Molecular mechanisms involved in the IL-6-mediated upregulation of indoleamine 2,3-dioxygenase 1 (IDO1) expression in the chorionic villi and decidua of women in early pregnancy.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 100967799 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2393 (Electronic) Linking ISSN: 14712393 NLM ISO Abbreviation: BMC Pregnancy Childbirth Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central, [2001-
    • Subject Terms:
      Chorionic Villi* ; Interleukin-6*; Pregnancy ; Humans ; Female ; Suppressor of Cytokine Signaling 3 Protein/metabolism ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Up-Regulation ; Suppressor of Cytokine Signaling Proteins/genetics ; Suppressor of Cytokine Signaling Proteins/metabolism ; Decidua
    • Abstract:
      Background: IL-6 induces the upregulation of indoleamine 2,3-dioxygenase (IDO1) at the maternal-foetal interface, but the regulation mechanisms of IDO1 by IL-6 at this interface have not been fully understood.
      Methods: Western blotting, qRT-PCR and/or immunohistochemistry were employed to measure the expression of IDO1, IL-6, SHP-1/2, SOCS3 and STAT3/p (STAT3 and pSTAT3) in tissues of chorionic villi and decidua (TCVD) in vivo and in cultured TCVD that were treated with IL-6 in the presence or absence of an IL-6 inhibitor.
      Results: Mutually positive relationships among the protein levels of IL-6, IDO1, SHP-1/2 and STAT3/p was observed, and the expression of IDO1, SHP-1/2 and STAT3/p was increased in a dose-dependent manner in TCVD in vivo and in cultured TCVD treated with IL-6 at increasing concentrations (0-100 ng/ml). The level of IL-6 was negatively related to SOCS3 level in TCVD. The expression of SOCS3 was increased in a dose-dependent manner, and SOCS3 level was positively correlated with SHP-1, SHP-2 and STAT3/p level in cultured TCVD treated with 0-2 ng/ml IL-6; however, opposite results were observed after treatment with 2-100 ng/ml IL-6. The IL-6-induced upregulation of IDO1, SHP-1, SHP-2 and STAT3/p expression could be reversed, while the IL-6-induced upregulation of SOCS3 expression was exacerbated by Corylifol A.
      Conclusions: In normal pregnancy, IL-6 upregulates the expression of IDO1 by promoting SHP-1/2 expression via STAT3/p and simultaneously negatively regulates the expression of SOCS3. High expression of IL-6 causes the upregulation of IDO1 expression and the downregulation of SOCS-3 expression, which may be beneficial for maintaining immunological tolerance.
      (© 2022. The Author(s).)
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    • Contributed Indexing:
      Keywords: IDO1; IL-6; SOCS3; maternal-foetal tolerance
    • Accession Number:
      0 (Interleukin-6)
      0 (Suppressor of Cytokine Signaling 3 Protein)
      0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
      0 (Suppressor of Cytokine Signaling Proteins)
    • Publication Date:
      Date Created: 20221231 Date Completed: 20230103 Latest Revision: 20230103
    • Publication Date:
      20231215
    • Accession Number:
      PMC9805015
    • Accession Number:
      10.1186/s12884-022-05307-5
    • Accession Number:
      36587196