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Chitinase 3-like 1 synergistically activates IL6-mediated STAT3 phosphorylation in intestinal epithelial cells in murine models of infectious colitis.

AbstractBACKGROUND:
Chitinase 3-like 1 (CHI3L1) is an inducible molecule on intestinal epithelial cells during the development of inflammatory bowel disease.
METHODS:
To investigate the role of CHI3L1 in bacterial infectious colitis, we orally inoculated pathogenic Salmonella typhimurium and potentially pathogenic adherent-invasive Escherichia coli (AIEC) LF82 virulent strain into C57Bl/6 wild-type mice or CHI3L1 knockout (KO) mice.
RESULTS:
Both S. typhimurium and AIEC LF82 were found to efficiently induce severe intestinal inflammation in wild-type mice but not in CHI3L1 KO mice. These bacteria-infected CHI3L1 KO mice exhibit decreased cellular infiltration, bacterial translocation, and production of interleukin (IL)-6 and IL-22, as compared with those of wild-type mice. More importantly, CHI3L1 KO mice displayed aberrant STAT3 activation after bacterial infections. Co-stimulation of CHI3L1 and IL-6, but not IL-22, synergistically activates STAT3 signaling pathway in intestinal epithelial cells in an NF-κB/MAPK-dependent manner.
CONCLUSIONS:
CHI3L1 promotes the onset of selected gram-negative bacterial infectious colitis through IL-6/STAT3 pathway.
AuthorsHoa T Tran, In-Ah Lee, Daren Low, Alan Kamba, Atsushi Mizoguchi, Hai N Shi, Chun G Lee, Jack A Elias, Emiko Mizoguchi
JournalInflammatory bowel diseases (Inflamm Bowel Dis) Vol. 20 Issue 5 Pg. 835-46 (May 2014) ISSN: 1536-4844 [Electronic] United States
PMID24694795 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Glycoproteins
  • Interleukin-6
  • NF-kappa B
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • chitinase 3-like 1, mouse
Topics
  • Animals
  • Bacterial Adhesion
  • Blotting, Western
  • Cells, Cultured
  • Colitis (metabolism, microbiology, pathology)
  • Disease Models, Animal
  • Epithelial Cells (metabolism, microbiology, pathology)
  • Escherichia coli (pathogenicity)
  • Escherichia coli Infections (metabolism, microbiology, pathology)
  • Glycoproteins (physiology)
  • Immunoenzyme Techniques
  • Interleukin-6 (metabolism)
  • Intestinal Mucosa (metabolism, microbiology, pathology)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B (metabolism)
  • Phosphorylation
  • STAT3 Transcription Factor (metabolism)
  • Salmonella Infections, Animal (metabolism, microbiology, pathology)
  • Salmonella typhimurium (pathogenicity)
  • Signal Transduction

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