Hsp70 protects macrophages infected with Salmonella choleraesuis against TNF-α-induced cell death

Hitoshi Nishimura, Masashi Emoto, Keiko Kimura, Yasunobu Yoshikai

    Research output: Contribution to journalArticle

    33 Citations (Scopus)

    Abstract

    Hsp70 plays an important role in cytoprotection against tumor necrosis factor (TNF) α-mediated cytotoxicity. To investigate the role of Hsp70 in cytoprotection during Salmonella infection, we examined endogenous Hsp70 induction and TNF-α production in a monocyte/macrophage line, J774A.1, after infection with a virulent strain of Salm. choleraesuis RF-1 carrying a 50 kb virulent plasmid or the plasmid-cured avirulent strain 31N-1. Intracellular bacteria progressively increased in J774A.1 cells phagocytosing virulent RF-1 bacteria, whereas such progressive growth was not evident in J774A.1 cells phagocytosing avirulent 31N-1 bacteria. On the contrary, J774A.1 cells infected with virulent RF-1 bacteria expressed less Hsp70 than those infected with avirulent 31N-1 bacteria. The level of TNF-α production by J774A.1 infected with virulent RF-1 was much the same as that by J774A.1 infected with avirulent 31N-1. J774A.1 infected with virulent RF-1 died spontaneously; death was inhibited by the addition of anti-TNF-α mAb. Although the frequency of dead J774A.1 with hypodiploid DNA content increased only marginally after infection with avirulent 31N-1, treatment with Hsp70 anti-sense oligonucleotide resulted in a dramatic increase of dead cells in the infected macrophages. Taken together, these results suggest that Hsp70 induced in infected macrophages plays an important role in host defense against Salmonella infection by protecting the macrophages against TNF α-induced cell death. Furthermore, cell death due to impaired endogenous Hsp synthesis in the phagocytes implies a novel pathogenic mechanism for virulence of Salm. choleraesuis RF-1.

    Original languageEnglish
    Pages (from-to)50-59
    Number of pages10
    JournalCell Stress and Chaperones
    Volume2
    Issue number1
    DOIs
    Publication statusPublished - Mar 1 1997

    Fingerprint

    Salmonella
    Macrophages
    Cell death
    Bacteria
    Cell Death
    Tumor Necrosis Factor-alpha
    Cytophagocytosis
    Cytoprotection
    Salmonella Infections
    Plasmids
    Antisense Oligonucleotides
    Cytotoxicity
    Phagocytes
    Infection
    Virulence
    Monocytes
    DNA
    Growth

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Cell Biology

    Cite this

    Hsp70 protects macrophages infected with Salmonella choleraesuis against TNF-α-induced cell death. / Nishimura, Hitoshi; Emoto, Masashi; Kimura, Keiko; Yoshikai, Yasunobu.

    In: Cell Stress and Chaperones, Vol. 2, No. 1, 01.03.1997, p. 50-59.

    Research output: Contribution to journalArticle

    Nishimura, Hitoshi ; Emoto, Masashi ; Kimura, Keiko ; Yoshikai, Yasunobu. / Hsp70 protects macrophages infected with Salmonella choleraesuis against TNF-α-induced cell death. In: Cell Stress and Chaperones. 1997 ; Vol. 2, No. 1. pp. 50-59.
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    abstract = "Hsp70 plays an important role in cytoprotection against tumor necrosis factor (TNF) α-mediated cytotoxicity. To investigate the role of Hsp70 in cytoprotection during Salmonella infection, we examined endogenous Hsp70 induction and TNF-α production in a monocyte/macrophage line, J774A.1, after infection with a virulent strain of Salm. choleraesuis RF-1 carrying a 50 kb virulent plasmid or the plasmid-cured avirulent strain 31N-1. Intracellular bacteria progressively increased in J774A.1 cells phagocytosing virulent RF-1 bacteria, whereas such progressive growth was not evident in J774A.1 cells phagocytosing avirulent 31N-1 bacteria. On the contrary, J774A.1 cells infected with virulent RF-1 bacteria expressed less Hsp70 than those infected with avirulent 31N-1 bacteria. The level of TNF-α production by J774A.1 infected with virulent RF-1 was much the same as that by J774A.1 infected with avirulent 31N-1. J774A.1 infected with virulent RF-1 died spontaneously; death was inhibited by the addition of anti-TNF-α mAb. Although the frequency of dead J774A.1 with hypodiploid DNA content increased only marginally after infection with avirulent 31N-1, treatment with Hsp70 anti-sense oligonucleotide resulted in a dramatic increase of dead cells in the infected macrophages. Taken together, these results suggest that Hsp70 induced in infected macrophages plays an important role in host defense against Salmonella infection by protecting the macrophages against TNF α-induced cell death. Furthermore, cell death due to impaired endogenous Hsp synthesis in the phagocytes implies a novel pathogenic mechanism for virulence of Salm. choleraesuis RF-1.",
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