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.

Immunology Letters
|May 2, 2012
PubMed

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.

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...