scholarly journals Irgm1-deficient mice exhibit Paneth cell abnormalities and increased susceptibility to acute intestinal inflammation

2013 ◽  
Vol 305 (8) ◽  
pp. G573-G584 ◽  
Author(s):  
Bo Liu ◽  
Ajay S. Gulati ◽  
Viviana Cantillana ◽  
Stanley C. Henry ◽  
Elyse A. Schmidt ◽  
...  
Keyword(s):  
Sodium Sulfate ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Paneth Cell ◽  
Dextran Sodium Sulfate ◽  
Inflammatory Disorder ◽  
Immune Mediated ◽  
Clinical Responses ◽  
Granule Morphology ◽  
Intracellular Infections

Crohn's disease (CD) is a chronic, immune-mediated, inflammatory disorder of the intestine that has been linked to numerous susceptibility genes, including the immunity-related GTPase ( IRG) M ( IRGM). IRGs comprise a family of proteins known to confer resistance to intracellular infections through various mechanisms, including regulation of phagosome processing, cell motility, and autophagy. However, despite its association with CD, the role of IRGM and other IRGs in regulating intestinal inflammation is unclear. We investigated the involvement of Irgm1, an ortholog of IRGM, in the genesis of murine intestinal inflammation. After dextran sodium sulfate exposure, Irgm1-deficient [Irgm1 knockout (KO)] mice showed increased acute inflammation in the colon and ileum, with worsened clinical responses. Marked alterations of Paneth cell location and granule morphology were present in Irgm1 KO mice, even without dextran sodium sulfate exposure, and were associated with impaired mitophagy and autophagy in Irgm1 KO intestinal cells (including Paneth cells). This was manifested by frequent tubular and swollen mitochondria and increased LC3-positive autophagic structures. Interestingly, these LC3-positive structures often contained Paneth cell granules. These results suggest that Irgm1 modulates acute inflammatory responses in the mouse intestine, putatively through the regulation of gut autophagic processes, that may be pivotal for proper Paneth cell functioning.

scholarly journals Production of lipid mediators across different disease stages of dextran sodium sulfate-induced colitis in mice

2018 ◽  
Vol 59 (4) ◽  
pp. 586-595 ◽  
Author(s):  
Taiki Hamabata ◽  
Tatsuro Nakamura ◽  
Sakura Masuko ◽  
Shingo Maeda ◽  
Takahisa Murata
Keyword(s):  
Fatty Acid ◽  
Sodium Sulfate ◽  
Acute Inflammation ◽  
Intestinal Inflammation ◽  
Recovery Phase ◽  
Lipid Mediators ◽  
Dextran Sodium Sulfate ◽  
Prostaglandin E ◽  
Induction Phase ◽  
Colon Tissue

Although several studies have revealed the role of different lipid mediators in colitis, the comprehensive analysis of their production across different phases of colitis remained unclear. Here, we performed the following analysis in the dextran sodium sulfate (DSS)-induced colitis model using LC-MS/MS. Oral administration of 2% DSS in mice for 4 days resulted in severe intestinal inflammation by day 7, which gradually subsided by day 18. Based on the disease scoring index (assigned on the basis of fecal condition and weight loss), we defined the phases of colitis as induction (days 0–4), acute inflammation (days 4–7), recovery (days 7–9), and late recovery (days 9–18). Across all phases, 58 lipid mediators were detected in the inflamed colon tissue. In the induction phase, the production of n-6 fatty acid-derived prostaglandin E2 and thromboxane B2 increased by ∼2-fold. In the acute inflammation phase, the production of n-6 fatty acid-derived leukotrienes increased by >10-fold, while that of n-3 fatty acid-derived hydroxyeicosapentaenoic acids and dihydroxyeicosatetraenoic acids decreased. In the recovery phase, a precursor of protectin D1 (17-hydroxydocosahexaenoic acid) increased over 3-fold. These observations suggested dynamic changes in the production of lipid mediators across different phases of the disease and their potential regulation in healing colitis.

Malt1 blocks IL-1β production by macrophages in vitro and limits dextran sodium sulfate-induced intestinal inflammation in vivo

2018 ◽  
Vol 104 (3) ◽  
pp. 557-572 ◽  
Author(s):  
Mahdis Monajemi ◽  
Yvonne C. F. Pang ◽  
Saelin Bjornson ◽  
Susan C. Menzies ◽  
Nico van Rooijen ◽  
...  
Keyword(s):  
Sodium Sulfate ◽  
Intestinal Inflammation ◽  
Dextran Sodium Sulfate

Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice

2009 ◽  
Vol 296 (3) ◽  
pp. G685-G695 ◽  
Author(s):  
Stephan C. Bischoff ◽  
Reiner Mailer ◽  
Oliver Pabst ◽  
Gisela Weier ◽  
Wanda Sedlik ◽  
...  
Keyword(s):  
Serotonin Reuptake ◽  
Sulfonic Acid ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Colonic Motility ◽  
Trinitrobenzene Sulfonic Acid ◽  
Targeted Deletion ◽  
Immune Mediated ◽  
Serotonin Reuptake Transporter

Serotonin (5-HT) regulates peristaltic and secretory reflexes in the gut. The serotonin reuptake transporter (SERT; SLC6A4), which inactivates 5-HT, is expressed in the intestinal mucosa and the enteric nervous system. Stool water content is increased and colonic motility is irregular in mice with a targeted deletion of SERT. We tested the hypotheses that 5-HT plays a role in regulating intestinal inflammation and that the potentiation of serotonergic signaling that results from SERT deletion is proinflammatory. Rectal installation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to induce an immune-mediated colitis, which was compared in SERT knockout mice and littermate controls. Intestinal myeloperoxidase and histamine levels were significantly increased, whereas the survival rate and state of health were significantly decreased in TNBS-treated mice that lacked SERT. Deletion of SERT thus increases the severity of TNBS colitis. These data suggest that 5-HT and its SERT-mediated termination play roles in intestinal immune/inflammatory responses in mice.

MyD88-deficient mice develop severe intestinal inflammation in dextran sodium sulfate colitis

2005 ◽  
Vol 40 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Akihiro Araki ◽  
Takanori Kanai ◽  
Takahiro Ishikura ◽  
Shin Makita ◽  
Koji Uraushihara ◽  
...  
Keyword(s):  
Sodium Sulfate ◽  
Intestinal Inflammation ◽  
Dextran Sodium Sulfate ◽  
Deficient Mice

scholarly journals Interleukin-10 is Differentially Expressed in the Small Intestine and the Colon Experiencing Chronic Inflammation and Ulcerative Colitis Induced by Dextran Sodium Sulfate in Young Pigs

2017 ◽  
pp. 147-162 ◽  
Author(s):  
D. LACKEYRAM ◽  
D. YOUNG ◽  
C. J. KIM ◽  
C. YANG ◽  
T. L. ARCHBOLD ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Chronic Inflammation ◽  
Chronic Ulcerative Colitis ◽  
Sodium Sulfate ◽  
Intestinal Inflammation ◽  
Interleukin 10 ◽  
Dextran Sodium Sulfate ◽  
Mrna Abundance ◽  
Control Group ◽  
Young Pigs

Intestinal inflammation induced with dextran sodium sulfate (DSS) is used to study acute or chronic ulcerative colitis in animal models. Decreased gut tissue anti-inflammatory cytokine IL-10 concentration and mRNA abundance are associated with the development of chronic bowel inflammation. Twelve piglets of 3 days old were fitted with an intragastric catheter and randomly allocated into control and DSS groups by administrating either sterile saline or 1.25 g of DSS/kg body weight (BW) in saline per day, respectively, for 10 days. Growth rate and food conversion efficiency were reduced (p<0.05) in the DSS piglets compared with the control group. Quantitative histopathological grading of inflammation in the jejunum and colon collectively showed that the DSS treatment resulted in 12 fold greater (p<0.05) inflammation severity scoring in the colon than in the jejunum, indicative of chronic ulcerative colitis in the colon. Upper gut permeability endpoint was 27.4 fold higher (p<0.05) in the DSS group compared with the control group. The DSS group had higher concentrations and mRNA abundances (p<0.05) of TNF- and IL-6 in the jejunal and colonic tissues compared with the control group. Colonic concentration and mRNA abundance of IL-10 were reduced (p<0.05), however, jejunal IL-10 mRNA abundance was increased (p<0.05) in the DSS group compared with the control group. In conclusion, administration of DSS at 1.25 g/kg BW for 10 days respectively induced acute inflammation in the jejunum and chronic inflammation and ulcerative colitis in the colon with substantially decreased colonic concentration and mRNA abundance of IL-10 in the young pigs, mimicking the IL-10 expression pattern in humans associated with chronic bowel inflammation.

scholarly journals Lactobacillus bulgaricus inhibits colitis-associated cancer via a negative regulation of intestinal inflammation in azoxymethane/dextran sodium sulfate model

2020 ◽  
Vol 26 (43) ◽  
pp. 6782-6794
Author(s):  
Denise Sayuri Calheiros Silveira ◽  
Luciana Chain Veronez ◽  
Luís Carlos Lopes-Júnior ◽  
Elen Anatriello ◽  
Mariângela Ottoboni Brunaldi ◽  
...  
Keyword(s):  
Sodium Sulfate ◽  
Intestinal Inflammation ◽  
Negative Regulation ◽  
Dextran Sodium Sulfate ◽  
Lactobacillus Bulgaricus

scholarly journals The Adenosine System at the Crossroads of Intestinal Inflammation and Neoplasia

2020 ◽  
Vol 21 (14) ◽  
pp. 5089
Author(s):  
Vanessa D’Antongiovanni ◽  
Matteo Fornai ◽  
Carolina Pellegrini ◽  
Laura Benvenuti ◽  
Corrado Blandizzi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Receptor Subtype ◽  
Colorectal Tumorigenesis ◽  
Adverse Conditions ◽  
Immune Mediated ◽  
A1 Receptor ◽  
G Protein Coupled ◽  
Critical Overview

Adenosine is a purine nucleoside, resulting from the degradation of adenosine triphosphate (ATP). Under adverse conditions, including hypoxia, ischemia, inflammation, or cancer, the extracellular levels of adenosine increase significantly. Once released, adenosine activates cellular signaling pathways through the engagement of the four known G-protein-coupled receptors, adenosine A1 receptor subtype (A1), A2A, A2B, and A3. These receptors, expressed virtually on all immune cells, mitigate all aspects of immune/inflammatory responses. These immunosuppressive effects contribute to blunt the exuberant inflammatory responses, shielding cells, and tissues from an excessive immune response and immune-mediated damage. However, a prolonged persistence of increased adenosine concentrations can be deleterious, participating in the creation of an immunosuppressed niche, ideal for neoplasia onset and development. Based on this evidence, the present review has been conceived to provide a comprehensive and critical overview of the involvement of adenosine system in shaping the molecular mechanisms underlying the enteric chronic inflammation and in promoting the generation of an immunosuppressive niche useful for the colorectal tumorigenesis.

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