scholarly journals Review Article. Absent in melanoma 2 (AIM2) in the intestine: diverging actions with converging consequences

Inflammasome ◽  
2017 ◽  
Vol 3 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Wiebe Vanhove ◽  
Paul M. Peeters ◽  
Isabelle Cleynen ◽  
Gert Van Assche ◽  
Marc Ferrante ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Intestinal Epithelial ◽  
Intestinal Immunity ◽  
Intestinal Homeostasis ◽  
Caspase 1 ◽  
Essential Components ◽  
Food Antigens ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Molecular Patterns

AbstractThe intestinal mucosa is a difficult environment to maintain homeostasis as it is constantly challenged by microbial and food antigens. Maintaining an intact epithelial barrier, a continuous turnover of intestinal epithelial cells and normobiosis of the gut microbiota are essential components to prevent intestinal diseases such as inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Inflammasomes are critical immune regulators that are involved in all of these processes. They are multiprotein complexes able to assemble upon interaction with a noxious stimulus that will subsequently lead to caspase-1 activation. Activated caspase-1 will orchestrate the maturation and release of proinflammatory cytokines IL-1β and IL-18, and induce pyroptosis, an inflammatory form of cell death. Both cytokine release and pyroptosis are initiated after detection of molecular patterns by a distinct inflammasome sensor protein. Absent in melanoma 2 (AIM2) is such an inflammasome sensor that specifically responds to the presence of double stranded DNA (dsDNA) in the cytoplasm, leading to the recruitment and activation of caspase-1. Recent studies revealed additional roles of AIM2 in controlling epithelial cell proliferation, tight junction expression and the microbiome. Therefore, AIM2 plays a significant role in maintaining intestinal homeostasis. This review focuses on the multifunctional role of AIM2 in intestinal homeostasis by regulating intestinal immunity and preventing colorectal cancer development.

scholarly journals Toll-like receptors 2 and 4 modulate intestinal IL-10 differently in ileum and colon

2017 ◽  
Vol 6 (3) ◽  
pp. 446-453 ◽  
Author(s):  
Eva Latorre ◽  
Elena Layunta ◽  
Laura Grasa ◽  
Julián Pardo ◽  
Santiago García ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Cell Model ◽  
Immune Recognition ◽  
Intestinal Epithelial ◽  
Intestinal Homeostasis ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Gram Negative Organisms ◽  
Tlr4 Activation

Background Inflammatory bowel diseases are consequence of an intestinal homeostasis breakdown in which innate immune dysregulation is implicated. Toll-like receptor (TLR)2 and TLR4 are immune recognition receptors expressed in the intestinal epithelium, the first physical-physiological barrier for microorganisms, to inform the host of the presence of Gram-positive and Gram-negative organisms. Interleukin (IL)-10 is an essential anti-inflammatory cytokine that contributes to maintenance of intestinal homeostasis. Aim Our main aim was to investigate intestinal IL-10 synthesis and release, and whether TLR2 and TLR4 are determinants of IL-10 expression in the intestinal tract. Methods We used Caco-2 cell line as an enterocyte-like cell model, and also ileum and colon from mice deficient in TLR2, TLR4 or TLR2/4 to test the involvement of TLR signaling. Results Intestinal epithelial cells are able to synthesize and release IL-10 and their expression is increased after TLR2 or TLR4 activation. IL-10 regulation seems to be tissue specific, with IL-10 expression in the ileum regulated by a compensation between TLR2 and TLR4 expression, whereas in the colon, TLR2 and TLR4 affect IL-10 expression independently. Conclusions Intestinal epithelial cells could release IL-10 in response to TLR activation, playing an intestinal tissue-dependent and critical intestinal immune role.

scholarly journals Are Volatile Organic Compounds Accurate Markers in the Assessment of Colorectal Cancer and Inflammatory Bowel Diseases? A Review

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2361
Author(s):  
Filippo Vernia ◽  
Marco Valvano ◽  
Stefano Fabiani ◽  
Gianpiero Stefanelli ◽  
Salvatore Longo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Volatile Organic Compounds ◽  
Organic Compounds ◽  
Inflammatory Bowel Diseases ◽  
Screening Programs ◽  
Inflammatory Status ◽  
Incidence And Mortality ◽  
Volatile Organic ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the Western world. Early detection decreases incidence and mortality. Screening programs based on fecal occult blood testing help identify patients requiring endoscopic examination, but accuracy is far from optimal. Among the alternative strategies, volatile organic compounds (VOCs) represent novel potentially useful biomarkers of colorectal cancer. They also represent a promising tool for the screening of both intestinal inflammation and related CRC. The review is focused on the diagnostic potential of VOCs in sporadic CRC and in inflammatory bowel diseases (IBD), which increase the risk of CRC, analyzing future clinical applications. Despite limitations related to inadequate strength of evidence, differing analytical platforms identify different VOCs, and this unconventional approach for diagnosing colorectal cancer is promising. Some VOC profiles, besides identifying inflammation, seem disease-specific in inflammatory bowel diseases. Thus, breath, urine, and fecal VOCs provide a new and promising clinical approach to differential diagnosis, evaluation of the inflammatory status, and possibly the assessment of treatment efficacy in IBD. Conversely, specific VOC patterns correlating inflammatory bowel disease and cancer risk are still lacking, and studies focused on this issue are strongly encouraged. No prospective studies have assessed the risk of CRC development by using VOCs in samples collected before the onset of disease, both in the general population and in patients with IBD.

Tu1198 Intestinal Epithelial Cell Extrusion and Microbial Virulence Are Altered in Pediatric Inflammatory Bowel Diseases

2014 ◽  
Vol 146 (5) ◽  
pp. S-781
Author(s):  
Deenaz Zaidi ◽  
Michael Bording-Jorgenson ◽  
Hien Q. Huynh ◽  
Yuefei Lou ◽  
Julia J. Liu ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Epithelial Cell ◽  
Intestinal Epithelial ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Cell Extrusion

scholarly journals Procoagulatory State in Inflammatory Bowel Diseases Is Promoted by Impaired Intestinal Barrier Function

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Luca Pastorelli ◽  
Elena Dozio ◽  
Laura Francesca Pisani ◽  
Massimo Boscolo-Anzoletti ◽  
Elena Vianello ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Intestinal Barrier ◽  
Systemic Circulation ◽  
Intestinal Barrier Function ◽  
Inflammatory Conditions ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Molecular Patterns ◽  
D Dimer

Inflammatory and immune mediated disorders are risk factors for arterial and venous thromboembolism. Inflammatory bowel diseases (IBD) confer an even greater risk of thromboembolic events than other inflammatory conditions. It has been shown that IBD patients display defective intestinal barrier functions. Thus, pathogen-associated molecular patterns (PAMPs) coming from the intestinal bacterial burden might reach systemic circulation and activate innate immunity receptors on endothelial cells and platelets, promoting a procoagulative state. Aim of the study was to test this hypothesis, correlating the presence of circulating PAMPs with the activation of innate immune system and the activation of the coagulatory cascade in IBD patients. Specifically, we studied lipopolysaccharide (LPS), Toll-like receptor (TLR) 2, TLR4, and markers of activated coagulation (i.e., D-Dimer and prothrombin fragmentF1+2) in the serum and plasma of IBD patients. We found that LPS levels are increased in IBD and correlate with TLR4 concentrations; although a mild correlation between LPS and CRP levels was detected, clinical disease activity does not appear to influence circulating LPS. Instead, serum LPS correlates with both D-Dimer andF1+2measurements. Taken together, our data support the role of an impairment of intestinal barrier in triggering the activation of the coagulatory cascade in IBD.

Proteomic response of inflammatory stimulated intestinal epithelial cells to in vitro digested plums and cabbages rich in carotenoids and polyphenols

2016 ◽  
Vol 7 (10) ◽  
pp. 4388-4399 ◽  
Author(s):  
Anouk Kaulmann ◽  
Sébastien Planchon ◽  
Jenny Renaut ◽  
Yves-Jacques Schneider ◽  
Lucien Hoffmann ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Epithelial Cells ◽  
Intestinal Cells ◽  
Intestinal Epithelial ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Proteomic Response

Proteomic response of intestinal cells as a model of inflammatory bowel diseases to digested plum and cabbage rich in polyphenols and carotenoids.

scholarly journals Plumericin Protects against Experimental Inflammatory Bowel Disease by Restoring Intestinal Barrier Function and Reducing Apoptosis

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 67 ◽  
Author(s):  
Shara Francesca Rapa ◽  
Rosanna Di Paola ◽  
Marika Cordaro ◽  
Rosalba Siracusa ◽  
Ramona D’Amico ◽  
...  
Keyword(s):  
Barrier Function ◽  
Structural Integrity ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Intestinal epithelial barrier impairment plays a key pathogenic role in inflammatory bowel diseases (IBDs). In particular, together with oxidative stress, intestinal epithelial barrier alteration is considered as upstream event in ulcerative colitis (UC). In order to identify new products of natural origin with a potential activity for UC treatment, this study evaluated the effects of plumericin, a spirolactone iridoid, present as one of the main bioactive components in the bark of Himatanthus sucuuba (Woodson). Plumericin was evaluated for its ability to improve barrier function and to reduce apoptotic parameters during inflammation, both in intestinal epithelial cells (IEC-6), and in an animal experimental model of 2, 4, 6-dinitrobenzene sulfonic acid (DNBS)-induced colitis. Our results indicated that plumericin increased the expression of adhesion molecules, enhanced IEC-6 cells actin cytoskeleton rearrangement, and promoted their motility. Moreover, plumericin reduced apoptotic parameters in IEC-6. These results were confirmed in vivo. Plumericin reduced the activity of myeloperoxidase, inhibited the expression of ICAM-1, P-selectin, and the formation of PAR, and reduced apoptosis parameters in mice colitis induced by DNBS. These results support a pharmacological potential of plumericin in the treatment of UC, due to its ability to improve the structural integrity of the intestinal epithelium and its barrier function.

Risk of colorectal cancer in inflammatory bowel diseases

2020 ◽  
Vol 64 ◽  
pp. 51-60 ◽  
Author(s):  
Muhammad Shahid Nadeem ◽  
Vikas Kumar ◽  
Fahad A. Al-Abbasi ◽  
Mohammad Amjad Kamal ◽  
Firoz Anwar
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Diseases ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Faecal Biomarkers in Inflammatory Bowel Diseases: Calprotectin Versus Lipocalin-2—a Comparative Study

2020 ◽  
Author(s):  
Andreas Zollner ◽  
Andreas Schmiderer ◽  
Simon J Reider ◽  
Georg Oberhuber ◽  
Alexandra Pfister ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Bowel Diseases ◽  
Low Grade ◽  
Intestinal Epithelial ◽  
Lipocalin 2 ◽  
Monitoring Tools ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Histological Remission

Abstract Background and Aims Faecal biomarkers, particularly calprotectin [FCAL], have become important diagnostic and monitoring tools in inflammatory bowel diseases [IBD]. As FCAL is mainly produced by neutrophils, we hypothesised that faecal lipocalin-2 [FLCN2], also expressed by intestinal epithelial cells [IEC], could be beneficial in specific clinical situations. Methods We compared clinical and endoscopic activity-related correlations between FCAL and FLCN2, assayed from the same sample, in a cohort of 132 patients (72 Crohn’s disease [CD]) and 40 controls. A detailed analysis of cellular origins was done by confocal microscopy and flow cytometry. To evaluate the potential to detect low-grade inflammation, we studied faecal and tissue concentrations in a cohort with clinical, endoscopic, and histological remission. Results There was an excellent correlation between FCAL and FLCN2 [rS = 0.87, p <0.001] and comparable sensitivity and specificity to predict clinical and endoscopic disease activity, with optimal thresholds for endoscopic activity of 73.4 and 1.98 µg/g in ulcerative colitis [UC] and 78.4 and 0.56 µg/g in Crohn’s disease for FCAL and FLCN2, respectively. Strong co-expression of both proteins was observed in granulocytes and macrophages. IECs expressed LCN2 but not CAL. In our IBD cohort in deep remission neither FCAL nor FLCN2 was different from controls; yet mucosal LCN2 but not CAL expressions remained elevated in the rectum of UC and the ileum of CD patients. Conclusions This study corroborates the diagnostic equivalence of FLCN2 and FCAL in IBD. In remission, persistent mucosal overexpression renders LCN2 an attractive candidate for molecular inflammation warranting further investigation.

Sign in / Sign up

Export Citation Format

Share Document