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Lipopolysaccharide shock reveals immune function of indoleamine 2,3-dioxygenase 2 through regulation of IL-6/stat3 signalling, 2018, Yamamoto et al

Discussion in 'Other health news and research' started by FMMM1, Jul 12, 2021.

  1. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    Last edited by a moderator: Nov 3, 2021
  2. Simon M

    Simon M Senior Member (Voting Rights)

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    Abstract

    Indoleamine 2,3-dioxygenase 2 (Ido2) is a recently identified catalytic enzyme in the tryptophan-kynurenine pathway that is expressed primarily in monocytes and dendritic cells.

    To elucidate the biological role of Ido2 in immune function, we introduced lipopolysaccharide (LPS) endotoxin shock to Ido2 knockout (Ido2 KO) mice, which led to higher mortality than that in the wild type (WT) mice. LPS-treated Ido2 KO mice had increased production of inflammatory cytokines (including interleukin-6; IL-6) in serum and signal transducer and activator of transcription 3 (stat3) phosphorylation in the spleen.

    Moreover, the peritoneal macrophages of LPS-treated Ido2 KO mice produced more cytokines than did the WT mice. By contrast, the overexpression of Ido2 in the murine macrophage cell line (RAW) suppressed cytokine production and decreased stat3 expression. Finally, RAW cells overexpressing Ido2 did not alter nuclear factor κB (NF-κB) or stat1 expression, but IL-6 and stat3 expression decreased relative to the control cell line.

    These results reveal that Ido2 modulates IL-6/stat3 signalling and is induced by LPS, providing novel options for the treatment of immune disorders.

    Some info that might help


    1. In terms of the IDO2 metabolic trap hypothesis, we already knew that the key cells of interest were dendritic cells (important in presenting antigens to the immune system to fire it up). I wasn't aware of the monocyte connection.

    2. Lipopolysaccharide (LPS) is found in the outer walls of gram-negative bacteria, and is a classic way to poke the immune system into action in animal models.

    3. IL-6/stat3 signalling lets cells know there is a threat and leads to upregulation of a specific set of genes that lead to longer-term changes to boost the immune system (I forget the details).
     
    Hutan, DokaGirl, Lidia and 12 others like this.

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