Angiogenesis blockade as a new therapeutic approach to experimental colitis

Danese, Silvio; Sans, Miquel; Spencer, David M.; Beck, Ivy; Doñate, Fernando; Plunkett, Marian L.; De La Matte, Carol; Redline, Raymond; Shaw, David E.; Levine, Alan D.; Mozar, Andrew P.; Fiocchi, Claudio
June 2007
Gut;Jun2007, Vol. 56 Issue 6, p855
Academic Journal
Background: Neoangiogenesis is a critical component of chronic inflammatory disorders. Inhibition of angiogenesis is an effective treatment in animal models of inflammation, but has not been tested in experimental colitis. Aim: To investigate the effect of ATN-161, an anti-angiogenic compound, on the course of experimental murine colitis. Method: Interleukin 10-deficient (IL10-/-) mice and wild-type mice were kept in ultra-barrier facilities (UBF) or conventional housing, and used for experimental conditions. Dextran sodium sulphate (DSS)-treated mice were used as a model of acute colitis. Mice were treated with ATN-161 or its scrambled peptide ATN-163. Mucosal neoangiogenesis and mean vascular density (MVD) were assessed by CD31 staining. A Disease Activity Index (DAI) was determined, and the severity of colitis was determined by a histological score. Colonic cytokine production was measured by ELISA, and lamina propria mononuclear cell proliferation by thymidine incorporation. Result MVD increased in parallel with disease progression in IL10-/- mice kept in conventional housing, but not in IL10-/- mice kept in UBF. Angiogenesis also occurred in DSS-treated animals. 1L10-/- mice with established disease treated with ATN-161, but not with ATN-163, showed a significant and progressive decrease in DAI. The histological colitis score was significantly lower in ATN-161 -treated mice than in scrambled peptide-treated mice. Inhibition of angiogenesis was confirmed by a significant decrease of MYD in ATN-1 61-treated mice than in ATN-163-treated mice. No therapeutic effects were observed in the DSS model of colitis. ATN-161 showed no direct immunomodulatory activity in vitro. Conclusion: Active angiogenesis occurs in the gut of IL10-/- and DSS-treated colitic mice and parallels disease progression. ATN-161 effectively decreases angiogenesis as well as clinical severity and histological inflammation in IL10-/- mice but not in the DDS model of inflammatory bowel disease (IBD). The results provide the rational basis for considering anti-angiogenic strategies in the treatment of IBD in humans.


Related Articles

  • Suppression of interleukin-1ß- and tumor necrosis factor-·-induced inflammatory responses by leukocytapheresis therapy in patients with ulcerative colitis. Andoh, Akira; Ogawa, Atsuhiro; Kitamura, Ken-ichi; Inatomi, Osamu; Fujino, Sanae; Tsujikawa, Tomoyuki; Sasaki, Masaya; Mitsuyama, Keiichi; Fujiyama, Yoshihide // Journal of Gastroenterology;2004, Vol. 39 Issue 12, p1150 

    Background. To elucidate the molecular mechanisms involved in the therapeutic effects of leukocytapheresis (LCAP), we investigated the alterations in the cytokine responses of peripheral blood mononuclear cells (PBMCs) before and after LCAP therapy in ulcerative colitis (UC) patients....

  • Lysate of Probiotic Lactobacillus casei DN-114 001 Ameliorates Colitis by Strengthening the Gut Barrier Function and Changing the Gut Microenvironment. Zakostelska, Zuzana; Kverka, Miloslav; Klimesova, Klara; Rossmann, Pavel; Mrazek, Jakub; Kopecny, Jan; Hornova, Michaela; Srutkova, Dagmar; Hudcovic, Tomas; Ridl, Jakub; Tlaskalova-Hogenova, Helena // PLoS ONE;2011, Vol. 6 Issue 11, p1 

    Background: Probiotic bacteria can be used for the prevention and treatment of human inflammatory diseases including inflammatory bowel diseases (IBD). However, the nature of active components and exact mechanisms of this beneficial effects have not been fully elucidated. Our aim was to...

  • Evidence for non-neutralizing autoantibodies against IL-10 signalling components in patients with inflammatory bowel disease. Frede, Natalie; Glocker, Erik-Oliver; Wanders, Jennifer; Engelhardt, Karin R.; Kreisel, Wolfgang; Ruemmele, Frank M.; Grimbacher, Bodo // BMC Immunology;2014, Vol. 15 Issue 1, p1 

    Background Inflammatory bowel disease constitutes a heterogeneous group of conditions, whose aetiology is only partly understood. The prevailing hypothesis on its pathogenesis is that IBD is the result of an inadequate immune response to the resident bacterial flora of the intestine. An...

  • High Levels of Proinflammatory Cytokines, but Not Markers of Tissue Injury, in Unaffected Intestinal Areas from Patients with IBD. León, Alberto J.; Gómez, Emma; Garrote, Jose A.; Bernardo, David; Barrera, Asterio; Marcos, Jose L.; Fernández-Salazar, Luis; Velayos, Benito; Blanco-Quirós, Alfredo; Arranz, Eduardo // Mediators of Inflammation;2009, Vol. 2009, Special section p1 

    Intestinal alterations in IBD are triggered and maintained by an overexpression of proinflammatory cytokines. Additionally, increased immune activation has been found in the adjacent intestinal areas without displaying any apparent histological alterations, however, the regulatory environment is...

  • Huang Qi Jian Zhong Pellet Attenuates TNBS-Induced Colitis in Rats via Mechanisms Involving Improvement of Energy Metabolism. Duan-Yong Liu; Chun-Shui Pan; Yu-Ying Liu; Xiao-Hong Wei; Chang-Man Zhou; Kai Sun; Ke He; Chong Li; Li Yan; Jing-Yu Fan; Chuan-She Wang; Toshifumi Hibi; Hong-Ning Liu; Jing-Yan Han // Evidence-based Complementary & Alternative Medicine (eCAM);2013, Vol. 2013, p1 

    Huang Qi Jian Zhong Pellet (HQJZ) is a famous Chinese medicine formula for treatment of various gastrointestinal tract diseases. This study investigated the role of HQJZ in 2,4,6-trinitrobenzene sulfonic acid- (TNBS-) induced colitis and its underlying mechanism. Colonic mucosal injury was...

  • Increased aggregation response of platelets in patients with inflammatory bowel disease. Andoh, Akira; Yoshida, Takashi; Yagi, Yuki; Bamba, Shigeki; Hata, Kazunori; Tsujikawa, Tomoyuki; Kitoh, Katsuyuki; Sasaki, Masaya; Fujiyama, Yoshihide // Journal of Gastroenterology;Jan2006, Vol. 41 Issue 1, p47 

    Background. Platelets play an important role in hemostatic and inflammatory responses. To evaluate any potential enhancement of platelet activity in patients with inflammatory bowel disease (IBD), we measured the platelet aggregation responses to various stimuli. Methods. Twenty-two healthy...

  • The temporal evolution of antidrug antibodies in patients with inflammatory bowel disease treated with infliximab. Ungar, Bella; Chowers, Yehuda; Yavzori, Miri; Picard, Orit; Fudim, Ella; Har-Noy, Ofir; Kopylov, Uri; Eliakim, Rami; Ben-Horin, Shomron // Gut;Aug2014, Vol. 63 Issue 8, p1258 

    Objective To characterise the temporal evolution of antibodies to infliximab (ATI). Design Prospective observational study of infliximabtreated patients with inflammatory bowel disease between 2009 and 2012. Interventions Trough levels of infliximab and ATI were measured before each infusion by...

  • Clinical value of fecal calprotectin in determining diseaseactivity of ulcerative colitis. Jun-Ying Xiang; Qin Ouyang; Guo-Dong Li; Nan-Ping Xiao // World Journal of Gastroenterology;1/7/2008, Vol. 14 Issue 1, p53 

    AIM: To investigate possibility and clinical application of fecal calprotectin in determining disease activity of ulcerative colitis (UC). METHODS: The enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of calprotectin in feces obtained from 66 patients with UC and...

  • Target Antigens for Perinuclear Antineutrophil Cytoplasmic Antibodies in Iranian Patients with Ulcerative Colitis. Bahari, Ali; Aarabi, Mahmoud; Hedayati, Mehdi; Jarollahi, Ali; Firouzi, Farzad; Aghazadeh, Rahim; Zali, Mohammad Reza; Bari, Zohreh; Hashemi, Mohammad; Esmaeilzadeh, Abbas; Mokhtarifar, Ali; Ganji, Azita // Middle East Journal of Digestive Diseases;2014, Vol. 6 Issue 4, p9 

    BACKGROUND Patients with ulcerative colitis (UC) carry autoantibodies such as perinuclear antineutrophil cytoplasmic antibodies (p-ANCA). Objective: The aim of the present study was to evaluate the target antigens for p-ANCA in Iranian patients with UC. METHODS p-ANCA target antigens including...


Read the Article


Sign out of this library

Other Topics