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Updated: May 31, 2026
DNBS/TNBS Colitis Models: Providing Insights Into Inflammatory Bowel Disease and Effects of Dietary Fat
Published on: February 27, 2014
Overexpression of Ste20-related proline/alanine-rich kinase exacerbates experimental colitis in mice
Yutao Yan1, Hamed Laroui, Sarah A Ingersoll
1Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. yyan2@emory.edu
Abstract:
Inflammatory bowel disease, mainly Crohn's disease and ulcerative colitis, are characterized by epithelial barrier disruption and altered immune regulation. Colonic Ste20-like proline/alanine-rich kinase (SPAK) plays a role in intestinal inflammation, but its underlying mechanisms need to be defined. Both SPAK-transfected Caco2-BBE cells and villin-SPAK transgenic (TG) FVB/6 mice exhibited loss of intestinal barrier function. Further studies demonstrated that SPAK significantly increased paracellular intestinal permeability to FITC-dextran. In vivo studies using the mouse models of colitis induced by dextran sulfate sodium (DSS) and trinitrobenzene sulfonic acid showed that TG FVB/6 mice were more susceptible to DSS and trinitrobenzene sulfonic acid treatment than wild-type FVB/6 mice, as demonstrated by clinical and histological characteristics and enzymatic activities. Consistent with this notion, we found that SPAK increased intestinal epithelial permeability, which likely facilitated the production of inflammatory cytokines in vitro and in vivo, aggravated bacterial translocation in TG mice under DSS treatment, and consequently established a context favorable for the triggering of intestinal inflammation cascades. In conclusion, overexpression of SPAK inhibits maintenance of intestinal mucosal innate immune homeostasis, which makes regulation of SPAK important to attenuate pathological responses in inflammatory bowel disease.
Insights
Ste20-like proline/alanine-rich kinase (SPAK) overexpression disrupts the intestinal barrier, increasing permeability and susceptibility to inflammatory bowel disease. Regulating SPAK is crucial for managing intestinal inflammation and restoring immune homeostasis.
Area of Science:
- Gastroenterology
- Immunology
- Molecular Biology
Background:
- Inflammatory bowel disease (IBD) involves epithelial barrier defects and immune dysregulation.
- The role of colonic Ste20-like proline/alanine-rich kinase (SPAK) in intestinal inflammation requires further elucidation.
Purpose of the Study:
- To investigate the role of SPAK in maintaining intestinal barrier function and its impact on inflammatory bowel disease pathogenesis.
- To define the mechanisms by which SPAK influences intestinal permeability and inflammation.
Main Methods:
- Utilized SPAK-transfected Caco2-BBE cells and villin-SPAK transgenic (TG) mice.
- Assessed intestinal barrier function using FITC-dextran permeability assays.
- Induced colitis in TG and wild-type mice using dextran sulfate sodium (DSS) and trinitrobenzene sulfonic acid (TNBS).
- Evaluated clinical, histological, and enzymatic markers of inflammation.
Main Results:
- SPAK overexpression in cells and TG mice led to significant loss of intestinal barrier function and increased paracellular permeability.
- TG mice exhibited heightened susceptibility to DSS- and TNBS-induced colitis.
- SPAK promoted inflammatory cytokine production and aggravated bacterial translocation in TG mice during DSS treatment.
Conclusions:
- SPAK overexpression compromises intestinal epithelial barrier integrity, exacerbating inflammatory responses.
- SPAK dysregulation contributes to the development and severity of inflammatory bowel disease.
- Targeting SPAK may offer a therapeutic strategy for attenuating pathological responses in IBD.
