scholarly journals P2Y12 receptor as a new target for electroacupuncture relieving comorbidity of visceral pain and depression of inflammatory bowel disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yanzhen Li ◽  
Hong Zhang ◽  
Jingwen Yang ◽  
Muouyang Zhan ◽  
Xuefei Hu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Visceral Pain ◽  
Preference Test ◽  
Tail Suspension Test ◽  
P2y12 Receptor ◽  
Trinitrobenzene Sulfonic Acid ◽  
P2y12 Inhibitors ◽  
Inflammatory Bowel ◽  
Sucrose Preference Test

Abstract Background The P2Y12 receptor is a kind of purinoceptor that is engaged in platelet aggregation, and P2Y12 inhibitors have been used in clinical antithrombotic therapy. The P2Y12 receptor in microglia induces interleukin-1β (IL-1β) expression, which is a key mediator of depression in the brain. Although peripheral P2Y12 is involved in neuropathic pain, whether P2Y12 expression in the medial prefrontal cortex (mPFC) is associated with comorbidities of visceral pain and depression remains unclear. Accumulating evidence suggests that electroacupuncture (EA) is effective in treating inflammatory bowel disease (IBD), but its mechanism is unknown. This study aimed to determine whether P2Y12 expression in the mPFC is associated with comorbidities of visceral pain and depression in IBD and whether EA treats IBD by targeting the P2Y12 receptor. Methods We used 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced IBD mice. P2Y12 short hairpin RNA (shRNA) was stereotaxically injected into the bilateral mPFC. EA was performed on bilateral “Dachangshu” (BL25) acupoints once a day for 7 days. Von Frey filaments and colorectal distension were used to detect the mechanical pain threshold and visceral pain sensitivity. The sucrose preference test, tail suspension test and forced swimming test were used to evaluate depression in mice. Western blotting was used to test the expression of P2Y12 and IL-1β. Immunofluorescence staining was used to assess microglial activity. Results We found that IBD mice presented visceral pain and depression associated with increased P2Y12 expression in the mPFC. P2Y12 shRNA significantly attenuated visceral pain and depression in IBD mice. P2Y12 shRNA significantly downregulated IL-1β expression and inhibited the activation of microglia in the mPFC of IBD mice. Meanwhile, EA played a similar role of P2Y12 shRNA. EA significantly downregulated P2Y12 expression, weakened the activation of microglia, and then inhibited IL-1β expression in the mPFC, thus relieving visceral pain and depression in IBD mice. Conclusion The present study provided new ideas that the P2Y12 receptor in the mPFC could be a new target for the treatment of comorbid visceral pain and depression by EA. This may not only deepen our understanding of the analgesic and antidepressant mechanisms of EA but also promote the application of EA to treat IBD.

scholarly journals An objective in vivo diagnostic method for inflammatory bowel disease

2018 ◽  
Vol 5 (3) ◽  
pp. 180107 ◽  
Author(s):  
Sophie C. Payne ◽  
Robert K. Shepherd ◽  
Alicia Sedo ◽  
James B. Fallon ◽  
John B. Furness
Keyword(s):  
Inflammatory Bowel Disease ◽  
Real Time ◽  
Bowel Disease ◽  
Experimental Models ◽  
Mucosal Barrier ◽  
Trinitrobenzene Sulfonic Acid ◽  
Inflammatory Damage ◽  
Mucosal Barrier Function ◽  
Inflammatory Bowel

Inflammatory damage to the bowel, as occurs in inflammatory bowel disease (IBD), is debilitating to patients. In both patients and animal experimental models, histological analyses of biopsies and endoscopic examinations are used to evaluate the disease state. However, such measurements often have delays and are invasive, while endoscopy is not quantitatively objective. Therefore, a real-time quantitative method to assess compromised mucosal barrier function is advantageous. We investigated the correlation of in vivo changes in electrical transmural impedance with histological measures of inflammation. Four platinum (Pt) ball electrodes were placed in the lumen of the rat small intestine, with a return electrode under the skin. Electrodes placed within the non-inflamed intestine generated stable impedances during the 3 h testing period. Following an intraluminal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), an established animal model of IBD, impedances in the inflamed region significantly decreased relative to a region not exposed to TNBS ( p  < 0.05). Changes in intestinal transmural impedance were correlated ( p  < 0.05) with histologically assessed damage to the mucosa and increases in neutrophil, eosinophil and T-cell populations at 3 h compared with tissue from control regions. This quantitative, real-time assay may have application in the diagnosis and clinical management of IBD.

scholarly journals Mouse model of ulcerative colitis using trinitrobenzene sulfonic acid

2015 ◽  
Vol 10 (4) ◽  
pp. 860
Author(s):  
Irfan Ahmad Rather ◽  
Vivek K. Bajpai ◽  
Nam Gyeong-Jun
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Mouse Model ◽  
Bowel Disease ◽  
Sulfonic Acid ◽  
Intestinal Inflammation ◽  
Cost Effective ◽  
Trinitrobenzene Sulfonic Acid ◽  
Clinical Presentations ◽  
Inflammatory Bowel

<p>Animal model of intestinal inflammation is of paramount significance that aids in discerning the pathologies underlying ulcerative colitis and Crohn’s disease, the two clinical presentations of inflammatory bowel disease. The 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis model represents one such intestinal inflammation-prototype that is generated in susceptible strains of mice through intra-rectal instillation of compound TNBS. In this paper, we demonstrate the experimental induction of TNBS-mediated colitis in a susceptible strain of ICR mice. This can be done by the following steps: a) acclimation, b) induction and c) observation. TNBS-mouse model provides the information in shortest possible time and simultaneously represents a cost effective and highly reproducible model method of studying the pathogenesis of inflammatory bowel disease.</p><p><strong>Video Clips</strong></p><p><a href="https://youtube.com/v/6MsuIGzH3uA">Acclimation and induction of TNBS</a>:          4.5 min</p><p><a href="https://youtube.com/v/ya66SNwoVag">Observation and drug administration</a>:      1.5 min</p>

A moderately elevated soy protein diet mitigates inflammatory changes in gut and in bone turnover during chronic TNBS-induced inflammatory bowel disease

2019 ◽  
Vol 44 (6) ◽  
pp. 595-605 ◽  
Author(s):  
Corinne E. Metzger ◽  
S. Anand Narayanan ◽  
David C. Zawieja ◽  
Susan A. Bloomfield
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bone Turnover ◽  
Soy Protein ◽  
Bowel Disease ◽  
Protein Diet ◽  
Trinitrobenzene Sulfonic Acid ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
The Impact ◽  
Colitis Model

Inflammatory bowel disease is a condition that leads to gut pathologies such as abnormal lymphatic architecture, as well as to systemic comorbidities such as bone loss. Furthermore, current therapies are limited to low efficacy and incur side effects. Dietary interventions have been explored minimally, but may provide a treatment for improving gut outcomes and comorbidities. Indeed, plant-based soy protein has been shown to exert anti-inflammatory effects. Here, we tested the impact of a moderately elevated soy protein diet in a chronic, 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model on gut and bone inflammatory-mediated pathophysiological adaptations. Colitis was induced by intrarectal administration of TNBS. Gut histopathology was scored, and lymphatic structural changes and the local inflammatory state were assessed via immunofluorescence. In addition, the effects of gut inflammation on bone turnover and osteocyte proteins were determined via histomorphometry and immunohistochemistry, respectively. The moderately elevated soy protein diet produced improvements in both colonic and bone tissues. In TNBS animals given the soy protein intervention, colon histological scores were reduced and the abnormal lymphatic architecture resolved. There were also improvements in bone formation and reduced bone resorption. In addition, TNBS increased inflammatory cytokines such as tumor necrosis factor-α and receptor activator of nuclear factor κ-B ligand in the gut and bone, but this was resolved in both tissues with the dietary soy protein intervention. The moderately elevated soy protein diet mitigated gut and bone inflammation in a chronic, TNBS-induced colitis model, demonstrating the potential for soy protein as a potential anti-inflammatory dietary intervention for inflammatory bowel disease.

scholarly journals Inflammatory bowel disease-associated ubiquitin ligase RNF183 promotes lysosomal degradation of DR5 and TRAIL-induced caspase activation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yan Wu ◽  
Yuka Kimura ◽  
Takumi Okamoto ◽  
Koji Matsuhisa ◽  
Rie Asada ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Ubiquitin Ligase ◽  
Bowel Disease ◽  
Early Stage ◽  
Caspase 8 ◽  
Trinitrobenzene Sulfonic Acid ◽  
Death Receptor 5 ◽  
Caspase Activation ◽  
Lysosomal Degradation ◽  
Inflammatory Bowel

AbstractRNF183 is a ubiquitin ligase containing RING-finger and transmembrane domains, and its expression levels are increased in patients with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, and in 2,4,6-trinitrobenzene sulfonic acid-induced colitis mice. Here, we further demonstrate that RNF183 was induced to a greater degree in the dextran sulfate sodium (DSS)-treated IBD model at a very early stage than were inflammatory cytokines. In addition, fluorescence-activated cell sorting and polymerase chain reaction analysis revealed that RNF183 was specifically expressed in epithelial cells of DSS-treated mice, which suggested that increased levels of RNF183 do not result from the accumulation of immune cells. Furthermore, we identified death receptor 5 (DR5), a member of tumour necrosis factor (TNF)-receptor superfamily, as a substrate of RNF183. RNF183 mediated K63-linked ubiquitination and lysosomal degradation of DR5. DR5 promotes TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis signal through interaction with caspase-8. Inhibition of RNF183 expression was found to suppress TRAIL-induced activation of caspase-8 and caspase-3. Thus, RNF183 promoted not only DR5 transport to lysosomes but also TRAIL-induced caspase activation and apoptosis. Together, our results provide new insights into potential roles of RNF183 in DR5-mediated caspase activation in IBD pathogenesis.

scholarly journals Involvement of Brn3a-positive spinal dorsal horn neurons in the transmission of visceral pain in inflammatory bowel disease model mice

2021 ◽  
Author(s):  
Kazuhiko Nishida ◽  
Shinji Matsumura ◽  
Takuya Kobayashi
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dorsal Horn ◽  
Bowel Disease ◽  
Spinal Dorsal Horn ◽  
Visceral Pain ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Pain Transmission ◽  
Inflammatory Bowel ◽  
Spinal Dorsal Horn Neurons

Spinal dorsal horn plays crucial roles in the transmission and processing of somatosensory information. Although spinal neural circuits which process several distinct types of cutaneous sensation have been extensively studied, those responsible for visceral pain transmission remain poorly understood. In the present study, we analyzed the dextran sodium sulfate (DSS)-induced inflammatory bowel disease (IBD) model mice to characterize the spinal dorsal horn neurons involved in visceral pain transmission. DSS-treated mice exhibited increased abdominal licking behavior, suggestive of experiencing visceral pain. Immunostaining of c-fos, a marker indicating neuronal activity, demonstrated that numerous c-fos-positive cells were found bilaterally in the lumbosacral spinal dorsal horn, and their distribution was particularly abundant in the shallow dorsal horn. Neurochemical characterization of these neurons revealed that the percentage of the POU transcription factor Brn3a-positive neurons among the c-fos-positive neurons in the shallow dorsal horn was 30-40% in DSS-treated mice, which was significantly higher than that in the somatic pain model mice. We further demonstrated by neuronal tracing that within the shallow dorsal horn, Brn3a-positive neurons are represented more highly in spino-solitary projection neurons than in spino-parabrachial projection ones. These results raised the possibility that Brn3a-positive spinal dorsal horn neurons make a large contribution to visceral pain transmission, and part of which was mediated through spino-solitary pathway.

scholarly journals In Vitro and in Vivo Evaluation of Pectin-based Melatonin Nanoparticles for the Treatment of Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Serkan Yener ◽  
Kazime Gonca Akbulut ◽  
Resul Karakuş ◽  
Deniz Erdoğan ◽  
Füsun Acartürk
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Histological Evaluation ◽  
Trinitrobenzene Sulfonic Acid ◽  
Colonic Tissue ◽  
In Vivo Evaluation ◽  
Promising Alternative ◽  
Inflammatory Bowel

Abstract Inflammatory bowel disease (IBD) is a general term including long-term inflammatory disorders of all or some parts of the digestive system. Nanoparticles (NPs) can accumulate in the inflamed zone independently of the polymers’ mucoadhesive character. The aim of this study was to prepare and investigate the melatonin loaded pectin-based nanoparticles for Inflammatory Bowel Disease (IBD). Melatonin (MEL) was loaded into nanoparticle system with a modified ionotropic-gelation method. In vitro characterization studies of the nanoparticles were carried out. The effectiveness of the oral and intracolonically administered nanoparticles were investigated in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rats. The indicators of oxidative stress in the colonic tissue like nitric oxide, malondialdehyde, glutathione, tumor necrosis factor-alpha, Interleukin (IL)-10, and IL-17 levels were investigated. In addition, the histological evaluation was performed. The mean diameter, zeta potential and polydispersity index values of the obtained nanoparticles were 75.3±3.3 nm, 24.24±1.03 mV and 0.109±0.067, respectively. The in vitro drug release studies showed that 84.0±0.7% of the drug was released from the nanoparticles for 8 h. MEL-loaded pectin nanoparticles ameliorated the TNBS-induced colitis. Treatment of the melatonin decreased the damage score by 73.2% in oral and by 67.1% in intracolonic route, respectively. A meaningful decrease was observed in colonic fibrosis, oxidative stress, and inflammatory parameters of the colon accompanying histologic injury. The results of the experiments and histological data showed that MEL-loaded calcium pectinate nanoparticle may be a promising alternative in colonic tissue damage which develops due to oxidative stress in IBD.

scholarly journals Daikenchuto attenuates visceral pain and suppresses eosinophil infiltration in inflammatory bowel disease in murine models

JGH Open ◽  
2020 ◽  
Vol 4 (6) ◽  
pp. 1146-1154
Author(s):  
Yoko Kogure ◽  
Hirosato Kanda ◽  
Shenglan Wang ◽  
Yongbiao Hao ◽  
Junxiang Li ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Visceral Pain ◽  
Eosinophil Infiltration ◽  
Murine Models ◽  
Inflammatory Bowel

Granulocytes Infiltrate The Intestine In a Zebrafish Model Of Inflammatory Bowel Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2276-2276
Author(s):  
Brenda Geiger ◽  
Aileen W. Zhen ◽  
Efi Kokkotou ◽  
Paula G. Fraenkel
Keyword(s):  
Inflammatory Bowel Disease ◽  
Intestinal Mucosa ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Conflicts Of Interest ◽  
Post Treatment ◽  
Trinitrobenzene Sulfonic Acid ◽  
Zebrafish Model ◽  
Transcript Levels ◽  
Inflammatory Bowel

Abstract Inflammatory bowel disease (IBD) is a condition in which lymphocytes and neutrophils infiltrate the intestine, stimulate the production of various inflammatory cytokines, and injure the intestinal mucosa. Because of the conserved aspects of hematopoiesis in the zebrafish, we hypothesized that a zebrafish model of IBD would reproduce human features of the disease, while retaining desirable aspects of zebrafish disease models including small size, low cost, and ease of chemical and genetic screening. We used adult transgenic zebrafish expressing eGFP under control of a myeloperoxidase promoter (Tg(mpx:eGFP) to trace the activity of granulocytes following intrarectal injection with trinitrobenzene sulfonic acid (TNBS), 1.6 mmole/gram body weight, or an equivalent volume of vehicle alone (30% ethanol). The zebrafish were sacrificed 6 hours’ post-treatment for assessment of changes in intestinal architecture, intestinal infiltration by myeloperoxidase-positive leukocytes, and cytokine transcript levels using histology, flow cytometry, and quantitative realtime RT-PCR, respectively. At 6 hours post-treatment, we detected a mononuclear infiltrate in the intestinal mucosa and a 10-fold increase in the number of myeloperoxidase-positive leukocytes in the intestines of TNBS-treated fish vs controls (0.614%±0.202% vs. 0.052%±0.014%, p=0.0269; n=6-7 fish per group). We also observed a significant increase in the transcript levels of interleukin-1beta (6,935±2,454 AU vs 100±28 AU, p=0.0179), interleukin-8 (246 ± 63 AU vs 100 ± 21 AU, p=0.05) and interleukin-10 (385 ± 84 AU vs 100± 8 AU p=0.0055) in the intestines of fish injected with TNBS vs vehicle alone (n=9-10 fish per group). These findings resemble those seen in patients and mammalian chemical injury models of IBD. They will provide the basis for further study of the mechanisms controlling intestinal inflammation in IBD. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document