MicroR-146 blocks the activation of M1 macrophage by targeting signal transducer and activator of transcription 1 in hepatic schistosomiasis.

Abstract

Schistosomiasis is a chronic disease caused by the parasite of the Schistosoma genus and is characterized by egg-induced hepatic granulomas and fibrosis. Macrophages play a central role in schistosomiasis with several studies highlighting their differentiation into M2 cells involved in the survival of infected mice through limitation of immunopathology. However, little is known regarding the mechanisms of regulating macrophage differentiation. Here, we showed that the early stage of infection by Schistosoma japonicum induced expression of type 1T-helper-cell (Th1) cytokine, interferon-γ (IFN-γ), leading to increase in M1 cells. However, the presence of liver-trapped eggs induced the expression of Th2 cytokines including interleukin-4 (IL-4), IL-10, and IL-13 that upregulated the transcription of miR-146b by activating signal transducer and activator of transcription 3/6 (STAT3/6) that bind to the promoter of the pre-miR-146b gene. We found that the miR-146a/b was significantly upregulated in macrophages during the progression of hepatic schistosomiasis. The elevated miR-146a/b inhibited the IFN-γ-induced differentiation of macrophages to M1 cells through targeting STAT1. Our data indicate the protective roles of miR-146a/b in hepatic schistosomiasis through regulating the differentiation of macrophages into M2 cells.

• Authors: Xing He, Rui Tang, Yue Sun, Yan-Ge Wang, Kui-Yang Zhen, Dong-Mei Zhang, Wei-Qing Pan
• Journal: EBioMedicine (EBioMedicine) Vol. 13 Pg. 339-347 (Nov 2016) ISSN: 2352-3964 [Electronic] Netherlands
• PMID: 27780686 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Cytokines
• MicroRNAs
• Mirn146 microRNA, mouse
• STAT1 Transcription Factor

Topics

• Animals
• Cytokines (metabolism)
• Disease Models, Animal
• Disease Progression
• Gene Expression
• Liver Diseases, Parasitic (genetics, parasitology, pathology)
• Macrophage Activation (genetics, immunology)
• Macrophages (cytology, immunology, metabolism)
• Male
• Mice
• MicroRNAs (genetics)
• Models, Biological
• RNA Interference
• STAT1 Transcription Factor (genetics)
• Schistosomiasis (genetics, parasitology, pathology)
• Th2 Cells (immunology, metabolism)