title: Butyrate produced by commensal bacteria potentiates phorbol esters induced AP-1 response in human intestinal epithelial cells.
abstract: The human intestine is a balanced ecosystem well suited for bacterial survival, colonization and growth, which has evolved to be beneficial both for the host and the commensal bacteria. Here, we investigated the effect of bacterial metabolites produced by commensal bacteria on AP-1 signaling pathway, which has a plethora of effects on host physiology. Using intestinal epithelial cell lines, HT-29 and Caco-2, stably transfected with AP-1-dependent luciferase reporter gene, we tested the effect of culture supernatant from 49 commensal strains. We observed that several bacteria were able to activate the AP-1 pathway and this was correlated to the amount of short chain fatty acids (SCFAs) produced. Besides being a major source of energy for epithelial cells, SCFAs have been shown to regulate several signaling pathways in these cells. We show that propionate and butyrate are potent activators of the AP-1 pathway, butyrate being the more efficient of the two. We also observed a strong synergistic activation of AP-1 pathway when using butyrate with PMA, a PKC activator. Moreover, butyrate enhanced the PMA-induced expression of c-fos and ERK1/2 phosphorylation, but not p38 and JNK. In conclusion, we showed that SCFAs especially butyrate regulate the AP-1 signaling pathway, a feature that may contribute to the physiological impact of the gut microbiota on the host. Our results provide support for the involvement of butyrate in modulating the action of PKC in colon cancer cells.
authors.affiliation: INRA, UMR 1319 MICALIS, Jouy-en-Josas, France.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Nepelska
authors.forename: Antonietta
authors.initials: A
authors.lastname: Cultrone
authors.forename: Fabienne
authors.initials: F
authors.lastname: Béguet-Crespel
authors.forename: Karine
authors.initials: K
authors.lastname: Le Roux
authors.forename: Joël
authors.initials: J
authors.lastname: Doré
authors.forename: Vermulugesan
authors.initials: V
authors.lastname: Arulampalam
authors.forename: Hervé M
authors.initials: HM
authors.lastname: Blottière
mesh_terms: D000943:Antigens, Differentiation / Q000378:metabolism; D002087:Butyrates / Q000378:metabolism* / Q000494:pharmacology; D018938:Caco-2 Cells; D002454:Cell Differentiation; D049109:Cell Proliferation; D017077:Culture Media, Conditioned; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology; D015870:Gene Expression; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D019073:HT29 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology* / Q000382:microbiology; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D020935:MAP Kinase Signaling System; D054892:Metagenome; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism* / Q000502:physiology; D015533:Transcriptional Activation
chemical_list: D000943:Antigens, Differentiation; D002087:Butyrates; C530104:CCND1 protein, human; D017077:Culture Media, Conditioned; D005227:Fatty Acids; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D019938:Cyclin D1; C012589:trichostatin A; D008156:Luciferases; D048049:Extracellular Signal-Regulated MAP Kinases; D013755:Tetradecanoylphorbol Acetate