Enterococcus faecalis from newborn babies regulate endogenous PPARgamma activity and IL-10 levels in colonic epithelial cells

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 s...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 105; no. 6; p. 1943
Main Authors Are, Alexandra, Aronsson, Linda, Wang, Shugui, Greicius, Gediminas, Lee, Yuan Kun, Gustafsson, Jan-Ake, Pettersson, Sven, Arulampalam, Velmurugesan
Format Journal Article
LanguageEnglish
Published United States 12.02.2008
Subjects
Colon - cytology
Colon - metabolism
Colon - microbiology
DNA - metabolism
Enterococcus faecalis - physiology
Gene Expression
HT29 Cells
Humans
Infant, Newborn
Interleukin-10 - genetics
Interleukin-10 - metabolism
Intestinal Mucosa - cytology
Intestinal Mucosa - metabolism
Intestinal Mucosa - microbiology
Ligands
Membrane Proteins - genetics
Membrane Proteins - metabolism
Perilipin-2
Phosphorylation
PPAR gamma - metabolism
Protein Binding
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Summary: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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ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.0711734105