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Published on: August 13, 2013
miR-155 mediates suppressive effect of progesterone on TLR3, TLR4-triggered immune response
Yixi Sun1, Jiaojiao Cai, Feng Ma
1Institute of Reproduction and Genetics, School of Medicine, Zhejiang University, 866 Yuhang Tang Road, Hangzhou 310058, China.
Abstract:
It has been demonstrated that progesterone has immune suppressive properties and can inhibit Toll-like receptor 4 (TLR4)-triggered immune response. Multiple microRNAs are induced in innate immune cells, among them miR-155, miR-146a and miR-21 are particularly ubiquitous. In this study, we investigated the potential roles of miR-155 in progesterone-mediated regulation of innate immune responses. We found that progesterone pre-treatment suppressed LPS- and poly(I:C)-induced miR-155 expression in macrophages. Increasing the activity of miR-155, significantly attenuated the progesterone's inhibition on LPS-induced IL-6 as well as LPS- and poly(I:C)-induced IFN-β expression in macrophages. Furthermore, we demonstrated that progesterone up-regulated LPS-induced SOCS1 expression while overexpression of miR-155 inhibited SOCS1 expression. In conclusion, the present study has demonstrated that progesterone suppresses TLRs-triggered immune response by regulating miR-155, and the decreased miR-155 contributes to inhibit TLR-induced IL-6 and IFN-β via increased SOCS1 expression.
Insights
Progesterone suppresses innate immune responses by regulating microRNA-155 (miR-155). Decreased miR-155 levels enhance Toll-like receptor-induced IL-6 and IFN-β expression through increased SOCS1, revealing a novel immune regulatory pathway.
Area of Science:
- Immunology
- Molecular Biology
- Endocrinology
Background:
- Progesterone exhibits immune-suppressive properties, notably inhibiting Toll-like receptor 4 (TLR4)-mediated responses.
- MicroRNAs, including miR-155, miR-146a, and miR-21, are crucial regulators of innate immunity.
Purpose of the Study:
- To investigate the role of miR-155 in progesterone's regulation of innate immune responses.
- To elucidate the molecular mechanisms underlying progesterone's immunomodulatory effects.
Main Methods:
- Macrophages were treated with progesterone, lipopolysaccharide (LPS), and poly(I:C).
- Expression levels of miR-155, IL-6, IFN-β, and SOCS1 were quantified.
- miR-155 activity was modulated to assess its impact on immune responses.
Main Results:
- Progesterone suppressed LPS- and poly(I:C)-induced miR-155 expression in macrophages.
- Enhanced miR-155 activity counteracted progesterone's inhibition of LPS-induced IL-6 and IFN-β.
- Progesterone upregulated LPS-induced SOCS1, while miR-155 overexpression inhibited SOCS1.
Conclusions:
- Progesterone suppresses TLR-triggered immune responses via regulation of miR-155.
- Reduced miR-155 contributes to the inhibition of TLR-induced IL-6 and IFN-β by increasing SOCS1 expression.
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