Hypoxia-inducible factor-1α suppresses the expression of macrophage scavenger receptor 1

Ken Shirato, Takako Kizaki, Takuya Sakurai, Jun Etsu Ogasawara, Yoshinaga Ishibashi, Takehiko Iijima, Chikako Okada, Izumi Noguchi, Kazuhiko Imaizumi, Naoyuki Taniguchi, Hideki Ohno

    Research output: Contribution to journalArticle

    24 Citations (Scopus)

    Abstract

    Macrophages are distributed in all peripheral tissues and play a critical role in the first line of the innate immune defenses against bacterial infection by phagocytosis of bacterial pathogens through the macrophage scavenger receptor 1 (MSR1). Within tissues, the partial pressure of oxygen (pO 2) decreases depending on the distance of cells from the closest O2-supplying blood vessel. However, it is not clear how the expression of MSR1 in macrophages is regulated by low pO2. On the other hand, hypoxia-inducible factor (HIF)-1α is well known to control hypoxic responses through regulation of hypoxia-inducible genes. Therefore, we investigated the effects of hypoxia and HIF-1α on MSR1 expression and function in the macrophage cell line RAW264. Exposure to 1% O2 or treatment with the hypoxia-mimetic agent cobalt chloride (CoCl2) significantly suppressed the expression of MSR1 mRNA, accompanied by a markedly increase in levels of nuclear HIF-1α protein. The overexpression of HIF-1α in RAW264 cells suppressed the expression of MSR1 mRNA and protein, transcriptional activity of the MSR1 gene, and phagocytic capacity against the Gram-positive bacteria Listeria monocytogenes. The suppression of MSRl mRNA by hypoxia or C0Cl2 was inhibited by YC-1, an inhibitor of HF-1α, or by the depletion of HIF-1α expression by small interference RNA. These results indicate that hypoxia transcriptionally suppresses MSR1 expression through HF-1α.

    Original languageEnglish
    Pages (from-to)93-103
    Number of pages11
    JournalPflugers Archiv European Journal of Physiology
    Volume459
    Issue number1
    DOIs
    Publication statusPublished - 2009 Nov

    Fingerprint

    Hypoxia-Inducible Factor 1
    Scavenger Receptors
    Macrophages
    Messenger RNA
    Genes
    Tissue
    Listeria
    Partial Pressure
    Blood vessels
    Listeria monocytogenes
    Gram-Positive Bacteria
    Pathogens
    RNA Interference
    Phagocytosis
    Bacterial Infections
    Partial pressure
    Blood Vessels
    Bacteria
    Proteins
    Cells

    Keywords

    • Hypoxia hypoxia-inducible factor-1α
    • Macrophage
    • Macrophage scavenger receptor 1
    • Phagocytosis

    ASJC Scopus subject areas

    • Physiology
    • Clinical Biochemistry
    • Physiology (medical)
    • Medicine(all)

    Cite this

    Shirato, K., Kizaki, T., Sakurai, T., Ogasawara, J. E., Ishibashi, Y., Iijima, T., ... Ohno, H. (2009). Hypoxia-inducible factor-1α suppresses the expression of macrophage scavenger receptor 1. Pflugers Archiv European Journal of Physiology, 459(1), 93-103. https://doi.org/10.1007/s00424-009-0702-y

    Hypoxia-inducible factor-1α suppresses the expression of macrophage scavenger receptor 1. / Shirato, Ken; Kizaki, Takako; Sakurai, Takuya; Ogasawara, Jun Etsu; Ishibashi, Yoshinaga; Iijima, Takehiko; Okada, Chikako; Noguchi, Izumi; Imaizumi, Kazuhiko; Taniguchi, Naoyuki; Ohno, Hideki.

    In: Pflugers Archiv European Journal of Physiology, Vol. 459, No. 1, 11.2009, p. 93-103.

    Research output: Contribution to journalArticle

    Shirato, K, Kizaki, T, Sakurai, T, Ogasawara, JE, Ishibashi, Y, Iijima, T, Okada, C, Noguchi, I, Imaizumi, K, Taniguchi, N & Ohno, H 2009, 'Hypoxia-inducible factor-1α suppresses the expression of macrophage scavenger receptor 1', Pflugers Archiv European Journal of Physiology, vol. 459, no. 1, pp. 93-103. https://doi.org/10.1007/s00424-009-0702-y
    Shirato, Ken ; Kizaki, Takako ; Sakurai, Takuya ; Ogasawara, Jun Etsu ; Ishibashi, Yoshinaga ; Iijima, Takehiko ; Okada, Chikako ; Noguchi, Izumi ; Imaizumi, Kazuhiko ; Taniguchi, Naoyuki ; Ohno, Hideki. / Hypoxia-inducible factor-1α suppresses the expression of macrophage scavenger receptor 1. In: Pflugers Archiv European Journal of Physiology. 2009 ; Vol. 459, No. 1. pp. 93-103.
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