| Project/Area Number |
15591629
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Kobe University |
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Principal Investigator |
NISHINA Kahoru Kobe University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (20311780)
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| Co-Investigator(Kenkyū-buntansha) |
MIKAWA Katsuya Kobe University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (40229662)
MORIKAWA Osamu Kobe University, University Hospital, Instructor, 医学部附属病院, 助手 (50335436)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Acute lung injury / Apoptosis / Artificial Ventilation / Alveolar epithelial cells / Mechanical Stress / Endotoxin / Neutrophils / Cytokines |
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| Research Abstract |
Ventilation is known to cause acute lung injury (ALI) in animals and often worsens lung damages in human ALI (ventilator-induced lung injury [VILI]). Many inflammatory cytokines released from alveolar epithelial type II cells (AEC-II) and apoptosis of AEC-II are thought to play an important role in the pathogenesis of VILI. We first investigated the effects of mechanical stretch on production of chemokine from AEC-II. Mechanical stress on rat cultured AEC-II per se did not stimulate release of GRO/CINC-1 but increased endotoxin-induced production of GRO/CINC-1. Secondly, we examined the effects of hypercapnic acidosis on chemokine production from AEC-II and apoptosis of the pneumocytes. Hypercapnia in the culture medium (PCO2 : 70-80mmHg) stimulated A549 cells, human AEC-II, IL-8 production as assessed by ELISA. IL-8 production was increased by inducing mRNA expression. Hypercapnic acidosis also multiplied endotoxin-induced IL-8 production. These data suggest that hypercapnic acidosis up-regulates inflammatory cytokines at the transcriptional level. Finally, we evaluated whether hypercapnia can change apoptosis of AEC-II. Hypercapnic acidosis per se slightly induced apoptosis of A549 cells (as assessed by APOPercentage Apoptosis Kit) although not significantly. Hypercapnic acidosis had no effect on apoptosis of A549 cells induced by hydrogen peroxide. These findings suggest that low tidal ventilation does not induce or potentiate apoptosis of AEC-II
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