Temporal and spatial analysis of clinical and molecular parameters in dextran sodium sulfate induced colitis

PLoS One. 2009 Jun 29;4(6):e6073. doi: 10.1371/journal.pone.0006073.

Abstract

Background: Inflammatory bowel diseases (IBD), including mainly ulcerative colitis (UC) and Crohn's disease (CD), are inflammatory disorders of the gastrointestinal tract caused by an interplay of genetic and environmental factors. Murine colitis model induced by Dextran Sulfate Sodium (DSS) is an animal model of IBD that is commonly used to address the pathogenesis of IBD as well as to test efficacy of therapies. In this study we systematically analyzed clinical parameters, histological changes, intestinal barrier properties and cytokine profile during the colitic and recovery phase.

Methods: C57BL/6 mice were administered with 3.5% of DSS in drinking water for various times. Clinical and histological features were determined using standard criteria. Myeloperoxidase (MPO) activity, transepithelial permeability and proinflammatory mediators were determined in whole colon or proximal and distal parts of colon.

Results: As expected after administration of DSS, mice manifest loss of body weight, shortening of colon length and bloody feces. Histological manifestations included shortening and loss of crypts, infiltration of lymphocytes and neutrophil, symptoms attenuated after DSS withdrawal. The MPO value, as inflammation indicator, also increases significantly at all periods of DSS treatment, and even after DSS withdrawal, it still held at very high levels. Trans-mucosal permeability increased during DSS treatment, but recovered to almost control level after DSS withdrawal. The production of proinflammatory mediators by colonic mucosa were enhanced during DSS treatment, and then recovered to pre-treated level after DSS withdrawal. Finally, enhanced expression of proinflammatory mediators also revealed a different profile feature in proximal and distal parts of the colon.

Conclusion: Experimental colitis induced by DSS is a good animal model to study the mechanisms underlying the pathogenesis and intervention against IBD, especially UC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Colitis / chemically induced*
  • Colitis / drug therapy
  • Colitis / microbiology
  • Colitis / physiopathology*
  • Colon / pathology
  • Cytokines / metabolism
  • Dextran Sulfate / pharmacology*
  • Disease Models, Animal
  • Inflammation
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Permeability
  • Peroxidase / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors

Substances

  • Cytokines
  • Dextran Sulfate
  • Peroxidase