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

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 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.

Graphical Abstract

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).

Highlights

• 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.

Keywords:

• Immunotoxicity
• Ship1
• Socs1
• micro-RNA
• aflatoxin M1

Disclosure statement

Professor JPG was supported by the Canada Research Chair program, the 2012 ‘High Level Foreign Experts’ (#GDT20143200016) program funded by the State Administration of Foreign Experts Affairs, the P.R. China to Nanjing University and the Einstein Professor Program of the Chinese Academy of Sciences and a Distinguished Visiting Professorship in the School of Biological Sciences of the University of Hong Kong. The other authors declare no conflicts of interest.

Additional information

Funding

The authors are thankful to the Vice Chancellor of Research, Mashhad University of Medical Sciences and Iran National Science Foundation (INSF) for financial support.