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Soluble bioactive microbial mediators regulate proteasomal degradation and autophagy to protect against inflammation-induced stress.
Inaba, Yuhei; Ueno, Nobuhiro; Numata, Masatsugu; Zhu, Xiaorong; Messer, Jeannette S; Boone, David L; Fujiya, Mikihiro; Kohgo, Yutaka; Musch, Mark W; Chang, Eugene B.
Afiliación
  • Inaba Y; Department of Medicine, Inflammatory Bowel Disease Research Center, The University of Chicago, Chicago, Illinois; Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
  • Ueno N; Department of Medicine, Inflammatory Bowel Disease Research Center, The University of Chicago, Chicago, Illinois; Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
  • Numata M; Department of Medicine, Inflammatory Bowel Disease Research Center, The University of Chicago, Chicago, Illinois; Division of Life Style and Digestive Diseases, Kagoshima Medical University, Kagoshima, Japan.
  • Zhu X; Department of Medicine, Inflammatory Bowel Disease Research Center, The University of Chicago, Chicago, Illinois.
  • Messer JS; Department of Medicine, Inflammatory Bowel Disease Research Center, The University of Chicago, Chicago, Illinois.
  • Boone DL; Department of Microbiology and Immunology, Indiana University School of Medicine-South Bend, South Bend, Indiana.
  • Fujiya M; Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
  • Kohgo Y; Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
  • Musch MW; Department of Medicine, Inflammatory Bowel Disease Research Center, The University of Chicago, Chicago, Illinois.
  • Chang EB; Department of Medicine, Inflammatory Bowel Disease Research Center, The University of Chicago, Chicago, Illinois; echang@medicine.bsd.uchicago.edu.
Am J Physiol Gastrointest Liver Physiol ; 311(4): G634-G647, 2016 10 01.
Article en En | MEDLINE | ID: mdl-27514476
Bifidobacterium breve and other Gram-positive gut commensal microbes protect the gastrointestinal epithelium against inflammation-induced stress. However, the mechanisms whereby these bacteria accomplish this protection are poorly understood. In this study, we examined soluble factors derived from Bifidobacterium breve and their impact on the two major protein degradation systems within intestinal epithelial cells, proteasomes and autophagy. Conditioned media from gastrointestinal Gram-positive, but not Gram-negative, bacteria activated autophagy and increased expression of the autophagy proteins Atg5 and Atg7 along with the stress response protein heat shock protein 27. Specific examination of media conditioned by the Gram-positive bacterium Bifidobacterium breve (Bb-CM) showed that this microbe produces small molecules (<3 kDa) that increase expression of the autophagy proteins Atg5 and Atg7, activate autophagy, and inhibit proteasomal enzyme activity. Upregulation of autophagy by Bb-CM was mediated through MAP kinase signaling. In vitro studies using C2BBe1 cells silenced for Atg7 and in vivo studies using mice conditionally deficient in intestinal epithelial cell Atg7 showed that Bb-CM-induced cytoprotection is dependent on autophagy. Therefore, this work demonstrates that Gram-positive bacteria modify protein degradation programs within intestinal epithelial cells to promote their survival during stress. It also reveals the therapeutic potential of soluble molecules produced by these microbes for prevention and treatment of gastrointestinal disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Estrés Fisiológico / Complejo de la Endopetidasa Proteasomal / Mucosa Intestinal Límite: Animals Idioma: En Revista: Am J Physiol Gastrointest Liver Physiol Asunto de la revista: FISIOLOGIA / GASTROENTEROLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Estrés Fisiológico / Complejo de la Endopetidasa Proteasomal / Mucosa Intestinal Límite: Animals Idioma: En Revista: Am J Physiol Gastrointest Liver Physiol Asunto de la revista: FISIOLOGIA / GASTROENTEROLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos