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

Yan Y, Kolachala V, Dalmasso G, Nguyen H, Laroui H, Sitaraman SV, Merlin D - PLoS ONE (2009)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA. yyan2@emory.edu

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.

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Related in: MedlinePlus

Determination of MPO enzymatic activity as an index of neutrophils infiltration into the injured tissue.(A): Distal colon; (B): Proximal colon. Results are expressed as MPO mUnits per µg protein and represent mean±SEM of 3 determinations. * P<0.05, ** P<0.01.
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pone-0006073-g004: Determination of MPO enzymatic activity as an index of neutrophils infiltration into the injured tissue.(A): Distal colon; (B): Proximal colon. Results are expressed as MPO mUnits per µg protein and represent mean±SEM of 3 determinations. * P<0.05, ** P<0.01.

Mentions: We measured colonic myeloperoxidase (MPO) activity as an indicator of the extent of neutrophil infiltration into the mucosa. MPO values were significantly higher in DSS-treated groups than corresponding controls at all the periods studied. Fig. 4 shows the quantification in concentrations of this parameter in the experimental animals. We found that DSS-induced increases of MPO activity reached to the maximum level of 92±28 mUnits/ug protein at day-5 group, 6-fold higher than that of the controls (14±3.5 mUnits/ug). After DSS was replaced with drinking water, MPO levels remained significantly higher at 9-day group (6-times increase as that in 5-day group). In the 14-day group, the MPO level had declined significantly but still higher than water-drinking group (Fig. 4).


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

Yan Y, Kolachala V, Dalmasso G, Nguyen H, Laroui H, Sitaraman SV, Merlin D - PLoS ONE (2009)

Determination of MPO enzymatic activity as an index of neutrophils infiltration into the injured tissue.(A): Distal colon; (B): Proximal colon. Results are expressed as MPO mUnits per µg protein and represent mean±SEM of 3 determinations. * P<0.05, ** P<0.01.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2698136&req=5

pone-0006073-g004: Determination of MPO enzymatic activity as an index of neutrophils infiltration into the injured tissue.(A): Distal colon; (B): Proximal colon. Results are expressed as MPO mUnits per µg protein and represent mean±SEM of 3 determinations. * P<0.05, ** P<0.01.
Mentions: We measured colonic myeloperoxidase (MPO) activity as an indicator of the extent of neutrophil infiltration into the mucosa. MPO values were significantly higher in DSS-treated groups than corresponding controls at all the periods studied. Fig. 4 shows the quantification in concentrations of this parameter in the experimental animals. We found that DSS-induced increases of MPO activity reached to the maximum level of 92±28 mUnits/ug protein at day-5 group, 6-fold higher than that of the controls (14±3.5 mUnits/ug). After DSS was replaced with drinking water, MPO levels remained significantly higher at 9-day group (6-times increase as that in 5-day group). In the 14-day group, the MPO level had declined significantly but still higher than water-drinking group (Fig. 4).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA. yyan2@emory.edu

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.

Show MeSH
Related in: MedlinePlus