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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

Hematoxylin-stained colon sections of mice treated with DSS at 0, 1, 3, 5, 9 (withdraw after 5 days treatment, 4 days to recover) and 14 (withdraw after 5 days treatment, 9 days to recover) days, with magnification of 20 times.(A): Distal colon; (B) Proximal colon.
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pone-0006073-g003: Hematoxylin-stained colon sections of mice treated with DSS at 0, 1, 3, 5, 9 (withdraw after 5 days treatment, 4 days to recover) and 14 (withdraw after 5 days treatment, 9 days to recover) days, with magnification of 20 times.(A): Distal colon; (B) Proximal colon.

Mentions: Control mouse colon sections (Fig. 3, 0 day) showed the intact epithelium, well defined crypt length, and no edema neutrophil infiltration in mucosa and submucosa, and no ulcers or erosions. In contrast, colon tissue from DSS treated mice showed increasingly severe inflammatory lesions extensively throughout the mucosa during the DSS treatment (Fig. 3 1-, 3-, 5-day), then attenuating inflammatory lesions throughout the mucosa after DSS withdrawal. Ulcers, shortening and loss of crypts were seen focally at the beginning progressing to more extensive areas of mucosal involvement and finallythe whole colon (Fig. 3 1-, 3-, 5-day), which are in agreement with the data described previously [17], [18], then the mucosa were recovered to almost intact after DSS withdrawal (Fig. 3 9-, 14-day). Submucosal edema increased during DSS treatment 1-, 3-, 5-day group (Fig. 3) and recovered to normal state at day 9 and day 14 (Fig. 3); Infiltration of immune cells including neutrophils and lymphocytes were seen in the lamina propria in DSS treated mice (Fig. 3 1-, 3-, 5-day), and cleared after the DSS withdrawal in 9- and 14-day group.


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)

Hematoxylin-stained colon sections of mice treated with DSS at 0, 1, 3, 5, 9 (withdraw after 5 days treatment, 4 days to recover) and 14 (withdraw after 5 days treatment, 9 days to recover) days, with magnification of 20 times.(A): Distal colon; (B) Proximal colon.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0006073-g003: Hematoxylin-stained colon sections of mice treated with DSS at 0, 1, 3, 5, 9 (withdraw after 5 days treatment, 4 days to recover) and 14 (withdraw after 5 days treatment, 9 days to recover) days, with magnification of 20 times.(A): Distal colon; (B) Proximal colon.
Mentions: Control mouse colon sections (Fig. 3, 0 day) showed the intact epithelium, well defined crypt length, and no edema neutrophil infiltration in mucosa and submucosa, and no ulcers or erosions. In contrast, colon tissue from DSS treated mice showed increasingly severe inflammatory lesions extensively throughout the mucosa during the DSS treatment (Fig. 3 1-, 3-, 5-day), then attenuating inflammatory lesions throughout the mucosa after DSS withdrawal. Ulcers, shortening and loss of crypts were seen focally at the beginning progressing to more extensive areas of mucosal involvement and finallythe whole colon (Fig. 3 1-, 3-, 5-day), which are in agreement with the data described previously [17], [18], then the mucosa were recovered to almost intact after DSS withdrawal (Fig. 3 9-, 14-day). Submucosal edema increased during DSS treatment 1-, 3-, 5-day group (Fig. 3) and recovered to normal state at day 9 and day 14 (Fig. 3); Infiltration of immune cells including neutrophils and lymphocytes were seen in the lamina propria in DSS treated mice (Fig. 3 1-, 3-, 5-day), and cleared after the DSS withdrawal in 9- and 14-day group.

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