title: 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.
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-1α 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-1α 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-1α.
authors.affiliation: Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan. tomita@basic.med.tokushima-u.ac.jp
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tomita
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kihira
authors.forename: Masaki
authors.initials: M
authors.lastname: Imanishi
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Fukuhara
authors.forename: Yuko
authors.initials: Y
authors.lastname: Imamura
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tamaki
mesh_terms: D000818:Animals; D055808:Drug Discovery; D006801:Humans; D000860:Hypoxia / Q000276:immunology* / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D007111:Immunity, Cellular / Q000502:physiology*; D015427:Reperfusion Injury / Q000276:immunology* / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D014657:Vasculitis / Q000276:immunology / Q000503:physiopathology
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit