PMID- 21963787
OWN - NLM
STAT- MEDLINE
DCOM- 20120214
LR  - 20211203
IS  - 1528-0012 (Electronic)
IS  - 0016-5085 (Print)
IS  - 0016-5085 (Linking)
VI  - 142
IP  - 1
DP  - 2012 Jan
TI  - Campylobacter jejuni induces colitis through activation of mammalian target of 
      rapamycin signaling.
PG  - 86-95.e5
LID - 10.1053/j.gastro.2011.09.042 [doi]
AB  - BACKGROUND & AIMS: Campylobacter jejuni is the worldwide leading cause of 
      bacterial-induced enteritis. The molecular and cellular events that lead to 
      campylobacteriosis are poorly understood. We identify mammalian target of 
      rapamycin (mTOR) as a signaling pathway that leads to C jejuni-induced intestinal 
      inflammation. METHODS: Germ-free (control) or conventionally derived Il10(-/-) 
      mice that express enhanced green fluorescent protein (EGFP) under the control of 
      nuclear factor kappaB (Il10(-/-); NF-kappaB(EGFP) mice) were infected with C jejuni 
      (10(9) colony-forming units/mouse) for 12 days; their responses were determined 
      using histologic, semiquantitative reverse-transcription polymerase chain 
      reaction, fluorescence in situ hybridization, transmission electron microscopy, 
      and tissue culture analyses. mTOR signaling was blocked by daily intraperitoneal 
      injections of the pharmacologic inhibitor rapamycin (1.5 mg/kg). CD4(+) T cells 
      were depleted by intraperitoneal injections of antibodies against CD4 (0.5 
      mg/mouse every 3 days). Bacterial survival in splenocytes was measured using a 
      gentamycin killing assay. RESULTS: C jejuni induced intestinal inflammation, 
      which correlated with activation of mTOR signaling and neutrophil infiltration. 
      The inflamed intestines of these mice had increased levels of interleukin-1beta, 
      Cxcl2, interleukin-17a, and EGFP; C jejuni localized to colons and 
      extraintestinal tissues of infected Il10(-/-); NF-kappaB(EGFP) mice compared with 
      controls. Rapamycin, administered before or after introduction of C jejuni, 
      blocked C jejuni-induced intestinal inflammation and bacterial accumulation. 
      LC3II processing and killing of C jejuni were increased in splenocytes incubated 
      with rapamycin compared with controls. CONCLUSIONS: mTOR signaling mediates C 
      jejuni-induced colitis in Il10(-/-) mice, independently of T-cell activation. 
      Factors involved in mTOR signaling might be therapeutic targets for 
      campylobacteriosis.
CI  - Copyright (c) 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
FAU - Sun, Xiaolun
AU  - Sun X
AD  - Department of Medicine, University of North Carolina, Chapel Hill, North 
      Carolina, USA.
FAU - Threadgill, Deborah
AU  - Threadgill D
FAU - Jobin, Christian
AU  - Jobin C
LA  - eng
GR  - R01 DK073338/DK/NIDDK NIH HHS/United States
GR  - DK047700/DK/NIDDK NIH HHS/United States
GR  - R01 DK047700/DK/NIDDK NIH HHS/United States
GR  - DK073338/DK/NIDDK NIH HHS/United States
GR  - P30 DK034987/DK/NIDDK NIH HHS/United States
GR  - R21 AI082319-02/AI/NIAID NIH HHS/United States
GR  - R56 DK047700/DK/NIDDK NIH HHS/United States
GR  - R21 AI082319/AI/NIAID NIH HHS/United States
GR  - AI082319/AI/NIAID NIH HHS/United States
GR  - R01 DK047700-15/DK/NIDDK NIH HHS/United States
GR  - R01 DK073338-04/DK/NIDDK NIH HHS/United States
GR  - P30 DK34987/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Video-Audio Media
DEP - 20111001
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (Chemokine CXCL2)
RN  - 0 (Cxcl2 protein, mouse)
RN  - 0 (Il17a protein, mouse)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-17)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NF-kappa B)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (enhanced green fluorescent protein)
RN  - 130068-27-8 (Interleukin-10)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/immunology/microbiology
MH  - Campylobacter 
      Infections/complications/genetics/immunology/*microbiology/pathology/prevention & 
      control
MH  - Campylobacter jejuni/*pathogenicity
MH  - Cells, Cultured
MH  - Chemokine CXCL2/metabolism
MH  - Colitis/enzymology/genetics/immunology/*microbiology/pathology/prevention & 
      control
MH  - Colon/drug effects/enzymology/immunology/*microbiology/pathology
MH  - Disease Models, Animal
MH  - Enzyme Activation
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - In Situ Hybridization, Fluorescence
MH  - Inflammation Mediators/metabolism
MH  - Injections, Intraperitoneal
MH  - Interleukin-10/deficiency/genetics
MH  - Interleukin-17/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Mice
MH  - Mice, 129 Strain
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Microscopy, Electron, Transmission
MH  - NF-kappa B/genetics
MH  - Neutrophil Infiltration
MH  - Neutrophils/immunology/microbiology
MH  - Protein Kinase Inhibitors/administration & dosage
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Signal Transduction/drug effects
MH  - Sirolimus/administration & dosage
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
MH  - Time Factors
PMC - PMC3253301
MID - NIHMS328868
EDAT- 2011/10/04 06:00
MHDA- 2012/02/15 06:00
PMCR- 2013/01/01
CRDT- 2011/10/04 06:00
PHST- 2011/03/23 00:00 [received]
PHST- 2011/08/30 00:00 [revised]
PHST- 2011/09/20 00:00 [accepted]
PHST- 2011/10/04 06:00 [entrez]
PHST- 2011/10/04 06:00 [pubmed]
PHST- 2012/02/15 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - S0016-5085(11)01367-9 [pii]
AID - 10.1053/j.gastro.2011.09.042 [doi]
PST - ppublish
SO  - Gastroenterology. 2012 Jan;142(1):86-95.e5. doi: 10.1053/j.gastro.2011.09.042. 
      Epub 2011 Oct 1.