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 journalArticlepeer-review

    25 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

    Keywords

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

    ASJC Scopus subject areas

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

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