title: Autophagy in the intestinal epithelium reduces endotoxin-induced inflammatory responses by inhibiting NF-κB activation.
abstract: Autophagy is a lysosomal degradation pathway that is essential for survival, differentiation, development and homeostasis. There is growing evidence that impaired autophagy leads to the pathogenesis of diverse diseases. However, the role of autophagy in intestinal epithelium is not clearly understood, although previous studies have pointed out the possibility for the relationships of autophagy with bowel inflammation. In this study, we investigated the involvement of autophagy in intestinal epithelium with inflammatory responses. We generated the mice with a conditional deletion of Atg7, which is one of the autophagy regulated gene, in intestinal epithelium. In Atg7-deficient small intestinal epithelium, LPS-induced production of TNF-α and IL-1β mRNA was enhanced in comparison to the control small intestinal tissues. In addition, the degree of LPS-induced activation of NF-κB was promoted in Atg7-deficient intestinal epithelium. These results demonstrate that autophagy can attenuate endotoxin-induced inflammatory responses in intestinal epithelium resulting in the maintenance of intestinal homeostasis.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Fujishima
authors.forename: Shin
authors.initials: S
authors.lastname: Nishiumi
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Masuda
authors.forename: Jun
authors.initials: J
authors.lastname: Inoue
authors.forename: Ngoc Mai Thin
authors.initials: NM
authors.lastname: Nguyen
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Irino
authors.forename: Masaaki
authors.initials: M
authors.lastname: Komatsu
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kutsumi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.forename: Masaru
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000071193:Autophagy-Related Protein 7; D001483:Base Sequence; D004247:DNA / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D053583:Interleukin-1beta / Q000235:genetics; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C502661:Atg7 protein, mouse; D017931:DNA Primers; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D000071193:Autophagy-Related Protein 7