Therapeutic effects of vasoactive intestinal peptide in the trinitrobenzene sulfonic acid mice model of Crohn's disease

2003 ◽  
Vol 124 (4) ◽  
pp. 961-971 ◽  
Author(s):  
Catalina Abad ◽  
Carmen Martinez ◽  
Maria G. Juarranz ◽  
Alicia Arranz ◽  
Javier Leceta ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Vasoactive Intestinal Peptide ◽  
Sulfonic Acid ◽  
Trinitrobenzene Sulfonic Acid ◽  
Therapeutic Effects ◽  
Mice Model

scholarly journals Polyphenolic Maqui Extract as a Potential Nutraceutical to Treat TNBS-Induced Crohn’s Disease by the Regulation of Antioxidant and Anti-Inflammatory Pathways

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1752
Author(s):  
Tamara Ortiz ◽  
Federico Argüelles-Arias ◽  
Matilde Illanes ◽  
Josefa-María García-Montes ◽  
Elena Talero ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Body Weight Loss ◽  
Trinitrobenzene Sulfonic Acid ◽  
Therapeutic Effects ◽  
Transmural Inflammation ◽  
Microscopic Damage ◽  
Anti Inflammatory

Nutraceuticals include a wide variety of bioactive compounds, such as polyphenols, which have been highlighted for their remarkable health benefits. Specially, maqui berries have shown great antioxidant activity and anti-inflammatory effects on some inflammatory diseases. The objectives of the present study were to explore the therapeutic effects of maqui berries on acute-phase inflammation in Crohn’s disease. Balb/c mice were exposed to 2,4,6-trinitrobenzene sulfonic acid (TNBS) via intracolonic administration. Polyphenolic maqui extract (Ach) was administered orally daily for 4 days after TNBS induction (Curative Group), and for 7 days prior to the TNBS induction until sacrifice (Preventive Group). Our results showed that both preventive and curative Ach administration inhibited body weight loss and colon shortening, and attenuated the macroscopic and microscopic damage signs, as well as significantly reducing transmural inflammation and boosting the recovery of the mucosal architecture and its muco-secretory function. Additionally, Ach promotes macrophage polarization to the M2 phenotype and was capable of down-regulating significantly the expression of inflammatory proteins COX-2 and iNOS, and at the same time it regulates the antioxidant Nrf-2/HO-1 pathway. In conclusion, this is the first study in which it is demonstrated that the properties of Ach as could be used as a preventive and curative treatment in Crohn’s disease.

scholarly journals Extracellular vesicles package dsDNA to aggravate Crohn’s disease by activating the STING pathway

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Fan Zhao ◽  
Tao Zheng ◽  
Wenbin Gong ◽  
Jie Wu ◽  
Haohao Xie ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Extracellular Vesicles ◽  
Intestinal Inflammation ◽  
Therapeutic Effects ◽  
Murine Colitis ◽  
Sting Pathway ◽  
Deficient Mice

AbstractCrohn’s disease (CD) is an intestinal immune-dysfunctional disease. Extracellular vesicles (EVs) are membrane-enclosed particles full of functional molecules, e.g., nuclear acids. Recently, EVs have been shown to participate in the development of CD by realizing intercellular communication among intestinal cells. However, the role of EVs carrying double-strand DNA (dsDNA) shed from sites of intestinal inflammation in CD has not been investigated. Here we isolated EVs from the plasma or colon lavage of murine colitis and CD patients. The level of exosomal dsDNA, including mtDNA and nDNA, significantly increased in murine colitis and active human CD, and was positively correlated with the disease activity. Moreover, the activation of the STING pathway was verified in CD. EVs from the plasma of active human CD triggered STING activation in macrophages in vitro. EVs from LPS-damaged colon epithelial cells were also shown to raise inflammation in macrophages via activating the STING pathway, but the effect disappeared after the removal of exosomal dsDNA. These findings were further confirmed in STING-deficient mice and macrophages. STING deficiency significantly ameliorated colitis. Besides, potential therapeutic effects of GW4869, an inhibitor of EVs release were assessed. The application of GW4869 successfully ameliorated murine colitis by inhibiting STING activation. In conclusion, exosomal dsDNA was found to promote intestinal inflammation via activating the STING pathway in macrophages and act as a potential mechanistic biomarker and therapeutic target of CD.

scholarly journals The Polymorphism rs17525495 of LTA4H Is Associated with Susceptibility of Crohn’s Disease instead of Intestinal Tuberculosis in a Chinese Han Population

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Zi-qi Yu ◽  
Wen-fei Wang ◽  
Chuan-zhi Zhu ◽  
Ke-hong Zhang ◽  
Xin-chun Chen ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Extrapulmonary Tuberculosis ◽  
Intestinal Tuberculosis ◽  
Taqman Assay ◽  
Jiangxi Province ◽  
Control Group ◽  
Healthy Population ◽  
Therapeutic Effects ◽  
Chinese Han

Background. Because of the similarity of intestinal tuberculosis and Crohn’s disease in disease phenotype, differential diagnosis has always been a clinical problem. Arachidonic acid metabolites play an important role in the inflammatory response of intestinal tuberculosis and Crohn’s disease. Recent studies have shown that the polymorphism locus in the promoter region of LTA4H gene affects LTB4 expression level and the susceptibility to extrapulmonary tuberculosis. Thus, we identified a total of 148 patients with intestinal tuberculosis, 145 with Crohn’s disease, and 700 normal controls in this study. Methods. All the study participants were local Han people from Jiangxi Province in the past eleven years. DNA was extracted from the paraffin-embedded specimens or the whole blood. The LTA4H promoter SNP (rs17525495) was genotyped with TaqMan assay. Results. The T-alleles frequency was not significantly increased in patients with intestinal tuberculosis compared with healthy control group (p=0.630; OR=1.07; 95%CI=0.81-1.41), while patients with Crohn’s disease have significantly increased T allele frequency compared with healthy population (p=0.032; OR=1.34; 95%CI=1.03-1.75). During treatment, the presence of the T allele significantly increased the proportion of Crohn’s patients requiring glucocorticoids (p<0.05). Conclusions. The T allele of LTA4H gene SNP (rs17525495) is a risk factor for Crohn’s disease instead of intestinal tuberculosis. More importantly, there may be a potential association of the different genotypes of rs17525495 with the treatment efficacy of 5-ASA and glucocorticoids in patients with Crohn’s disease. The association between LTA4H polymorphism and drugs therapeutic effects might contribute to the practice of precision medicine and the prediction of clinical outcomes.

Towards an integrated understanding of the therapeutic utility of exclusive enteral nutrition in the treatment of Crohn's disease

2016 ◽  
Vol 7 (4) ◽  
pp. 1741-1751 ◽  
Author(s):  
Páraic Ó Cuív ◽  
Jakob Begun ◽  
Simon Keely ◽  
Peter J. Lewindon ◽  
Mark Morrison
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Enteral Nutrition ◽  
Therapeutic Effects ◽  
Exclusive Enteral Nutrition ◽  
Gut Mucosa ◽  
Therapeutic Utility

The therapeutic effects associated with EEN may be mediated by co-ordinate effects on the host gut mucosa and microbiota.

Therapeutic effect of anti-OX40L and anti-TNF-α MAbs in a murine model of chronic colitis

2003 ◽  
Vol 284 (4) ◽  
pp. G595-G603 ◽  
Author(s):  
T. Totsuka ◽  
T. Kanai ◽  
K. Uraushihara ◽  
R. Iiyama ◽  
M. Yamazaki ◽  
...  
Keyword(s):  
T Cells ◽  
Crohn’S Disease ◽  
T Cell ◽  
Crohn's Disease ◽  
Lamina Propria ◽  
Therapeutic Effect ◽  
Therapeutic Effects ◽  
Chronic Colitis ◽  
Tnf Α ◽  
Ifn Γ

Interaction of OX40 (CD134) on T cells with its ligand (OX40L) on antigen-presenting cells has been implicated in pathogenic T cell activation. This study was performed to explore the involvement of OX40/OX40L in the development of T cell-mediated chronic colitis. We evaluated both the preventive and therapeutic effects of neutralizing anti-OX40L MAb on the development of chronic colitis in SCID mice induced by adoptive transfer of CD4+CD45RBhighT cells as an animal model of Crohn's disease. We also assessed the combination of anti-OX40L and anti-TNF-α MAbs to improve the therapeutic effect. Administration of anti-OX40L MAb markedly ameliorated the clinical and histopathological disease in preventive and therapeutic protocols. In vivo treatment with anti-OX40L MAb decreased CD4+T cell infiltration in the colon and suppressed IFN-γ, IL-2, and TNF-α production by lamina propria CD4+T cells. The combination with anti-TNF-α MAb further improved the therapeutic effect by abolishing IFN-γ, IL-2, and TNF-α production by lamina propria CD4+T cells. Our present results suggested a pivotal role of OX40/OX40L in the pathogenesis of T cell-mediated chronic colitis. The OX40L blockade, especially in combination with the TNF-α blockade, may be a promising strategy for therapeutic intervention of Crohn's disease.

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