Hapten-induced chronic colitis in the rat: Alternatives to trinitrobenzene sulfonic acid

Wallace, John L.; Le, Tai; Carter, Lisa; Appleyard, Caroline B.; Beck, Paul L.

doi:10.1016/1056-8719(95)00001-x

Cited by 85 publications

(56 citation statements)

References 6 publications

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“…Because NEPϪ/Ϫ mice are sensitive to endotoxic shock (17), we induced colitis with a very low dose of DNBS (4 mg per mouse) by using a modification (18) of the method first described in rats (19). In preliminary experiments, this dose of DNBS was found to induce reproducible colitis without mortality.…”

Section: Methodsmentioning

confidence: 99%

Neutral endopeptidase (EC 3.4.24.11) terminates colitis by degrading substance P

Sturiale

Barbara

Qiu

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

162

112

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Neurogenic inf lammation is regulated by sensory nerves and characterized by extravasation of plasma proteins and infiltration of neutrophils from post-capillary venules and arteriolar vasodilatation. Although it is well established that substance P (SP) interacts with the neurokinin 1 receptor (NK1R) to initiate neurogenic inf lammation, the mechanisms that terminate inf lammation are unknown. We examined whether neutral endopeptidase (NEP), a cellsurface enzyme that degrades SP in the extracellular f luid, terminates neurogenic inf lammation in the colon. In NEP knockout mice, the SP concentration in the colon was Ϸ2.5-fold higher than in wild-type mice, suggesting increased bioavailability of SP. The extravasation of Evans blue-labeled plasma proteins in the colon of knockout mice under basal conditions was Ϸ4-fold higher than in wild-type mice. This elevated plasma leak was attenuated by recombinant NEP or the NK1R antagonist SR140333, and is thus caused by diminished degradation of SP. To determine whether deletion of NEP predisposes mice to uncontrolled inf lammation, we compared dinitrobenzene sulfonic acid-induced colitis in wild-type and knockout mice. The severity of colitis, determined by macroscopic and histologic scoring and by myeloperoxidase activity, was markedly worse in knockout than wild-type mice after 3 and 7 days. The exacerbated inf lammation in knockout mice was prevented by recombinant NEP and SR140333. Thus, NEP maintains low levels of SP in the extracellular f luid under basal conditions and terminates its proinf lammatory effects. Because we have previously shown that intestinal inf lammation results in down-regulation of NEP and diminished degradation of SP, our present results suggest that defects in NEP expression contribute to uncontrolled inf lammation.

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Section: Methodsmentioning

confidence: 99%

Neutral endopeptidase (EC 3.4.24.11) terminates colitis by degrading substance P

Sturiale

Barbara

Qiu

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

162

112

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“…intracolonic administration of 2,4-dinitrobenzene sulfonic acid (DNBS) dissolved in ethanol or saline, or ethanol alone. DNBS is related to TNBS and DNBS/ethanol induces an inflammation in the colon comparable to TNBS/ethanol [22]. To compare T cell activation in the colon following these various protocols, cytokine profiles were characterized by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry.…”

Section: Introductionmentioning

confidence: 99%

CD4+ T cells from 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rodents migrate to the recipient's colon upon transfer; down-regulation by CD8+ T cells

Palmen

Wijburg

Kunst

et al. 1998

Clinical and Experimental Immunology

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SUMMARYCD4 þ T cells play an important role in the aetiology of inflammatory bowel disease (IBD), but it is not clear which factor(s) cause activation of these cells. The aim of this study was to examine the effects of adoptive transfer of splenic (CD4 þ ) T cells from TNBS/ethanol-sensitized donor rats to naive recipients and the migration pattern of transferred T cells. For the transfer experiments, colitis was induced in rats by colonic administration of TNBS/ethanol. Seventeen days later, either total splenic T cells or CD4 þ , or CD8 þ T cells were transferred to naive recipients. At days 1, 2 and 3 after transfer, the recipients were killed and the migration pattern of the transferred T cells was studied, as well as inflammatory cells in several organs, including the colon. To determine cytokine profiles of the T cells, colitis was induced in mice. Therefore, different combinations of 2,4-dinitrobenzene sulfonic acid (DNBS) in ethanol or saline, or ethanol alone were intrarectally administered. At day 9 after induction of colitis, mice were killed and cytokine profiles in the colon were studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. The results show that CD4 þ T cells from donor rats with TNBS/ ethanol-induced colitis migrate in particular to the colon upon transfer to naive recipients, and that this process is down-regulated by CD8 þ T cells. This migration is probably caused by T cell recognition of the colonic bacterial flora and initiates an inflammatory reaction in the recipient's colon, characterized by an increase of the recipient's own T cells, macrophages, and neutrophils. In the mice experiments we showed that a second administration of DNBS/ethanol or ethanol alone, which presumably causes bacterial translocation, results in increased numbers of T cells into the colon, accompanied by an increase in Th1 cytokines. These data suggest that Th1 cells recognize the colonic bacterial flora.

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“…6 For this, 29 mg of DNBS was dissolved in 250 l of 50% ethanol and instilled into the colon 8 cm proximal to the anus with a PE50 catheter while the rat was under light anesthesia. Control and vehicle control groups received either 0.9% saline or 50% ethanol alone.…”

Section: Animalsmentioning

confidence: 99%

“…This is evidence of both an increase in cells which are normally innervated, as well as further evidence that inflammation can affect cells throughout the intestinal wall. Therefore, we used a model of chemically induced colitis in the rat 5,6 to study the effects of inflammation on neuronal number in the ENS, as well as axonal density within the smooth muscle. In addition, we have explored the potential for beneficial effects of topical application of the novel steroid budesonide of preserving intestinal innervation.…”

mentioning

confidence: 99%

Damage to the Enteric Nervous System in Experimental Colitis

Sanovic

Lamb

Blennerhassett

1999

The American Journal of Pathology

163

132

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Inflammation of the intestine causes pain and altered motility , at least in part through effects on the enteric nervous system. While these changes may be reversed with healing , permanent damage may contribute to inflammatory bowel disease (IBD) and post-enteritis irritable bowel syndrome. Since little information exists , we induced colitis in male Sprague-Dawley rats with dinitrobenzene sulfonic acid and used immunocytochemistry to examine the number and distribution of enteric neurons at times up to 35 days later. Inflammation caused significant neuronal loss in the inflamed region by 24 hours , with only 49% of neurons remaining by days 4 to 6 and thereafter , when inflammation had subsided. Eosinophils were found within the myenteric plexus at only at the earliest time points , despite a general infiltration of neutrophils into the muscle wall. While the number of myenteric ganglia remained constant , there was significant decrease in the number of ganglia in the submucosal plexus. Despite reduced neuronal number and hyperplasia of smooth muscle , the density of axons among the smooth muscle cells remained unchanged during and after inflammation. Intracolonic application of the topical steroid budesonide caused a dose-dependent prevention of neuronal loss , suggesting that evaluation of anti-inflammatory therapy in inflammatory bowel disease should include quantitative assessment of neural components. (Am J Pathol 1999, 155:1051-1057)Inflammatory bowel disease (IBD) is a chronic idiopathic inflammation of the intestine that affects an increasing percentage of the population in Western society, with the highest incidence among the younger population, for whom there are no specific or effective treatments. The broad acting anti-inflammatory agents in wide use have serious side effects of immune suppression, loss of bone calcium, and growth retardation. Therefore, a strong need exists for increased information about the cellular basis of this disease, as well as new pharmacological tools and improved methods of use.Studies of IBD have relied heavily on immunological approaches, relating activation of immune cells to the periodic exacerbation and remissions of disease. However, a particular challenge lies in understanding the long-term or permanent changes present in the intestine in IBD, which are evident even in the periods of remission between acute episodes. Recently, attention has been paid to the other cell types in the intestine that may acquire the ability to participate in inflammation or that are previously unexpected targets of inflammatory change.1 This has shown that nonimmune cells can participate directly in inflammation, as well as pointing out the potential for long-term alterations in cell structure and function that may predispose to repeated episodes of inflammation. Thus, intestinal smooth muscle has been shown to have the potential to present antigen to activated T cells and may also be a source of cytokines that can directly affect neural function. 1,2Most, if not all, aspects of normal...

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Hapten-induced chronic colitis in the rat: Alternatives to trinitrobenzene sulfonic acid

Cited by 85 publications

References 6 publications

Neutral endopeptidase (EC 3.4.24.11) terminates colitis by degrading substance P

Neutral endopeptidase (EC 3.4.24.11) terminates colitis by degrading substance P

CD4+ T cells from 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rodents migrate to the recipient's colon upon transfer; down-regulation by CD8+ T cells

Damage to the Enteric Nervous System in Experimental Colitis

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