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

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 AFM_1, 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. The Immunotoxic effects of AFM₁ on T cell functions. Exposure to AFM₁ reduced the expression of miR-155. Significant upregulation of Ship1 and Socs1 was observed in isolated T cells from spleens of mice treated with AFM_1, but the c-MAF was not affected. Since Ship1 is a functional target of miR-155 that modulates production of IFN-γ, miR-155 may play a role in AFM₁-induced Th₁ response suppression (DTH) through targeting of this protein (↑ increase; ↓ decrease). AFM₁ inhibited cell-mediated immunity. Exposure of mice to AFM₁ resulted in a significant decrease in expression of miR-155. Exposure of mice to AFM₁ resulted in up-regulation of Ship1 and Socs1. [ABSTRACT FROM AUTHOR]