miR-155 influences cell-mediated immunity in Balb/c mice treated with aflatoxin M1

Drug Chem Toxicol. 2021 Jan;44(1):39-46. doi: 10.1080/01480545.2018.1556682. Epub 2019 Feb 11.

Abstract

Aflatoxin M1 (AFM1) is a 4-hydroxylated metabolite of aflatoxin B1 (AFB1). It induces various toxicological effects including immunotoxicity. In the present study, we investigated the effects of AFM1 on immune system and its modulation by MicroRNA (miR)-155. AFM1 was administered intraperitoneally at doses of 25 and 50 µg/kg for 28 days to Balb/c mice and different immune system parameters were analyzed. The levels of miR-155 and targeted proteins were evaluated in isolated T cells from spleens of mice. Spleen weight was reduced in mice exposed to AFM1 compared to negative control. Proliferation of splenocytes in response to phytohemagglutinin-A was reduced in mice exposed to AFM1. IFN-γ was decreased in mice exposed to AFM1, whereas IL-10 was increased. Concentration of IL-4 did not change different in mice exposed to AFM1 compared to negative control. Exposure to AFM1 reduced the expression of miR-155. Significant upregulation of phosphatidylinositol-3, 4, 5-trisphosphate 5-phosphatase 1 (Ship1) and suppressor of cytokine signaling 1 (Socs1) was observed in isolated T cells from spleens of mice treated with AFM1, but the transcription factor Maf (c-MAF) was not affected. These results suggest that miR-155 and targeted proteins might be involved in the immunotoxicity observed in mice exposed to AFM1.

Keywords: Immunotoxicity; Ship1; Socs1; aflatoxin M1; micro-RNA.

MeSH terms

  • Aflatoxin M1 / administration & dosage
  • Aflatoxin M1 / toxicity*
  • Animals
  • Cell Proliferation / drug effects
  • Cytokines / metabolism
  • Gene Expression Regulation
  • Immunity, Cellular / drug effects*
  • Injections, Intraperitoneal
  • Lymphocyte Activation / drug effects
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / metabolism
  • Signal Transduction
  • Spleen / drug effects*
  • Spleen / immunology
  • Spleen / metabolism
  • Suppressor of Cytokine Signaling 1 Protein / metabolism
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Cytokines
  • MicroRNAs
  • Mirn155 microRNA, mouse
  • Socs1 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • Aflatoxin M1
  • Inpp5d protein, mouse
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases