Thalidomide impairment of trinitrobenzene sulphonic acid‐induced colitis in the rat–role of endothelial cell‐leukocyte interaction

Lienenlüke, Bianca; Stojanović, Tomislav; Fiebig, Thomas; Fayyazi, Afshin; Germann, Tieno; Hecker, Markus

doi:10.1038/sj.bjp.0704193

Cited by 27 publications

(31 citation statements)

References 38 publications

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“…31 The activation of NF-B, an important mediator of inflammation, cell proliferation, and restenosis, 34,35 was also found to be blocked with thalidomide because of its inhibitory effect on I-B degradation. 36 All these effects of thalidomide may be beneficial in the prevention of neointimal hyperplasia.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the aforementioned effects, thalidomide has been reported to reduce the synthesis of other proinflammatory cytokines, such as IL-1, IL-6, and IL-8, 11 and the expression of endothelial adhesion molecules, including integrin, intercellular adhesion molecule, and vascular cell adhesion molecule; [31][32][33] as a consequence, the interactions between endothelial cells and circulating leukocytes are inhibited. 31 The activation of NF-B, an important mediator of inflammation, cell proliferation, and restenosis, 34,35 was also found to be blocked with thalidomide because of its inhibitory effect on I-B degradation.…”

Section: Discussionmentioning

confidence: 99%

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Thalidomide as a Potent Inhibitor of Neointimal Hyperplasia After Balloon Injury in Rat Carotid Artery

Park

Kim

Yang

et al. 2004

ATVB

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Objective-Inflammation is one of the main pathogeneses of neointimal hyperplasia after coronary intervention.Thalidomide, because of its potent antiinflammatory and immunomodulatory properties, is being re-evaluated in several clinical fields. Therefore, we examined whether thalidomide therapy affects neointimal formation. Methods and Results-In male Sprague-Dawley rats, 100 mg/kg of either thalidomide or sucrose (control) was administered daily from 3 days before injury to 2 weeks after conventional carotid artery denudation injury. Thalidomide administration resulted in a significant reduction of neointimal formation (neointima to media ratio 1.26Ϯ0.29 versus 0.35Ϯ0.13, PϽ0.001) and proliferative activity of vascular smooth muscle cells. In addition, arterial macrophage infiltration and local expressions of tumor necrosis factor alpha (TNF-␣) and basic fibroblast growth factor (bFGF) in the injured arteries as measured by immunohistochemistry and immunoblot analysis were significantly reduced by thalidomide treatment. Serum TNF-␣, measured by ELISA, was also significantly reduced in the thalidomide-treated animals compared with controls after injury (856Ϯ213 versus 449Ϯ68 pg/mL on day 3, Pϭ0.001; 129Ϯ34 versus 63Ϯ18 pg/mL on day 14, Pϭ0.001), and we observed a good positive correlation between the serum TNF-␣ levels and the severity of neointimal growth. Conclusions-We found that thalidomide, through its antiinflammatory and antiproliferative effects, significantly inhibits neointimal hyperplasia in balloon-injured rat carotid arteries. Our results suggest a potential role of thalidomide as a potent inhibitor of neointimal formation after angioplasty.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Thalidomide as a Potent Inhibitor of Neointimal Hyperplasia After Balloon Injury in Rat Carotid Artery

Park

Kim

Yang

et al. 2004

ATVB

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“…In addition, VEGF was recently found to induce the expression of adhesion molecules such as intercellular adhesion molecule-1 [47] , and also to increase the adhesion of immune cells to the colonic endothelium [48] . On the other hand, thalidomide and its analogue supidimide, significantly attenuated TNBSinduced colitis, impairing adhesion of leukocytes to vascular endothelial cells and reducing the vascular cell adhesion molecule-1 mRNA expression [26] . Therefore, it is likely that VEGF may play a role as intermediary molecule acting in the interface between angiogenic and chronic inflammation in IBD.…”

Section: A C Bmentioning

confidence: 99%

“…For adhesions grading was considered: 0, absent; 1, light; 2, multiple; for strictures 0, absent; 1, light; 3 accentuated with proximal dilatation. For ulcer grading the scoring was 0, absent; 1, linear ulcer < 1 cm; 2, two linear ulcers < 1 cm; 3, numerous ulcers > 1 cm; and for thickness of the colon wall, 0, < 1 mm; 1, 1 to 3 mm; 2, > 3 mm; total score ranging from 0 to 10 [26] .…”

Section: Macroscopic Assessment Of the Colonmentioning

confidence: 99%

Therapeutic and prophylactic thalidomide in TNBS-induced colitis: Synergistic effects on TNF-α, IL-12 and VEGF production

Carvalho

Souza²,

Carneiro³

et al. 2007

WJG

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AIM:To evaluated the therapeutic and prophylactic effect of thalidomide on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Thalidomide has been reported to downregulate the expression of tumor necrosis factor α (TNF-α), IL-12, and vascular endothelial growth factor (VEGF), hallmarks of intestinal inflammation in Crohn's disease (CD). METHODS:Male Wistar rats were divided in five groups of ten animals each. Four groups received a rectal infusion of TNBS in ethanol. The first group was sacrificed 7 d after colitis induction. The second and third groups received either thalidomide or placebo by gavage and were sacrificed at 14 d. The fourth group received thalidomide 6 h before TNBS administration, and was sacrificed 7 d after induction. The fifth group acted as the control group and colitis was not induced. Histological inflammatory scores of the colon were performed and lamina propria CD4+ T cells, macrophages, and VEGF+ cells were detected by immunohistochemistry. TNF-α and IL-12 were quantified in the supernatant of organ cultures by ELISA. RESULTS:Significant reduction in the inflammatory score and in the percentage of VEGF+ cells was observed in the group treated with thalidomide compared with animals not treated with thalidomide. Both TNF-α and IL-12 levels were significantly reduced among TNBS induced colitis animals treated with thalidomide compared with animals that did not receive thalidomide. TNF-α levels were also significantly reduced among the animals receiving thalidomide prophylaxis compared with untreated animals with TNBS-induced colitis. Intestinal levels of TNF-α and IL-12 were significantly correlated with the inflammatory score and the number of VEGF+ cells. CONCLUSION:Thalidomide significantly attenuates TNBS-induced colitis by inhibiting the intestinal production of TNF-α, IL-12, and VEGF. This effect may support the use of thalidomide as an alternate approach in selected patients with CD.

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“…The animals have diarrhea and a large weight loss. Other study groups report increased leukocyte-endothelium interaction with the colitis model [62].…”

Section: Discussionmentioning

confidence: 98%

Endothelin-1 Receptor Antagonist (LU-135252) Improves the Microcirculation and Course of TNBS Colitis in Rats

et al. 2006

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The role of microcirculation in the pathogenesis and course of chronic inflammatory bowel disease is still unclear. The aim of this study was the evaluation of the role of microcirculation in colitis activity in the rat TNBS (trinitrobenzenesulfonic acid) colitis model using endothelin-1 and a selective endothelin-1 receptor antagonist (LU-135252). Target parameters were capillary blood flow, functional capillary density, vascular permeability, and leukocyte sticking as well as recording of hematocrit, weight course, diuresis, stool quality, and degree of inflammation using a histological colitis score. The acute phase of TNBS colitis is characterized by an extensive disturbance of microcirculation (a significant decrease in capillary blood flow and capillary density and a significant increase in capillary permeability and leukocyte sticking in the mucosa). There is also a significant increase in hematocrit and a significant decrease in diuresis and weight. An exogenous supply of endothelin-1 does not lead to an aggravation of these disorders because of a possible blockage of the endothelin-1 receptors by endogenous endothelin-1 in this florid inflammatory phase. Applying the selective endothelin-1 receptor A antagonist LU-135252 leads to a significant improvement of all microcirculatory parameters and clinical findings compared to the untreated colitis group. Direct improvement of capillary blood flow in the early phase of colitis leads to reduced colitis activity, which underscores the pathogenetic role of the microcirculation in the progression of colitis.

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Thalidomide impairment of trinitrobenzene sulphonic acid‐induced colitis in the rat–role of endothelial cell‐leukocyte interaction

Cited by 27 publications

References 38 publications

Thalidomide as a Potent Inhibitor of Neointimal Hyperplasia After Balloon Injury in Rat Carotid Artery

Thalidomide as a Potent Inhibitor of Neointimal Hyperplasia After Balloon Injury in Rat Carotid Artery

Therapeutic and prophylactic thalidomide in TNBS-induced colitis: Synergistic effects on TNF-α, IL-12 and VEGF production

Endothelin-1 Receptor Antagonist (LU-135252) Improves the Microcirculation and Course of TNBS Colitis in Rats

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