PMID:18234854

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Citation

Are, A, Aronsson, L, Wang, S, Greicius, G, Lee, YK, Gustafsson, JA, Pettersson, S and Arulampalam, V (2008) Enterococcus faecalis from newborn babies regulate endogenous PPARgamma activity and IL-10 levels in colonic epithelial cells. Proc. Natl. Acad. Sci. U.S.A. 105:1943-8

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.

Links

PubMed PMC2538862 Online version:10.1073/pnas.0711734105

Keywords

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; PPAR gamma/metabolism; Phosphorylation; Protein Binding

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