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Axin1 prevents Salmonella invasiveness and inflammatory response in intestinal epithelial cells.

BACKGROUND: Axin1 and its homolog Axin2 are scaffold proteins essential for regulating Wnt signaling. Axin-dependent regulation of Wnt is important for various developmental processes and human diseases. However, the involvement of Axin1 and Axin2 in host defense and inflammation remains to be determined. METHODS/PRINCIPAL FINDINGS: Here, we report that Axin1, but not Axin2, plays an essential role in host-pathogen interaction mediated by the Wnt pathway. Pathogenic Salmonella colonization greatly reduces the level of Axin1 in intestinal epithelial cells. This reduction is regulated at the posttranslational level in early onset of the bacterial infection. Further analysis reveals that the DIX domain and Ser614 of Axin1 are necessary for the Salmonella-mediated modulation through ubiquitination and SUMOylation. CONCLUSION/SIGNIFICANCE: Axin1 apparently has a preventive effect on bacterial invasiveness and inflammatory response during the early stages of infection. The results suggest a distinct biological function of Axin1 and Axin2 in infectious disease and intestinal inflammation while they are functionally equivalent in developmental settings.

Pubmed ID: 22509369

Authors

  • Zhang YG
  • Wu S
  • Xia Y
  • Chen D
  • Petrof EO
  • Claud EC
  • Hsu W
  • Sun J

Journal

PloS one

Publication Data

April 17, 2012

Associated Grants

  • Agency: NIDDK NIH HHS, Id: 1R03DK089010-01
  • Agency: NCI NIH HHS, Id: CA106308
  • Agency: NIDCR NIH HHS, Id: DE015654
  • Agency: NIDDK NIH HHS, Id: KO1 DK075386
  • Agency: NIAMS NIH HHS, Id: R01 AR055915
  • Agency: NCI NIH HHS, Id: R01 CA106308
  • Agency: NIDCR NIH HHS, Id: R01 DE015654

Mesh Terms

  • Animals
  • Axin Protein
  • Caco-2 Cells
  • Disease Models, Animal
  • Epithelial Cells
  • Gene Expression
  • HCT116 Cells
  • HT29 Cells
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate
  • Inflammation
  • Mice
  • Mice, Inbred C57BL
  • Salmonella
  • Salmonella Infections
  • Ubiquitination
  • Wnt Signaling Pathway
  • beta Catenin