Soluble factors from Lactobacillus GG activate MAPKs and induce cytoprotective heat shock proteins in intestinal epithelial cells.
Conditioned media from the probiotic Lactobacillus GG (LGG-CM) induce heat shock protein (Hsp) expression in intestinal epithelial cells. LGG-CM induces both Hsp25 and Hsp72 in a time- and concentration-dependent manner. These effects are mediated by a low-molecular-weight peptide that is acid and heat stable. DNA microarray experiments demonstrate that Hsp72 is one of the most highly upregulated genes in response to LGG-CM treatment. Real-time PCR and electrophoretic mobility shift assay confirm that regulation of Hsp induction is at least in part transcriptional in nature, involving heat shock factor-1. Although Hsps are not induced for hours after exposure, transient exposure to LGG-CM is sufficient to initiate the signal for Hsp induction, suggesting that signal transduction pathways may be involved. Experiments confirm that LGG-CM modulates the activity of certain signaling pathways in intestinal epithelial cells by activating MAP kinases. Inhibitors of p38 and JNK block the expression of Hsp72 normally induced by LGG-CM. Functional studies indicate that LGG-CM treatment of gut epithelial cells protects them from oxidant stress, perhaps by preserving cytoskeletal integrity. By inducing the expression of cytoprotective Hsps in gut epithelial cells, and by activating signal transduction pathways, the peptide product(s) secreted by LGG may contribute to the beneficial clinical effects attributed to this probiotic.
Tao
Yun
Y
Martin Boyer and IBD Research Center, University of Chicago, 5841 S. Maryland Ave., MC6084, IL 60637, USA.
Drabik
Kenneth A
KA
Waypa
Tonya S
TS
Musch
Mark W
MW
Alverdy
John C
JC
Schneewind
Olaf
O
Chang
Eugene B
EB
Petrof
Elaine O
EO
D000818:Animals; D002460:Cell Line; D002700:Chloramines / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000737:chemistry; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism; D007778:Lactobacillus / Q000737:chemistry* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016877:Oxidants / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D019936:Probiotics / Q000737:chemistry / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism
D002700:Chloramines; D017077:Culture Media, Conditioned; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D016877:Oxidants; D010455:Peptides; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; C030816:chloramine