0	18	Lipopolysaccharide	Lipopolysaccharide	NNP
19	28	induction	induction	NN
29	31	of	of	IN
32	35	the	the	DT
36	41	tumor	tumor	NN
42	50	necrosis	necrosis	NN
51	63	factor-alpha	factor-alpha	NN
64	72	promoter	promoter	NN
73	75	in	in	IN
76	81	human	human	JJ
82	91	monocytic	monocytic	JJ
92	97	cells	cell	NNS
97	98	.	.	.

99	109	Regulation	Regulation	NNP
110	112	by	by	IN
113	118	Egr-1	Egr-1	NNP
118	119	,	,	,
120	125	c-Jun	c-jun	NN
125	126	,	,	,
127	130	and	and	CC
131	140	NF-kappaB	NF-kappaB	NNP
141	154	transcription	transcription	NN
155	162	factors	factor	NNS
162	163	.	.	.

165	177	Biosynthesis	biosynthesis	NN
178	180	of	of	IN
181	186	tumor	tumor	NN
187	195	necrosis	necrosis	NN
196	208	factor-alpha	factor-alpha	NN
209	210	(	(	(
210	219	TNF-alpha	TNF-alpha	NNP
219	220	)	)	)
221	223	is	be	VBZ
224	237	predominantly	predominantly	RB
238	240	by	by	IN
241	246	cells	cell	NNS
247	249	of	of	IN
250	253	the	the	DT
254	263	monocytic	monocytic	JJ
264	271	lineage	lineage	NN
271	272	.	.	.

273	277	This	this	DT
278	283	study	study	NN
284	292	examined	examine	VBD
293	296	the	the	DT
297	301	role	role	NN
302	304	of	of	IN
305	312	various	various	JJ
313	323	cis-acting	cis-acting	JJ
324	334	regulatory	regulatory	JJ
335	343	elements	element	NNS
344	346	in	in	IN
347	350	the	the	DT
351	369	lipopolysaccharide	lipopolysaccharide	NN
370	371	(	(	(
371	374	LPS	LPS	NNP
374	375	)	)	)
376	385	induction	induction	NN
386	388	of	of	IN
389	392	the	the	DT
393	398	human	human	JJ
399	408	TNF-alpha	TNF-alpha	NNP
409	417	promoter	promoter	NN
418	420	in	in	IN
421	426	cells	cell	NNS
427	429	of	of	IN
430	439	monocytic	monocytic	JJ
440	447	lineage	lineage	NN
447	448	.	.	.

449	459	Functional	functional	JJ
460	468	analysis	analysis	NN
469	471	of	of	IN
472	481	monocytic	monocytic	JJ
482	487	THP-1	thp-1	NN
488	493	cells	cell	NNS
494	505	transfected	transfecte	VBN
506	510	with	with	IN
511	519	plasmids	plasmid	NNS
520	530	containing	contain	VBG
531	538	various	various	JJ
539	546	lengths	length	NNS
547	549	of	of	IN
550	559	TNF-alpha	TNF-alpha	NNP
560	568	promoter	promoter	NN
569	578	localized	localize	VBD
579	587	enhancer	enhancer	NN
588	596	elements	element	NNS
597	599	in	in	IN
600	601	a	a	DT
602	608	region	region	NN
609	610	(	(	(
610	614	-182	-182	CD
615	617	to	to	TO
618	621	-37	-37	CD
622	626	base	base	NN
627	632	pairs	pair	NNS
633	634	(	(	(
634	636	bp	bp	NN
636	637	)	)	)
637	638	)	)	)
639	643	that	that	WDT
644	648	were	be	VBD
649	657	required	require	VBN
658	661	for	for	IN
662	669	optimal	optimal	JJ
670	683	transcription	transcription	NN
684	686	of	of	IN
687	690	the	the	DT
691	700	TNF-alpha	TNF-alpha	NNP
701	705	gene	gene	NN
706	708	in	in	IN
709	717	response	response	NN
718	720	to	to	TO
721	724	LPS	LPS	NNP
724	725	.	.	.

726	729	Two	two	CD
730	737	regions	region	NNS
738	742	were	be	VBD
743	753	identified	identify	VBN
753	754	:	:	:
755	761	region	region	NN
762	763	I	i	CD
764	765	(	(	(
765	769	-182	-182	CD
770	772	to	to	TO
773	777	-162	-162	CD
778	780	bp	bp	NN
780	781	)	)	)
782	791	contained	contain	VBD
792	794	an	an	DT
795	806	overlapping	overlap	VBG
807	816	Sp1/Egr-1	sp1/egr-1	NN
817	821	site	site	NN
821	822	,	,	,
823	826	and	and	CC
827	833	region	region	NN
834	836	II	ii	CD
837	838	(	(	(
838	842	-119	-119	CD
843	845	to	to	TO
846	849	-88	-88	CD
849	850	)	)	)
851	860	contained	contain	VBD
861	864	CRE	CRE	NNP
865	868	and	and	CC
869	878	NF-kappaB	NF-kappaB	NNP
879	880	(	(	(
880	890	designated	designate	VBN
891	898	kappaB3	kappab3	NN
898	899	)	)	)
900	905	sites	site	NNS
905	906	.	.	.

907	909	In	in	IN
910	922	unstimulated	unstimulated	JJ
923	928	THP-1	thp-1	NN
928	929	,	,	,
930	941	CRE-binding	cre-binding	JJ
942	949	protein	protein	NN
950	953	and	and	CC
953	954	,	,	,
955	957	to	to	TO
958	959	a	a	DT
960	966	lesser	less	JJR
967	973	extent	extent	NN
973	974	,	,	,
975	980	c-Jun	c-jun	NN
981	990	complexes	complex	NNS
991	995	were	be	VBD
996	1001	found	find	VBN
1002	1004	to	to	TO
1005	1009	bind	bind	VB
1010	1012	to	to	TO
1013	1016	the	the	DT
1017	1020	CRE	CRE	NNP
1021	1025	site	site	NN
1025	1026	.	.	.

1027	1030	LPS	LPS	NNP
1031	1042	stimulation	stimulation	NN
1043	1052	increased	increase	VBD
1053	1056	the	the	DT
1057	1064	binding	binding	NN
1065	1067	of	of	IN
1068	1084	c-Jun-containing	c-jun-containing	JJ
1085	1094	complexes	complex	NNS
1094	1095	.	.	.

1096	1098	In	in	IN
1099	1107	addition	addition	NN
1107	1108	,	,	,
1109	1112	LPS	LPS	NNP
1113	1124	stimulation	stimulation	NN
1125	1132	induced	induce	VBD
1133	1136	the	the	DT
1137	1144	binding	binding	NN
1145	1147	of	of	IN
1148	1155	cognate	cognate	JJ
1156	1163	nuclear	nuclear	JJ
1164	1171	factors	factor	NNS
1172	1174	to	to	TO
1175	1178	the	the	DT
1179	1184	Egr-1	egr-1	NN
1185	1188	and	and	CC
1189	1196	kappaB3	kappab3	NN
1197	1202	sites	site	NNS
1202	1203	,	,	,
1204	1209	which	which	WDT
1210	1214	were	be	VBD
1215	1225	identified	identify	VBN
1226	1228	as	as	IN
1229	1234	Egr-1	egr-1	NN
1235	1238	and	and	CC
1239	1246	p50/p65	p50/p65	NN
1246	1247	,	,	,
1248	1260	respectively	respectively	RB
1260	1261	.	.	.

1262	1265	The	the	DT
1266	1269	CRE	CRE	NNP
1270	1273	and	and	CC
1274	1281	kappaB3	kappab3	NN
1282	1287	sites	site	NNS
1288	1290	in	in	IN
1291	1297	region	region	NN
1298	1300	II	ii	CD
1301	1309	together	together	RB
1310	1319	conferred	confer	VBD
1320	1326	strong	strong	JJ
1327	1330	LPS	lps	NN
1331	1345	responsiveness	responsiveness	NN
1346	1348	to	to	TO
1349	1350	a	a	DT
1351	1363	heterologous	heterologous	JJ
1364	1372	promoter	promoter	NN
1372	1373	,	,	,
1374	1381	whereas	whereas	IN
1382	1394	individually	individually	RB
1395	1399	they	they	PRP
1400	1406	failed	fail	VBD
1407	1409	to	to	TO
1410	1417	provide	provide	VB
1418	1433	transcriptional	transcriptional	JJ
1434	1444	activation	activation	NN
1444	1445	.	.	.

1446	1457	Furthermore	furthermore	RB
1457	1458	,	,	,
1459	1469	increasing	increase	VBG
1470	1473	the	the	DT
1474	1481	spacing	spacing	NN
1482	1489	between	between	IN
1490	1493	the	the	DT
1494	1497	CRE	CRE	NNP
1498	1501	and	and	CC
1502	1505	the	the	DT
1506	1513	kappaB3	kappab3	NN
1514	1519	sites	site	NNS
1520	1530	completely	completely	RB
1531	1540	abolished	abolish	VBD
1541	1544	LPS	LPS	NNP
1545	1554	induction	induction	NN
1554	1555	,	,	,
1556	1566	suggesting	suggest	VBG
1567	1568	a	a	DT
1569	1580	cooperative	cooperative	JJ
1581	1592	interaction	interaction	NN
1593	1600	between	between	IN
1601	1606	c-Jun	c-jun	NN
1607	1616	complexes	complex	NNS
1617	1620	and	and	CC
1621	1628	p50/p65	p50/p65	NN
1628	1629	.	.	.

1630	1635	These	these	DT
1636	1643	studies	study	NNS
1644	1652	indicate	indicate	VBP
1653	1657	that	that	IN
1658	1665	maximal	maximal	JJ
1666	1669	LPS	lps	NN
1670	1679	induction	induction	NN
1680	1682	of	of	IN
1683	1686	the	the	DT
1687	1696	TNF-alpha	TNF-alpha	NNP
1697	1705	promoter	promoter	NN
1706	1708	is	be	VBZ
1709	1717	mediated	mediate	VBN
1718	1720	by	by	IN
1721	1730	concerted	concerted	JJ
1731	1744	participation	participation	NN
1745	1747	of	of	IN
1748	1750	at	at	IN
1751	1756	least	least	JJS
1757	1760	two	two	CD
1761	1769	separate	separate	JJ
1770	1780	cis-acting	cis-acting	JJ
1781	1791	regulatory	regulatory	JJ
1792	1800	elements	element	NNS
1800	1801	.	.	.