| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-152 |
Sentence |
denotes |
The regulation of interleukin-8 by hypoxia in human macrophages--a potential role in the pathogenesis of the acute respiratory distress syndrome (ARDS). |
| T2 |
153-164 |
Sentence |
denotes |
BACKGROUND: |
| T3 |
165-272 |
Sentence |
denotes |
The acute respiratory distress syndrome (ARDS) represents a form of severe acute inflammatory lung disease. |
| T4 |
273-490 |
Sentence |
denotes |
We have previously demonstrated significantly raised interleukin-8 (IL-8) levels in the lungs of at-risk patients that progress to ARDS, and identified the alveolar macrophage as an important source of this chemokine. |
| T5 |
491-658 |
Sentence |
denotes |
We wished to extend this study in a well-defined group of patients with major trauma, and to investigate potential mechanisms for rapid intrapulmonary IL-8 generation. |
| T6 |
659-681 |
Sentence |
denotes |
MATERIALS AND METHODS: |
| T7 |
682-800 |
Sentence |
denotes |
Patients with major trauma underwent bronchoalveolar lavage (BAL) and IL-8 levels were measured in BAL fluid by ELISA. |
| T8 |
801-888 |
Sentence |
denotes |
Human macrophages were derived from peripheral blood monocytes from healthy volunteers. |
| T9 |
889-975 |
Sentence |
denotes |
Rabbit alveolar macrophages were obtained from ex-vivo lavage of healthy rabbit lungs. |
| T10 |
976-1052 |
Sentence |
denotes |
Macrophages were culture under normoxic or hypoxic (PO2 26 mmHg) conditions. |
| T11 |
1053-1183 |
Sentence |
denotes |
IL-8 and other proinflammatory mediator expression was measured by ELISA, northern blotting or multi-probe RNase protection assay. |
| T12 |
1184-1192 |
Sentence |
denotes |
RESULTS: |
| T13 |
1193-1350 |
Sentence |
denotes |
In patients with major trauma, IL-8 levels were significantly higher in patients that progressed to ARDS compared to those that did not (n = 56, P = 0.0001). |
| T14 |
1351-1428 |
Sentence |
denotes |
High IL-8 levels negatively correlated with PaO2/FiO2 (r = -0.56, P < 0.001). |
| T15 |
1429-1562 |
Sentence |
denotes |
In human monocyte derived macrophages hypoxia rapidly upregulated IL-8 protein (within 2 hours) and mRNA expression (within 30 mins). |
| T16 |
1563-1635 |
Sentence |
denotes |
Acute hypoxia also increased rabbit alveolar macrophage IL-8 expression. |
| T17 |
1636-1711 |
Sentence |
denotes |
Hypoxia increased DNA binding activity of AP-1 and C/EBP but not NF-kappaB. |
| T18 |
1712-1822 |
Sentence |
denotes |
Hypoxia induced HIF-1 expression, but cobaltous ions and desferrioxamine did not mimic hypoxic IL-8 induction. |
| T19 |
1823-1919 |
Sentence |
denotes |
Hypoxia downregulated a range of other proinflammatory mediators, including MCP-1 and TNF-alpha. |
| T20 |
1920-2049 |
Sentence |
denotes |
Both the pattern of cytokine expression and transcription factor activation by hypoxia was different to that seen with endotoxin. |
| T21 |
2050-2062 |
Sentence |
denotes |
CONCLUSIONS: |
| T22 |
2063-2172 |
Sentence |
denotes |
Rapidly raised intrapulmonary IL-8 levels are associated with ARDS progression in patients with major trauma. |
| T23 |
2173-2343 |
Sentence |
denotes |
Acute hypoxia, a clinically relevant stimulus, rapidly and selectively upregulates IL-8 in macrophages associated with a novel pattern of transcription factor activation. |
| T24 |
2344-2504 |
Sentence |
denotes |
Acute hypoxia may represent one of potentially several proinflammatory stimuli responsible for rapid intrapulmonary IL-8 generation in patients at-risk of ARDS. |
| T1 |
0-152 |
Sentence |
denotes |
The regulation of interleukin-8 by hypoxia in human macrophages--a potential role in the pathogenesis of the acute respiratory distress syndrome (ARDS). |
| T2 |
153-164 |
Sentence |
denotes |
BACKGROUND: |
| T3 |
165-272 |
Sentence |
denotes |
The acute respiratory distress syndrome (ARDS) represents a form of severe acute inflammatory lung disease. |
| T4 |
273-490 |
Sentence |
denotes |
We have previously demonstrated significantly raised interleukin-8 (IL-8) levels in the lungs of at-risk patients that progress to ARDS, and identified the alveolar macrophage as an important source of this chemokine. |
| T5 |
491-658 |
Sentence |
denotes |
We wished to extend this study in a well-defined group of patients with major trauma, and to investigate potential mechanisms for rapid intrapulmonary IL-8 generation. |
| T6 |
659-681 |
Sentence |
denotes |
MATERIALS AND METHODS: |
| T7 |
682-800 |
Sentence |
denotes |
Patients with major trauma underwent bronchoalveolar lavage (BAL) and IL-8 levels were measured in BAL fluid by ELISA. |
| T8 |
801-888 |
Sentence |
denotes |
Human macrophages were derived from peripheral blood monocytes from healthy volunteers. |
| T9 |
889-975 |
Sentence |
denotes |
Rabbit alveolar macrophages were obtained from ex-vivo lavage of healthy rabbit lungs. |
| T10 |
976-1052 |
Sentence |
denotes |
Macrophages were culture under normoxic or hypoxic (PO2 26 mmHg) conditions. |
| T11 |
1053-1183 |
Sentence |
denotes |
IL-8 and other proinflammatory mediator expression was measured by ELISA, northern blotting or multi-probe RNase protection assay. |
| T12 |
1184-1192 |
Sentence |
denotes |
RESULTS: |
| T13 |
1193-1350 |
Sentence |
denotes |
In patients with major trauma, IL-8 levels were significantly higher in patients that progressed to ARDS compared to those that did not (n = 56, P = 0.0001). |
| T14 |
1351-1428 |
Sentence |
denotes |
High IL-8 levels negatively correlated with PaO2/FiO2 (r = -0.56, P < 0.001). |
| T15 |
1429-1562 |
Sentence |
denotes |
In human monocyte derived macrophages hypoxia rapidly upregulated IL-8 protein (within 2 hours) and mRNA expression (within 30 mins). |
| T16 |
1563-1635 |
Sentence |
denotes |
Acute hypoxia also increased rabbit alveolar macrophage IL-8 expression. |
| T17 |
1636-1711 |
Sentence |
denotes |
Hypoxia increased DNA binding activity of AP-1 and C/EBP but not NF-kappaB. |
| T18 |
1712-1822 |
Sentence |
denotes |
Hypoxia induced HIF-1 expression, but cobaltous ions and desferrioxamine did not mimic hypoxic IL-8 induction. |
| T19 |
1823-1919 |
Sentence |
denotes |
Hypoxia downregulated a range of other proinflammatory mediators, including MCP-1 and TNF-alpha. |
| T20 |
1920-2049 |
Sentence |
denotes |
Both the pattern of cytokine expression and transcription factor activation by hypoxia was different to that seen with endotoxin. |
| T21 |
2050-2062 |
Sentence |
denotes |
CONCLUSIONS: |
| T22 |
2063-2172 |
Sentence |
denotes |
Rapidly raised intrapulmonary IL-8 levels are associated with ARDS progression in patients with major trauma. |
| T23 |
2173-2343 |
Sentence |
denotes |
Acute hypoxia, a clinically relevant stimulus, rapidly and selectively upregulates IL-8 in macrophages associated with a novel pattern of transcription factor activation. |
| T24 |
2344-2504 |
Sentence |
denotes |
Acute hypoxia may represent one of potentially several proinflammatory stimuli responsible for rapid intrapulmonary IL-8 generation in patients at-risk of ARDS. |