Chitinase 3-like 1 synergistically activates IL6-mediated STAT3 phosphorylation in intestinal epithelial cells in murine models of infectious colitis.
BACKGROUND
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.
*Gastrointestinal Unit and †Center for the Study of Inflammatory Bowel Disease, Department of Medicine, ‡Molecular Pathology Unit, Department of Pathology, and §Division of Mucosal Immunology, Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and ‖Section of Pulmonary and Critical Care Medicine, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
Hoa T
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Tran
In-Ah
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Lee
Daren
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Low
Alan
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Kamba
Atsushi
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Mizoguchi
Hai N
HN
Shi
Chun G
CG
Lee
Jack A
JA
Elias
Emiko
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Mizoguchi
D000818:Animals; D001422:Bacterial Adhesion; D015153:Blotting, Western; D002478:Cells, Cultured; D000071451:Chitinase-3-Like Protein 1; D003092:Colitis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D004926:Escherichia coli / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D006023:Glycoproteins / Q000502:physiology*; D007124:Immunoenzyme Techniques; D015850:Interleukin-6 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012481:Salmonella Infections, Animal / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D012486:Salmonella typhimurium / Q000472:pathogenicity; D015398:Signal Transduction
C509289:Chil1 protein, mouse; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D015850:Interleukin-6; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse