Mechanisms underlying the suppression of inflammatory responses in peritoneal macrophages of middle-aged mice

Ken Shirato*, Kazuhiko Imaizumi

*この研究の対応する著者

    研究成果: Chapter

    2 被引用数 (Scopus)

    抄録

    We investigated the molecular mechanisms underlying the deterioration of macrophage inflammatory responses in middle-aged mice, focusing on the agerelated reduction in protein synthesis rate. Peritoneal macrophages were isolated from male BALB/c mice aged 2 months (young) and 12 months (middle-aged), and stimulated with lipopolysaccharide (LPS). At the protein level, LPS-stimulated proinflammatory cytokine release and intracellular accumulation of bactericidal mediators from macrophages were clearly lower in middle-aged mice than in young mice. However, LPS caused a marked increase in the mRNA expression of these genes in the macrophages of both young and middle-aged mice. Moreover, LPS induced comparable phosphorylation levels of signaling proteins downstream of toll-like receptor (TLR) in young and middle-aged mice. In contrast, levels of the inactive (phosphorylated) form of eukaryotic initiation factor 2α (eIF-2α) were higher in macrophages from middle-aged mice than in macrophages from young mice. Suppression of the LPS-stimulated inflammatory responses observed in middleaged mice could be mimicked by treating the murine macrophage RAW264.7 cells with salubrinal, an inhibitor of the phosphatase that dephosphorylates eIF-2α. In conclusion, post-transcriptional suppression of macrophage inflammatory responses during middle age requires phosphorylation of eIF-2α.

    本文言語English
    ホスト出版物のタイトルPhysical Activity, Exercise, Sedentary Behavior and Health
    出版社Springer Japan
    ページ193-202
    ページ数10
    ISBN(印刷版)9784431553335, 9784431553328
    DOI
    出版ステータスPublished - 2015 1 1

    ASJC Scopus subject areas

    • 医学(全般)
    • 工学(全般)

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