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Published on: June 24, 2020
Enterococcus faecalis from newborn babies regulate endogenous PPARgamma activity and IL-10 levels in colonic
Alexandra Are1, Linda Aronsson, Shugui Wang
1Department of Microbiology and Tumor and Cell Biology, Karolinska Institute, S-171 77 Stockholm, Sweden.
Insights
Commensal bacteria like Enterococcus faecalis regulate gut development by activating nuclear receptors. This bacterial interaction enhances DNA binding and gene activation, crucial for immune function and gut homeostasis.
Area of Science:
- Microbiology
- Gastroenterology
- Molecular Biology
Background:
- Postembryonic development of the gastrointestinal tract is influenced by gut microbiota.
- Commensal bacteria interact with host cells to regulate maturation processes.
Purpose of the Study:
- To investigate the role of Enterococcus faecalis in regulating nuclear receptor activity in the colon.
- To elucidate the molecular mechanisms by which bacteria influence host gene expression.
Main Methods:
- Utilized colonic cell lines and primary colonic cells.
- Analyzed the phosphorylation and DNA binding activity of peroxisome proliferator-activated receptor-gamma1 (PPARgamma1).
- Assessed the transcriptional activation of downstream target genes, including IL-10.
Main Results:
- Enterococcus faecalis regulates PPARgamma1 activity via phosphorylation in colonic cells.
- This leads to increased DNA binding and transcriptional activation of genes like IL-10.
- Phospho-PPARgamma1 is rapidly degraded, suggesting tight regulation of transactivation.
Conclusions:
- Microflora-driven regulation of PPARgamma1 is important for gut homeostasis.
- Bacterial interactions with nuclear receptors play a key role in gastrointestinal development and immune modulation.
Abstract:
The postembryonic development of the gastrointestinal tract is subject to regulation by the colonizing microbiota. This maturation process requires the commensal bacteria to cross-talk with host cells by way of recognizing receptors and inducing signaling pathways to activate transcription factors such as the nuclear receptors. Here, we show that in colonic cell lines and in primary colonic cells, Enterococcus faecalis isolated from newborn babies possess the ability to regulate peroxisome proliferator-activated receptor-gamma1 (PPARgamma1) activity through phosphorylation. This results in elevated DNA binding and transcriptional activation of downstream target genes, including IL-10, a cytokine known to modulate innate immune function. Furthermore, phosphorylation appears tightly regulated as phospho-PPARgamma1 becomes an immediate substrate for degradation possibly to curtail any extended transactivation. The involvement of PPARgamma1 in a myriad of physiological processes further confirms that microflora-driven regulation might be important for a number of homeostatic strategies in the gut.
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