;PMID: 9224809 ;source_file_1873.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..35] = [t:0..35] ;1)sentence:[e:41..186] = [t:41..186] ;2)section:[e:190..233] = [t:190..233] ;3)section:[e:237..331] = [t:237..331] ;4)sentence:[e:335..505] = [t:335..505] ;5)sentence:[e:506..589] = [t:506..589] ;6)sentence:[e:590..896] = [t:590..896] ;7)sentence:[e:897..1153] = [t:897..1153] ;8)sentence:[e:1154..1320] = [t:1154..1320] ;9)sentence:[e:1321..1639] = [t:1321..1639] ;10)sentence:[e:1641..1792] = [t:1641..1792] ;11)sentence:[e:1793..2229] = [t:1793..2229] ;12)section:[e:2233..2277] = [t:2233..2277] ;section 0 Span:0..35 ;Mol Pharmacol. 1997 Jul;52(1):30-7. (SEC (FRAG (NNP:[0..3] Mol) (NNP:[4..13] Pharmacol) (.:[13..14] .) (CD:[15..19] 1997) (NNP:[20..23] Jul) (::[23..24] ;) (CD:[24..26] 52) (-LRB-:[26..27] -LRB-) (CD:[27..28] 1) (-RRB-:[28..29] -RRB-) (::[29..30] :) (CD:[30..32] 30) (::[32..33] -) (CD:[33..34] 7) (.:[34..35] .))) ;sentence 1 Span:41..186 ;Cytokine gene expression during ontogeny in murine thymus on activation of ;the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin. ;[121..146]:substance:"aryl hydrocarbon receptor" ;[150..185]:substance:"2,3,7,8-tetrachlorodibenzo-p-dioxin" (SENT (NP-HLN (NP (NN:[41..49] Cytokine) (NN:[50..54] gene) (NN:[55..65] expression)) (PP-TMP (IN:[66..72] during) (NP (NP (NN:[73..81] ontogeny)) (PP (IN:[82..84] in) (NP (JJ:[85..91] murine) (NN:[92..98] thymus))) (PP (IN:[99..101] on) (NP (NP (NN:[102..112] activation)) (PP (IN:[113..115] of) (NP (DT:[116..119] the) (NML (NN:[121..125] aryl) (NN:[126..137] hydrocarbon)) (NN:[138..146] receptor))) (PP (IN:[147..149] by) (NP (NN:[150..185] 2,3,7,8-tetrachlorodibenzo-p-dioxin))))))) (.:[185..186] .))) ;section 2 Span:190..233 ;Lai ZW, Hundeiker C, Gleichmann E, Esser C. (SEC (FRAG (NNP:[190..193] Lai) (NNP:[194..196] ZW) (,:[196..197] ,) (NNP:[198..207] Hundeiker) (NNP:[208..209] C) (,:[209..210] ,) (NNP:[211..221] Gleichmann) (NNP:[222..223] E) (,:[223..224] ,) (NNP:[225..230] Esser) (NNP:[231..232] C) (.:[232..233] .))) ;section 3 Span:237..331 ;Medical Institute of Environmental Hygiene, Heinrich-Heine-University of ;Dusseldorf, Germany. (SEC (FRAG (NNP:[237..244] Medical) (NNP:[245..254] Institute) (IN:[255..257] of) (NNP:[258..271] Environmental) (NNP:[272..279] Hygiene) (,:[279..280] ,) (NNP:[281..289] Heinrich) (HYPH:[289..290] -) (NNP:[290..295] Heine) (HYPH:[295..296] -) (NNP:[296..306] University) (IN:[307..309] of) (NNP:[311..321] Dusseldorf) (,:[321..322] ,) (NNP:[323..330] Germany) (.:[330..331] .))) ;sentence 4 Span:335..505 ;2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) binds and activates the aryl ;hydrocarbon receptor (Ah-R), an endogenous transcription factor that is ;expressed in the thymus. ;[335..370]:substance:"2,3,7,8-Tetrachlorodibenzo-p-dioxin" ;[372..376]:substance:"TCDD" ;[402..428]:substance:"aryl hydrocarbon receptor" ;[430..434]:substance:"Ah-R" ;[451..471]:substance:"transcription factor" (SENT (S (NP-SBJ (NP (NN:[335..370] 2,3,7,8-Tetrachlorodibenzo-p-dioxin)) (NP (-LRB-:[371..372] -LRB-) (NN:[372..376] TCDD) (-RRB-:[376..377] -RRB-))) (VP (VBZ:[378..383] binds) (CC:[384..387] and) (VBZ:[388..397] activates) (NP (NP (NP (DT:[398..401] the) (NML (NN:[402..406] aryl) (NN:[408..419] hydrocarbon)) (NN:[420..428] receptor)) (NP (-LRB-:[429..430] -LRB-) (NN:[430..434] Ah-R) (-RRB-:[434..435] -RRB-))) (,:[435..436] ,) (NP (NP (DT:[437..439] an) (JJ:[440..450] endogenous) (NN:[451..464] transcription) (NN:[465..471] factor)) (SBAR (WHNP-1 (WDT:[472..476] that)) (S (NP-SBJ-1 (-NONE-:[476..476] *T*)) (VP (VBZ:[477..479] is) (VP (VBN:[481..490] expressed) (NP-1 (-NONE-:[490..490] *)) (PP-LOC (IN:[491..493] in) (NP (DT:[494..497] the) (NN:[498..504] thymus)))))))))) (.:[504..505] .))) ;sentence 5 Span:506..589 ;TCDD exposure leads, among other effects, to thymus atrophy and ;immunosuppression. ;[506..510]:substance:"TCDD" (SENT (S (NP-SBJ (NN:[506..510] TCDD) (NN:[511..519] exposure)) (VP (VBZ:[520..525] leads) (,:[525..526] ,) (PP (IN:[527..532] among) (NP (JJ:[533..538] other) (NNS:[539..546] effects))) (,:[546..547] ,) (PP-CLR (TO:[548..550] to) (NP (NP (NN:[551..557] thymus) (NN:[559..566] atrophy)) (CC:[567..570] and) (NP (NN:[571..588] immunosuppression))))) (.:[588..589] .))) ;sentence 6 Span:590..896 ;We previously analyzed the interference of TCDD with differentiation ;processes in fetal thymus organ cultures and found that in the presence of ;TCDD, the proliferation rate of immature (CD4- CD8- and CD4- CD8+ HSA+) ;thymocytes is inhibited, whereas the maturation along the CD4/CD8 path is ;accelerated. ;[633..637]:substance:"TCDD" ;[736..740]:substance:"TCDD" (SENT (S (NP-SBJ (PRP:[590..592] We)) (ADVP-TMP (RB:[593..603] previously)) (VP (VP (VBD:[604..612] analyzed) (NP (NP (DT:[613..616] the) (NN:[617..629] interference)) (PP (IN:[630..632] of) (NP (NN:[633..637] TCDD)))) (PP (IN:[639..643] with) (NP (NN:[644..659] differentiation) (NNS:[660..669] processes))) (PP-LOC (IN:[670..672] in) (NP (JJ:[673..678] fetal) (NN:[679..685] thymus) (NN:[686..691] organ) (NNS:[692..700] cultures)))) (CC:[701..704] and) (VP (VBD:[705..710] found) (SBAR (IN:[711..715] that) (S (PP (IN:[716..718] in) (NP (NP (DT:[720..723] the) (NN:[724..732] presence)) (PP (IN:[733..735] of) (NP (NN:[736..740] TCDD))))) (,:[740..741] ,) (NP-SBJ-2 (NP (DT:[742..745] the) (NN:[746..759] proliferation) (NN:[760..764] rate)) (PP (IN:[765..767] of) (NP (ADJP (JJ:[768..776] immature) (PP (-LRB-:[777..778] -LRB-) (NP (NP (NN:[778..781] CD4) (SYM:[781..782] -)) (NP (NN:[783..786] CD8) (SYM:[786..787] -)) (CC:[788..791] and) (NP (NN:[792..795] CD4) (SYM:[795..796] -)) (NP (NN:[798..801] CD8) (SYM:[801..802] +)) (NP (NN:[803..806] HSA) (SYM:[806..807] +))) (-RRB-:[807..808] -RRB-))) (NNS:[809..819] thymocytes)))) (VP (VBZ:[820..822] is) (VP (VBN:[823..832] inhibited) (NP-2 (-NONE-:[832..832] *)) (,:[832..833] ,) (SBAR-ADV (IN:[834..841] whereas) (S (NP-SBJ-1 (NP (DT:[842..845] the) (NN:[846..856] maturation)) (PP (IN:[857..862] along) (NP (DT:[863..866] the) (NML (NN:[867..870] CD4) (SYM:[870..871] /) (NN:[871..874] CD8)) (NN:[876..880] path)))) (VP (VBZ:[881..883] is) (VP (VBN:[884..895] accelerated) (NP-1 (-NONE-:[895..895] *)))))))))))) (.:[895..896] .))) ;sentence 7 Span:897..1153 ;Moreover, the differentiation of thymocytes is skewed by TCDD at < or = 40% ;(compared with approximately 15% without TCDD) of the CD8 single-positive ;subset of future cytotoxic T cells, and apparently more cells audition for ;and pass positive selection. ;[955..959]:substance:"TCDD" ;[963..973]:quantitative-value:"< or = 40%" ;[989..1006]:quantitative-value:"approximately 15%" ;[1015..1019]:substance:"TCDD" (SENT (S (S (ADVP (RB:[897..905] Moreover)) (,:[905..906] ,) (NP-SBJ-4 (NP (DT:[907..910] the) (NN:[911..926] differentiation)) (PP (IN:[927..929] of) (NP (NNS:[930..940] thymocytes)))) (VP (VBZ:[941..943] is) (VP (VBN:[944..950] skewed) (NP-4 (-NONE-:[950..950] *)) (PP (IN:[951..953] by) (NP-LGS (NN:[955..959] TCDD))) (PP (IN:[960..962] at) (NP (NP (QP (SYM:[963..964] <) (CC:[965..967] or) (SYM:[968..969] =) (CD:[970..972] 40)) (NN:[972..973] %) (PRN (-LRB-:[974..975] -LRB-) (VP (VBN:[975..983] compared) (NP (-NONE-:[983..983] *)) (PP-CLR (IN:[984..988] with) (NP (NP (QP (RB:[989..1002] approximately) (CD:[1003..1005] 15)) (NN:[1005..1006] %)) (PP (IN:[1007..1014] without) (NP (NN:[1015..1019] TCDD)))))) (-RRB-:[1019..1020] -RRB-))) (PP (IN:[1021..1023] of) (NP (NP (DT:[1024..1027] the) (NN:[1028..1031] CD8) (ADJP (JJ:[1033..1039] single) (HYPH:[1039..1040] -) (JJ:[1040..1048] positive)) (NN:[1049..1055] subset)) (PP (IN:[1056..1058] of) (NP (JJ:[1059..1065] future) (JJ:[1066..1075] cytotoxic) (NN:[1076..1077] T) (NNS:[1078..1083] cells)))))))))) (,:[1083..1084] ,) (CC:[1085..1088] and) (S (ADVP (RB:[1089..1099] apparently)) (NP-SBJ (JJR:[1100..1104] more) (NNS:[1105..1110] cells)) (VP (VP (VBP:[1112..1120] audition) (PP-CLR (IN:[1121..1124] for) (NP-1 (-NONE-:[1124..1124] *RNR*)))) (CC:[1125..1128] and) (VP (VBP:[1129..1133] pass) (NP-1 (-NONE-:[1133..1133] *RNR*))) (NP-1 (JJ:[1134..1142] positive) (NN:[1143..1152] selection)))) (.:[1152..1153] .))) ;sentence 8 Span:1154..1320 ;The fetal murine thymus expresses functional Ah-R mRNA, as shown by reverse ;transcription-polymerase chain reaction and TCDD-inducible CYP1A1 and CYP1B1 ;expression. ;[1200..1209]:substance:"Ah-R mRNA" ;[1245..1255]:substance:"polymerase" ;[1276..1280]:substance:"TCDD" ;[1291..1297]:cyp450:"CYP1A1" ;[1302..1308]:cyp450:"CYP1B1" (SENT (S (NP-SBJ (DT:[1154..1157] The) (JJ:[1158..1163] fetal) (JJ:[1164..1170] murine) (NN:[1171..1177] thymus)) (VP (VBZ:[1178..1187] expresses) (NP (JJ:[1189..1199] functional) (NN:[1200..1204] Ah-R) (NN:[1205..1209] mRNA)) (,:[1209..1210] ,) (PP-MNR (IN:[1211..1213] as) (S-NOM (NP-SBJ-3 (-NONE-:[1213..1213] *)) (VP (VBN:[1214..1219] shown) (NP-3 (-NONE-:[1219..1219] *)) (PP (IN:[1220..1222] by) (NP-LGS (NP (NML (JJ:[1223..1230] reverse) (NN:[1231..1244] transcription)) (HYPH:[1244..1245] -) (NN:[1245..1255] polymerase) (NN:[1256..1261] chain) (NN:[1263..1271] reaction)) (CC:[1272..1275] and) (NP (NP (ADJP-1 (NN:[1276..1280] TCDD) (HYPH:[1280..1281] -) (JJ:[1281..1290] inducible)) (NN:[1291..1297] CYP1A1) (NML-2 (-NONE-:[1297..1297] *P*))) (CC:[1298..1301] and) (NP (ADJP-1 (-NONE-:[1301..1301] *P*)) (NN:[1302..1308] CYP1B1) (NML-2 (NN:[1309..1319] expression)))))))))) (.:[1319..1320] .))) ;sentence 9 Span:1321..1639 ;Because the differentiation of thymocytes is to a considerable extent ;controlled by cytokines and many cytokine genes are potential targets of the ;Ah-R due to Ah-R-binding elements (xenobiotic response elements) in their ;promoters, we analyzed the cytokine expression in fetal thymus organ culture ;exposed to TCDD. ;[1470..1474]:substance:"Ah-R" ;[1483..1487]:substance:"Ah-R" ;[1506..1516]:substance:"xenobiotic" ;[1545..1554]:substance:"promoters" ;[1634..1638]:substance:"TCDD" (SENT (S (SBAR-PRP (IN:[1321..1328] Because) (S (S (NP-SBJ-2 (NP (DT:[1329..1332] the) (NN:[1334..1349] differentiation)) (PP (IN:[1350..1352] of) (NP (NNS:[1353..1363] thymocytes)))) (VP (VBZ:[1364..1366] is) (VP (PP-EXT (TO:[1367..1369] to) (NP (DT:[1370..1371] a) (JJ:[1372..1384] considerable) (NN:[1385..1391] extent))) (VBN:[1392..1402] controlled) (NP-2 (-NONE-:[1402..1402] *)) (PP (IN:[1403..1405] by) (NP-LGS (NNS:[1407..1416] cytokines)))))) (CC:[1417..1420] and) (S (NP-SBJ (JJ:[1421..1425] many) (NN:[1426..1434] cytokine) (NNS:[1435..1440] genes)) (VP (VBP:[1441..1444] are) (NP-PRD (NP (JJ:[1445..1454] potential) (NNS:[1455..1462] targets)) (PP (IN:[1463..1465] of) (NP (DT:[1466..1469] the) (NN:[1470..1474] Ah-R))) (ADJP (IN:[1475..1478] due) (PP (TO:[1479..1481] to) (NP (NP (NP (ADJP (NN:[1483..1487] Ah-R) (HYPH:[1487..1488] -) (VBG:[1488..1495] binding)) (NNS:[1496..1504] elements)) (NP (-LRB-:[1505..1506] -LRB-) (JJ:[1506..1516] xenobiotic) (NN:[1517..1525] response) (NNS:[1526..1534] elements) (-RRB-:[1534..1535] -RRB-))) (PP-LOC (IN:[1536..1538] in) (NP (PRP$:[1539..1544] their) (NNS:[1545..1554] promoters))))))))))) (,:[1554..1555] ,) (NP-SBJ (PRP:[1556..1558] we)) (VP (VBD:[1560..1568] analyzed) (NP (DT:[1569..1572] the) (NN:[1573..1581] cytokine) (NN:[1582..1592] expression)) (PP-LOC (IN:[1593..1595] in) (NP (NP-1 (JJ:[1596..1601] fetal) (NN:[1602..1608] thymus) (NN:[1609..1614] organ) (NN:[1615..1622] culture)) (VP (VBN:[1623..1630] exposed) (NP-1 (-NONE-:[1630..1630] *)) (PP-CLR (TO:[1631..1633] to) (NP (NN:[1634..1638] TCDD))))))) (.:[1638..1639] .))) ;sentence 10 Span:1641..1792 ;Fetal thymi were cultured from gestation day 15 for < or = 8 days, thus ;covering ex vivo the period after population of the thymus anlage until ;birth. ;[1682..1685]:quantitative-units:"day" ;[1686..1688]:quantitative-value:"15" ;[1693..1701]:quantitative-value:"< or = 8" ;[1702..1706]:quantitative-units:"days" (SENT (S (NP-SBJ-2 (JJ:[1641..1646] Fetal) (NNS:[1647..1652] thymi)) (VP (VBD:[1653..1657] were) (VP (VBN:[1658..1666] cultured) (NP-2 (-NONE-:[1666..1666] *)) (PP-TMP (IN:[1667..1671] from) (NP (NN:[1672..1681] gestation) (NN:[1682..1685] day) (CD:[1686..1688] 15))) (PP-TMP (IN:[1689..1692] for) (NP (QP (SYM:[1693..1694] <) (CC:[1695..1697] or) (SYM:[1698..1699] =) (CD:[1700..1701] 8)) (NNS:[1702..1706] days))) (,:[1706..1707] ,) (S-MNR (NP-SBJ (-NONE-:[1707..1707] *)) (ADVP (RB:[1708..1712] thus)) (VP (VBG:[1713..1721] covering) (ADVP (FW:[1723..1725] ex) (FW:[1726..1730] vivo)) (NP-TMP (NP (DT:[1731..1734] the) (NN:[1735..1741] period)) (PP (IN:[1742..1747] after) (NP (NP (NN:[1748..1758] population)) (PP (IN:[1759..1761] of) (NP (DT:[1762..1765] the) (NN:[1766..1772] thymus) (NN:[1773..1779] anlage))))) (PP (IN:[1780..1785] until) (NP (NN:[1786..1791] birth)))))))) (.:[1791..1792] .))) ;sentence 11 Span:1793..2229 ;We show with semiquantitative reverse transcription-polymerase chain ;reaction that more interleukin (IL)-1beta, IL-2, IL-6, tumor growth factor ;(TGF)-beta3, and tumor necrosis factor-alpha are produced in TCDD-exposed ;thymi, whereas other cytokines (e.g., TGF-beta1, PAI-2, or IL-4) are only ;slightly up- and down-modulated during the culture period or not modulated ;at all (e.g., IL-1beta, IL-7, interferon-gamma, and TGF-beta2). ;[1846..1856]:substance:"polymerase" ;[1883..1905]:substance:"interleukin (IL)-1beta" ;[1907..1911]:substance:"IL-2" ;[1913..1917]:substance:"IL-6" ;[1919..1950]:substance:"tumor growth factor (TGF)-beta3" ;[1956..1984]:substance:"tumor necrosis factor-alpha" ;[2001..2005]:substance:"TCDD" ;[2036..2045]:substance:"cytokines" ;[2053..2062]:substance:"TGF-beta1" ;[2064..2069]:substance:"PAI-2" ;[2074..2078]:substance:"IL-4" ;[2180..2188]:substance:"IL-1beta" ;[2190..2194]:substance:"IL-7" ;[2196..2212]:substance:"interferon-gamma" ;[2218..2227]:substance:"TGF-beta2" (SENT (S (NP-SBJ (PRP:[1793..1795] We)) (VP (VBP:[1796..1800] show) (PP-MNR (IN:[1802..1806] with) (NP (JJ:[1807..1823] semiquantitative) (NML (JJ:[1824..1831] reverse) (NN:[1832..1845] transcription)) (HYPH:[1845..1846] -) (NN:[1846..1856] polymerase) (NN:[1857..1862] chain) (NN:[1863..1871] reaction))) (SBAR (IN:[1872..1876] that) (S (NP-SBJ-5 (NP (ADJP-4 (JJR:[1877..1881] more)) (NML (NML (NN:[1883..1894] interleukin)) (NML (-LRB-:[1895..1896] -LRB-) (NN:[1896..1898] IL) (-RRB-:[1898..1899] -RRB-))) (HYPH:[1899..1900] -) (NN:[1900..1905] 1beta)) (,:[1905..1906] ,) (NP (ADJP-4 (-NONE-:[1906..1906] *P*)) (NN:[1907..1911] IL-2)) (,:[1911..1912] ,) (NP (ADJP-4 (-NONE-:[1912..1912] *P*)) (NN:[1913..1917] IL-6)) (,:[1917..1918] ,) (NP (ADJP-4 (-NONE-:[1918..1918] *P*)) (NML (NML (NN:[1919..1924] tumor) (NN:[1925..1931] growth) (NN:[1932..1938] factor)) (NML (-LRB-:[1939..1940] -LRB-) (NN:[1940..1943] TGF) (-RRB-:[1943..1944] -RRB-))) (HYPH:[1944..1945] -) (NN:[1945..1950] beta3)) (,:[1950..1951] ,) (CC:[1952..1955] and) (NP (ADJP-4 (-NONE-:[1955..1955] *P*)) (NML (NN:[1956..1961] tumor) (NN:[1963..1971] necrosis)) (NN:[1972..1984] factor-alpha))) (VP (VBP:[1985..1988] are) (VP (VBN:[1989..1997] produced) (NP-5 (-NONE-:[1997..1997] *)) (PP-LOC (IN:[1998..2000] in) (NP (ADJP (NN:[2001..2005] TCDD) (HYPH:[2005..2006] -) (VBN:[2006..2013] exposed)) (NNS:[2014..2019] thymi)))) (,:[2019..2020] ,) (SBAR-ADV (IN:[2021..2028] whereas) (S (NP-SBJ-2 (JJ:[2029..2034] other) (NNS:[2036..2045] cytokines) (PRN (-LRB-:[2046..2047] -LRB-) (NP (ADVP (FW:[2047..2051] e.g.)) (,:[2051..2052] ,) (NN:[2053..2062] TGF-beta1) (,:[2062..2063] ,) (NN:[2064..2069] PAI-2) (,:[2069..2070] ,) (CC:[2071..2073] or) (NN:[2074..2078] IL-4)) (-RRB-:[2078..2079] -RRB-))) (VP (VBP:[2080..2083] are) (VP (VP (VP (ADVP (RB:[2084..2088] only) (RB:[2089..2097] slightly)) (VP (RB:[2098..2100] up) (HYPH:[2100..2101] -) (VP-1 (-NONE-:[2101..2101] *P*))) (CC:[2102..2105] and) (VP (RB:[2107..2111] down) (HYPH:[2111..2112] -) (VP-1 (VBN:[2112..2121] modulated)))) (PP-TMP (IN:[2122..2128] during) (NP (DT:[2129..2132] the) (NN:[2133..2140] culture) (NN:[2141..2147] period)))) (CC:[2148..2150] or) (VP (RB:[2151..2154] not) (VP (VBN:[2155..2164] modulated) (NP-2 (-NONE-:[2164..2164] *)) (PP (IN:[2165..2167] at) (NP (DT:[2168..2171] all))))) (PRN (-LRB-:[2172..2173] -LRB-) (NP (ADVP (FW:[2173..2177] e.g.)) (,:[2177..2178] ,) (NN:[2180..2188] IL-1beta) (,:[2188..2189] ,) (NN:[2190..2194] IL-7) (,:[2194..2195] ,) (NN:[2196..2212] interferon-gamma) (,:[2212..2213] ,) (CC:[2214..2217] and) (NN:[2218..2227] TGF-beta2)) (-RRB-:[2227..2228] -RRB-)))))))))) (.:[2228..2229] .))) ;section 12 Span:2233..2277 ;PMID: 9224809 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[2233..2237] PMID) (::[2237..2238] :) (CD:[2239..2246] 9224809) (NN:[2247..2248] -LSB-) (NNP:[2248..2254] PubMed) (::[2255..2256] -) (NN:[2257..2264] indexed) (IN:[2265..2268] for) (NNP:[2269..2276] MEDLINE) (-RRB-:[2276..2277] -RSB-)))