Bosentan, an endothelin receptor antagonist, reduces leucocyte adhesion and inflammation in a murine model of inflammatory bowel disease

Anthoni, Christoph; Mennigen, Rudolf; Rijcken, Emile; Laukötter, M; Spiegel, Hans‐Ullrich; Senninger, N.; Schürmann, G.; Krieglstein, C. F.

doi:10.1007/s00384-005-0015-3

Cited by 27 publications

(24 citation statements)

References 50 publications

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“…It is more likely that chronic treatment with bosentan suppresses a distinct ET A/B receptor mediated process that develops during CH. In this regard, it is interesting that bosentan acting via ET receptors is a potent anti-inflammatory drug (2,12,16). Indeed, multiple studies in other tissues have shown that ET peptides are multifunctional proinflammatory agents capable of initiating and promoting an immune response.…”

Section: Discussionmentioning

confidence: 97%

Effect of the endothelin receptor antagonist bosentan on chronic hypoxia-induced morphological and physiological changes in rat carotid body

Chen¹,

He²,

Liu³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Previous experiments have repeatedly demonstrated that exposure to chronic hypoxia (CH) elicits remarkable structural changes and chemosensory hypersensitivity in the mammalian carotid body. Moreover, recent studies have shown that CH upregulates the neuroactive peptide, endothelin (ET), in oxygen-sensitive type I cells. The present study examines the possible involvement of ET in adaptation by concurrently exposing rats to hypobaric CH (B(P) = 380 Torr) and bosentan, a potent nonpeptide antagonist that blocks ET(A) and ET(B) receptors. Carotid body weight indicated that 14 days of CH induced organ enlargement, a response that was blunted in bosentan-treated rats (CH: 2.54 +/- 0.19-fold increase; CH plus bosentan: 1.92 +/- 0.14-fold increase; P < 0.05). Morphometric studies revealed that bosentan substantially eliminated CH-induced hyperplasia of chemosensory cell lobules as well as expansion of the connective tissue matrix. Vascular dilation associated with CH was not altered by the drug. In untreated animals exposed to 3 days of CH, expression of proliferating cell nuclear antigen (PCNA), a marker of mitosis, was increased in lobules of oxygen-sensitive type I cells and in extralobular vascular and connective tissue cells. The incidence of PCNA expression was significantly (P < 0.05) reduced in bosentan-treated animals. In vitro assessments of carotid sinus nerve (CSN) activity showed that enhancement of basal and hypoxia-evoked chemosensory activity following 9 days of CH was significantly (P < 0.001) blunted by concurrent treatment with bosentan. Collectively, our data are consistent with the hypothesis that CH-induced adaptation in the carotid body is at least partially mediated by signaling pathways involving ET receptors.

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Section: Discussionmentioning

confidence: 97%

Effect of the endothelin receptor antagonist bosentan on chronic hypoxia-induced morphological and physiological changes in rat carotid body

Chen¹,

He²,

Liu³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…This observation provides insight into the mechanism of bosentan as an inhibitor of the inflammatory reaction. In a murine model of inflammatory bowel disease, the antiinflammatory effect of bosentan was investigated, and it was determined that bosentan reduced inflammation in this animal model (Anthoni et al, 2006). In another study, it was seen that prophylactic oral administration of bosentan reduced clinical inflammation in trinitrobenzene sulphonateinduced colitis in rats (Güllüoglu et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Effect of bosentan on the production of proinflammatory cytokines in a rat model of emphysema

Gamze

Mehmet²,

Deveci³

et al. 2007

Exp Mol Med

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Endothelin (ET) receptor antagonists have been developed to produce a reduction of ET related effects in various diseases, as well as in animal models of airway inflammation. We aimed to investigate the anti-inflammatory potential of bosentan on a rat model of emphysema. Thirty Wistar male rats were classified as control group (group 1), intratracheally (i.t.) instilled with saline, treated with vehicle solution; elastase group (group 2), i.t. instilled with porcine pancreatic elastase (PPE), treated with vehicle solution; and PPE+bosentan group (group 3), i.t. instilled with PPE, treated with bosentan. The levels of TNF-α, IL-1β, IL-6, and IL-8 in bronchoalveolar lavage fluid (BALF) and lung tissue, cell counts in BALF, and histologic analysis of all groups were evaluated. Neutrophile granulocytes (NG) and alveolar macrophages (AM) were increased more in group 2 than in group 1 (P ＜ 0.001, P = 0.04, respectively). Compared with group 2, neutrophil granulocyte (NG) and alveolar macrophages (AM) counts were decreased in group 3 (P ＜ 0.001). Histological examination confirmed a diffuse neutrophilic inflammation and irregular alveolar air space enlargement in group 2. Treatment with bosentan partially reduced the enlarged lung volumes. Compared with group 1, the BALF levels of TNF-α and IL-6, and the lung tissue levels of IL-1β, IL-6, and IL-8 were increased in group 2 (P = 0.028, P = 0.005, P = 0.001, P = 0.019, P ＜ 0.001, respectively). The TNF-α and IL-8 levels of BALF (P = 0.007, P = 0.001, respectively), and the TNF-α, IL-1β, IL-6, and the IL-8 levels of lung tissue (P = 0.031, P = 0.017, P = 0.007, P ＜ 0.001) were decreased in group 3 compared to group 2. In conclusion, bosentan decreased the inflammatory response by reducing numbers of inflammatory cells and proinflammatory cytokines.

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“…Three cycles were completed (30 days). This strategy leads to a reliable and reproducible chronic colitis (3,9).…”

Section: Methodsmentioning

confidence: 99%

Mechanisms underlying the anti-inflammatory actions of boswellic acid derivatives in experimental colitis

Anthoni

Laukoetter²,

Rijcken³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

106

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Bosentan, an endothelin receptor antagonist, reduces leucocyte adhesion and inflammation in a murine model of inflammatory bowel disease

Cited by 27 publications

References 50 publications

Effect of the endothelin receptor antagonist bosentan on chronic hypoxia-induced morphological and physiological changes in rat carotid body

Effect of the endothelin receptor antagonist bosentan on chronic hypoxia-induced morphological and physiological changes in rat carotid body

Effect of bosentan on the production of proinflammatory cytokines in a rat model of emphysema

Mechanisms underlying the anti-inflammatory actions of boswellic acid derivatives in experimental colitis

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