2005 Fiscal Year Final Research Report Summary
Study on the regulatory role of hypoxia sensor or hypoxia-inducible factor 1 system in inflammation
| Project/Area Number |
16591576
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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 | Kyoto University (2005)
Tazuke Kofukai Medical Research Institute (2004) |
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Principal Investigator |
HIROTA Kiichi Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (00283606)
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| Project Period (FY) |
2004 – 2005
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| Keywords | hypoxia / macrophage / differentiation / hypoxia sensor / inflammation / HIF-1 |
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| Research Abstract |
Monocytes/macrophages of the myeloid lineage are the main cellular effectors of innate immunity. Hypoxia inducible factor-1 (HIF-1) is essential for myeloid cell activation in response to inflammatory stimuli. However, it has not been established whether HIF-1 activity is induced during differentiation from monocyte to macrophage. We demonstrate that macrophage differentiation of THP-1 cells or monocytes from peripheral blood induces increased expression of both HIF-1a and HIF-1b as well as increased HIF-1 transcriptional activity leading to increased expression of HIF-1 target genes. The increased HIF-1 activity in differentiated THP-1 cells resulted from the combined effect of increased HIF-1a mRNA levels and increased HIF-1a protein synthesis. Differentiation-induced HIF-1a protein and mRNA and HIF-1-dependent gene expression was blocked by treating cells with an inhibitor of the protein kinase C or MAP kinase signaling pathway. We also demonstrate that lipopolysaccharide induces HIF-1 activation by enhancing both HIF-1a protein expression through a translation-dependent pathway and HIF-1a transcriptional activity in THP-1 cells that have undergone macrophage differentiation, but not in undifferentiated monocytic THP-1 cells, via a pathway that requires the generation of reactive oxygen species.
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[Journal Article] Activation of hypoxia-inducible factor 1 during macrophage differentiation2006
Author(s)
Oda, T., Hirota, K, Nishi, K., Takabuchi, S., Oda, S., Yamada, H., Arai, T., Fukuda, K., Kita, T., Adachi, T., et al.
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Journal Title
Am J Physiol Cell Physiol
Description
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[Journal Article] Opioid receptor stimulation does not affect cellular hypoxia-induced gene responses mediated by hypoxia-inducible factor 1 in cultured cell lines2005
Author(s)
Takabuchi, S., Hirota, K., Oda, S., Nishi, K., Oda, T., Shingu, K., Adachi, T., Fukuda, K
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Journal Title
J Anesth 19
Pages: 263-265
Description
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[Journal Article] The effect of local anesthetics on the cellular hypoxia-induced gene responses mediated by hypoxia-inducible factor 12005
Author(s)
Nishi, K., Hirota, K., Takabuchi, S., Oda, S., Fukuda, K., Adachi, T., Shingu, T
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Journal Title
Description
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[Journal Article] Synergistic effect of hypoxia and TNF-alpha on production of PAI-1 in human proximal renal tubular cells2005
Author(s)
Li, X., Kimura, H., Hirota, K., Kasuno, K., Torii, K., Okada, T., Kurooka, H., Yokota, Y., Yoshida, H
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Journal Title
Kidney Int 68
Pages: 569-583
Description
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[Journal Article] The intravenous anesthetic propofol inhibits hypoxia-inducible factor 1 activity in an oxygen tension-dependent manner2004
Author(s)
Takabuchi, S., Hirota, K., Nishi, K., Oda, S., Oda, T., Shingu, T., Takabayashi, A., Adachi, T., Semenza, G.L., Fukuda, K
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Journal Title
FEBS Lett 577
Pages: 434-438
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The inhibitory effect of sodium nitroprusside on HIF-1 activation is not dependent on nitric oxide-soluble guanylyl cyclase pathway2004
Author(s)
Takabuchi, S., Hirota, K., Nishi, K., Oda, S., Oda, T., Shingu, T., Takabayashi, A., Adachi, T., Semenza, G.L., Fukuda, K
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Journal Title
Biochem Biophys Res Commun 324
Pages: 417-423
Description
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[Journal Article] Nitric oxide induces hypoxia-inducible factor 1 activation that is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling2004
Author(s)
Kasuno, K., Takabuchi, S., Fukuda, K., Kizaka-Kondoh, S., Yodoi, J., Adachi, T., Semenza, G.L., Hirota, K
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Journal Title
J Biol Chem 279
Pages: 2550-2558
Description
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[Journal Article] Induction of hypoxia-inducible factor 1 activity by muscarinic acetylcholine receptor signaling2004
Author(s)
Hirota, K, Fukuda, R., Takabuchi, S., Kizaka-Kondoh, S., Adachi, T., Fukuda, K., Semenza, G.L
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Journal Title
J Biol Chem 279
Pages: 41521-41528
Description
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