9974401_T5", "PMID-9974401_T4" ] } ]
[]