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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

Mouse body weight changes during DSS treatment.C57BL/6 mice were administered to 3.5% DSS by drinking water for indicated days. Body weight changes are depicted as means±SEM body weight changes in each group. * P<0.05, ** P<0.01.
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pone-0006073-g001: Mouse body weight changes during DSS treatment.C57BL/6 mice were administered to 3.5% DSS by drinking water for indicated days. Body weight changes are depicted as means±SEM body weight changes in each group. * P<0.05, ** P<0.01.

Mentions: We induced experimental colitis in C57BL/6 mice by adding 3.5% DSS to the drinking water for indicated days. DSS intake did not differ between the different groups of mice (data not shown). Mice showed different extent of diarrhea, more and grosser rectal bleeding as DSS treatment progressed, which suggested presence and development of inflammation. Specially, after 3-days of DSS treatment, more than 70% (17/24) of mice in 3-, 5-, 9- and 14-day treated groups had diarrhea and occult blood or gross blood in the feces, and these signs disappeared in part after DSS was withdrawn for 4 days (day 9) and complete after DSS withdrawal for 9 days (day 14). It has been pointed out that 2 (out of 6) mice in the 5-day DSS treatment group died after DSS withdrawal. During the period of DSS treatment, the weight loss was noticed after DSS administration under the indicated days. As shown in Fig. 1, 3-, and 5-day groups, body weight significantly decreased during the DSS-treatment, much lower than those in normal drinking water-treated mice. After DSS withdrawal, mouse body weight recovers gradually. Colon length was also measured to determine the severity of colitis. We found that DSS could lead to significant reduction of colon length during the treatment as described in Fig. 2. This colon length shortening became most severe in 5-day DSS-treated mice compared to drinking water mice colon (Fig. 2) with a reduction in colon length of around 30%. The reduction could be recovered after withdrawal of DSS, such as day 9 and day 14 groups. In general, the mice receiving DSS had a clinical disease activity score of 9.4±1.1 in 5-day group based on the score system established previously [17].


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)

Mouse body weight changes during DSS treatment.C57BL/6 mice were administered to 3.5% DSS by drinking water for indicated days. Body weight changes are depicted as means±SEM body weight changes in each group. * P<0.05, ** P<0.01.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0006073-g001: Mouse body weight changes during DSS treatment.C57BL/6 mice were administered to 3.5% DSS by drinking water for indicated days. Body weight changes are depicted as means±SEM body weight changes in each group. * P<0.05, ** P<0.01.
Mentions: We induced experimental colitis in C57BL/6 mice by adding 3.5% DSS to the drinking water for indicated days. DSS intake did not differ between the different groups of mice (data not shown). Mice showed different extent of diarrhea, more and grosser rectal bleeding as DSS treatment progressed, which suggested presence and development of inflammation. Specially, after 3-days of DSS treatment, more than 70% (17/24) of mice in 3-, 5-, 9- and 14-day treated groups had diarrhea and occult blood or gross blood in the feces, and these signs disappeared in part after DSS was withdrawn for 4 days (day 9) and complete after DSS withdrawal for 9 days (day 14). It has been pointed out that 2 (out of 6) mice in the 5-day DSS treatment group died after DSS withdrawal. During the period of DSS treatment, the weight loss was noticed after DSS administration under the indicated days. As shown in Fig. 1, 3-, and 5-day groups, body weight significantly decreased during the DSS-treatment, much lower than those in normal drinking water-treated mice. After DSS withdrawal, mouse body weight recovers gradually. Colon length was also measured to determine the severity of colitis. We found that DSS could lead to significant reduction of colon length during the treatment as described in Fig. 2. This colon length shortening became most severe in 5-day DSS-treated mice compared to drinking water mice colon (Fig. 2) with a reduction in colon length of around 30%. The reduction could be recovered after withdrawal of DSS, such as day 9 and day 14 groups. In general, the mice receiving DSS had a clinical disease activity score of 9.4±1.1 in 5-day group based on the score system established previously [17].

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