| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-242 |
Sentence |
denotes |
Responses to the proinflammatory cytokines interleukin-1 and tumor necrosis factor alpha in cells derived from rheumatoid synovium and other joint tissues involve nuclear factor kappaB-mediated induction of the Ets transcription factor ESE-1. |
| T2 |
243-253 |
Sentence |
denotes |
OBJECTIVE: |
| T3 |
254-559 |
Sentence |
denotes |
To investigate the expression of the novel Ets transcription factor ESE-1 in rheumatoid synovium and in cells derived from joint tissues, and to analyze the role of nuclear factor kappaB (NF-kappaB) as one of the central downstream targets in mediating the induction of ESE-1 by proinflammatory cytokines. |
| T4 |
560-737 |
Sentence |
denotes |
METHODS: ESE-1 protein expression was analyzed by immunohistochemistry using antibodies in synovial tissues from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). |
| T5 |
738-1169 |
Sentence |
denotes |
ESE-1 messenger RNA (mRNA) levels were analyzed by reverse transcriptase-polymerase chain reaction or Northern blotting in human chondrocytes, synovial fibroblasts, osteoblasts, and macrophages, before and after exposure to interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha), or lipopolysaccharide (LPS) with or without prior infection with an adenovirus encoding the inhibitor of nuclear factor kappaB (IkappaB). |
| T6 |
1170-1338 |
Sentence |
denotes |
The wild-type ESE-1 promoter and the ESE-1 promoter mutated in the NF-kappaB site were cloned into a luciferase reporter vector and analyzed in transient transfections. |
| T7 |
1339-1538 |
Sentence |
denotes |
Electrophoretic mobility shift assays (EMSAs) and supershift assays with antibodies against members of the NF-kappaB family were conducted using the NF-kappaB site from the ESE-1 promoter as a probe. |
| T8 |
1539-1547 |
Sentence |
denotes |
RESULTS: |
| T9 |
1548-1727 |
Sentence |
denotes |
Immunohistochemical analysis showed specific expression of ESE-1 in cells of the synovial lining layer and in some mononuclear and endothelial cells in RA and OA synovial tissues. |
| T10 |
1728-1872 |
Sentence |
denotes |
ESE-1 mRNA expression could be induced by IL-1beta and TNFalpha in cells such as synovial fibroblasts, chondrocytes, osteoblasts, and monocytes. |
| T11 |
1873-2096 |
Sentence |
denotes |
Transient transfection experiments and EMSAs showed that induction of ESE-1 gene expression by IL-1beta requires activation of NF-kappaB and binding of p50 and p65 family members to the NF-kappaB site in the ESE-1 promoter. |
| T12 |
2097-2197 |
Sentence |
denotes |
Overexpression of IkappaB using an adenoviral vector blocked IL-1beta-induced ESE-1 mRNA expression. |
| T13 |
2198-2297 |
Sentence |
denotes |
Chromatin immunoprecipitation further confirmed that NF-kappaB binds to the ESE-1 promoter in vivo. |
| T14 |
2298-2524 |
Sentence |
denotes |
CONCLUSION: ESE-1 is expressed in synovial tissues in RA and, to a variable extent, in OA, and is specifically induced in synovial fibroblasts, chondrocytes, osteoblasts, and monocyte/macrophages by IL-1beta, TNFalpha, or LPS. |
| T15 |
2525-2712 |
Sentence |
denotes |
This induction relies on the translocation of the NF-kappaB family members p50 and p65 to the nucleus and transactivation of the ESE-1 promoter via a high-affinity NF-kappaB binding site. |
| T16 |
2713-2822 |
Sentence |
denotes |
ESE-1 may play a role in mediating some effects of proinflammatory stimuli in cells at sites of inflammation. |
| T1 |
0-242 |
Sentence |
denotes |
Responses to the proinflammatory cytokines interleukin-1 and tumor necrosis factor alpha in cells derived from rheumatoid synovium and other joint tissues involve nuclear factor kappaB-mediated induction of the Ets transcription factor ESE-1. |
| T2 |
243-253 |
Sentence |
denotes |
OBJECTIVE: |
| T3 |
254-559 |
Sentence |
denotes |
To investigate the expression of the novel Ets transcription factor ESE-1 in rheumatoid synovium and in cells derived from joint tissues, and to analyze the role of nuclear factor kappaB (NF-kappaB) as one of the central downstream targets in mediating the induction of ESE-1 by proinflammatory cytokines. |
| T4 |
560-737 |
Sentence |
denotes |
METHODS: ESE-1 protein expression was analyzed by immunohistochemistry using antibodies in synovial tissues from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). |
| T5 |
738-1169 |
Sentence |
denotes |
ESE-1 messenger RNA (mRNA) levels were analyzed by reverse transcriptase-polymerase chain reaction or Northern blotting in human chondrocytes, synovial fibroblasts, osteoblasts, and macrophages, before and after exposure to interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha), or lipopolysaccharide (LPS) with or without prior infection with an adenovirus encoding the inhibitor of nuclear factor kappaB (IkappaB). |
| T6 |
1170-1338 |
Sentence |
denotes |
The wild-type ESE-1 promoter and the ESE-1 promoter mutated in the NF-kappaB site were cloned into a luciferase reporter vector and analyzed in transient transfections. |
| T7 |
1339-1538 |
Sentence |
denotes |
Electrophoretic mobility shift assays (EMSAs) and supershift assays with antibodies against members of the NF-kappaB family were conducted using the NF-kappaB site from the ESE-1 promoter as a probe. |
| T8 |
1539-1547 |
Sentence |
denotes |
RESULTS: |
| T9 |
1548-1727 |
Sentence |
denotes |
Immunohistochemical analysis showed specific expression of ESE-1 in cells of the synovial lining layer and in some mononuclear and endothelial cells in RA and OA synovial tissues. |
| T10 |
1728-1872 |
Sentence |
denotes |
ESE-1 mRNA expression could be induced by IL-1beta and TNFalpha in cells such as synovial fibroblasts, chondrocytes, osteoblasts, and monocytes. |
| T11 |
1873-2096 |
Sentence |
denotes |
Transient transfection experiments and EMSAs showed that induction of ESE-1 gene expression by IL-1beta requires activation of NF-kappaB and binding of p50 and p65 family members to the NF-kappaB site in the ESE-1 promoter. |
| T12 |
2097-2197 |
Sentence |
denotes |
Overexpression of IkappaB using an adenoviral vector blocked IL-1beta-induced ESE-1 mRNA expression. |
| T13 |
2198-2297 |
Sentence |
denotes |
Chromatin immunoprecipitation further confirmed that NF-kappaB binds to the ESE-1 promoter in vivo. |
| T14 |
2298-2524 |
Sentence |
denotes |
CONCLUSION: ESE-1 is expressed in synovial tissues in RA and, to a variable extent, in OA, and is specifically induced in synovial fibroblasts, chondrocytes, osteoblasts, and monocyte/macrophages by IL-1beta, TNFalpha, or LPS. |
| T15 |
2525-2712 |
Sentence |
denotes |
This induction relies on the translocation of the NF-kappaB family members p50 and p65 to the nucleus and transactivation of the ESE-1 promoter via a high-affinity NF-kappaB binding site. |
| T16 |
2713-2822 |
Sentence |
denotes |
ESE-1 may play a role in mediating some effects of proinflammatory stimuli in cells at sites of inflammation. |