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

doi:10.1073/pnas.0711734105

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

*Department of Microbiology and Tumor and Cell Biology, Karolinska Institute, S-171 77 Stockholm, Sweden;
^†Department of Microbiology, National University of Singapore, Singapore 117597;
^‡Department of Biosciences and Nutrition, Novum, Karolinska Institute, S-141 86 Stockholm, Sweden; and
^§Genome Institute of Singapore, Singapore 138672

Communicated by Tak Wah Mak, University of Toronto, Toronto, ON, Canada, December 21, 2007 (received for review April 28, 2007)

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-γ1 (PPARγ1) 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-PPARγ1 becomes an immediate substrate for degradation possibly to curtail any extended transactivation. The involvement of PPARγ1 in a myriad of physiological processes further confirms that microflora-driven regulation might be important for a number of homeostatic strategies in the gut.

Footnotes

^¶To whom correspondence should be addressed. E-mail: sven.pettersson{at}ki.se
Author contributions: A.A. and L.A. contributed equally to this work; A.A., L.A., and V.A. performed research; L.A., S.W., G.G., and Y.K.L. contributed new reagents/analytic tools; A.A., L.A., S.P., and V.A. analyzed data; and A.A., L.A., J.-A.G., S.P., and V.A. wrote the paper.
Conflict of interest statement: J.-A.G. is a shareholder, research grant receiver, and consultant of KaroBio AB.