Pathophysiological Response to Hypoxia-From the Molecular Mechanisms of Malady to Drug Discovery : Inflammatory Responses of Hypoxia-Inducible Factor 1α (HIF-1α) in T Cells Observed in Development of Vascular Remodeling

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Author(s)

    • FUKUHARA Yayoi
    • Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School
    • IMAMURA Yuko
    • Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School
    • ISHIZAWA Keisuke
    • Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School
    • IKEDA Yasumasa
    • Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School
    • TSUCHIYA Koichiro
    • Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School
    • TAMAKI Toshiaki
    • Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School

Abstract

Recent studies have shown that the cellular immune response to the hypoxic microenvironment constructed by vascular remodeling development modulates the resulting pathologic alterations. A major mechanism mediating adaptive responses to reduced oxygen availability is the regulation of transcription by hypoxia-inducible factor 1 (HIF-1). Impairment of HIF-1–dependent inflammatory responses in T cells causes an augmented vascular remodeling induced by arterial injury, which is shown as prominent neointimal hyperplasia and increase in infiltration of inflammatory cells at the adventitia in mice lacking Hif-1<I>α</I> specifically in T cells. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice have shown enhanced production of cytokines in activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice. This minireview shows that HIF-1<I>α</I> in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of the T cell–mediated immune response and suggests potential new therapeutic strategies that target HIF-1<I>α</I>.

Journal

  • Journal of Pharmacological Sciences

    Journal of Pharmacological Sciences 115(4), 433-439, 2011-04-20

    The Japanese Pharmacological Society

References:  80

Codes

  • NII Article ID (NAID)
    10029893030
  • NII NACSIS-CAT ID (NCID)
    AA11806667
  • Text Lang
    ENG
  • Article Type
    REV
  • ISSN
    13478613
  • NDL Article ID
    11049110
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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