Abstract
Background: A 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced murine colitis model was developed to investigate the pathogenesis and to evaluate a method of treating human Crohn’s disease. This experimental model rapidly induces colitis similar to human Crohn’s disease lesion in a reproducible manner. However, natural exposure of the human digestive tract to TNBS is unrealistic. A novel animal model based on realistic data is eagerly anticipated in future research on pathogenesis of CD. Method: We evaluated the potency of Map antigen molecules in an effort to develop a novel colitis model using a more realistic source than TNBS. We prepared the Map antigen by ethanol extraction and developed a mouse model in a manner similar to that of the well-known TNBS-induced colitis in mice. In the experiment, seven days after subcutaneous (SC) injection of the antigen into normal C57BL/6 mice, the same antigen in 50% ethanol was injected into the colon by the transanal route with a fine cannula. Results: On the fifth day after the transanal injection, histopathological examination revealed full-thickness necrotizing colitis with erosion and ulcers; severe infiltration with neutrophils, lymphocytes, macrophages, and perforation. However, no change was detected with each single Map-antigen injection. Conclusion: The present results provide a novel animal model for research on CD and may be the key to clarifying the relationship between CD and Map. This is the first evidence that mycobacterium antigen induces necrotizing colitis.
Highlights
A 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced murine colitis model was developed to investigate the pathogenesis and to evaluate a method of treating human Crohn’s disease
All sections were stained with hematoxylin and eosin (H&E), and the magnification of photos is indicated as a bar
The present study provides the first evidence that the Mycobacterium avium subsp. paratuberculosis (Map) antigen has the potency to induce colitis that is very similar to mouse TNBS-induced colitis, which has been used as an experimental Crohn’s disease model (Arita et al 2005; Neurath et al 2000; te Velde et al 2006)
Summary
A 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced murine colitis model was developed to investigate the pathogenesis and to evaluate a method of treating human Crohn’s disease. This experimental model rapidly induces colitis similar to human Crohn’s disease lesion in a reproducible manner. An additional mystery is the “invisible Map” that supposedly grows in CD lesions (Momotani et al 2012; Pierce 2009; Van Kruiningen 1999) This phenomenon has been explained by isolation of a cell-wall-deficient, spheroplastic form of Map from human CD lesions (Wall et al 1993). Intestinal lesions in Ptb of cynomolgus were very similar to those of bovine but differed histopathologically from human CD (McClure et al 1987)
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