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 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.
Are
Alexandra
A
Department of Microbiology and Tumor and Cell Biology, Karolinska Institute, S-171 77 Stockholm, Sweden.
Aronsson
Linda
L
Wang
Shugui
S
Greicius
Gediminas
G
Lee
Yuan Kun
YK
Gustafsson
Jan-Ake
JA
Pettersson
Sven
S
Arulampalam
Velmurugesan
V
D003106:Colon / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D004247:DNA / Q000378:metabolism; D013293:Enterococcus faecalis / Q000502:physiology*; D015870:Gene Expression; D019073:HT29 Cells; D006801:Humans; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D000070780:Perilipin-2; D010766:Phosphorylation; D011485:Protein Binding
D008024:Ligands; D008565:Membrane Proteins; D047495:PPAR gamma; D000070780:Perilipin-2; D016753:Interleukin-10; D004247:DNA