NOD-Like Receptors in Intestinal Homeostasis and  Epithelial Tissue Repair

Parlato, Marianna; Yeretssian, Garabet

doi:10.3390/ijms15069594

Cited by 65 publications

(40 citation statements)

References 291 publications

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“…However, MUC2 is also significantly upregulated for C3H Conv C1200 and 129 ASF C600 groups. Thus, upregulated signaling of MUC2 could be due to goblet cells in organoids somehow sensing the disruption, and are preparing for reparation and protection of the epithelial cells (Parlato & Yeretssian, ). From Parlato and Yeretssian () a signal transduction pathway involving MUC2 and NF‐kB for intestinal epithelial tissue repair has been mentioned.…”

Section: Discussionmentioning

confidence: 99%

Vitamin C and B₃ as new biomaterials to alter intestinal stem cells

Lohman

Bratlie

et al. 2019

J Biomedical Materials Res

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Vitamin C (ascorbic acid) and vitamin B3 (niacin) have been extensively studied since the 20th century. In the area of stem cell biology, vitamin C has shown its direct impact toward homeostasis and epigenetic changes (D'Aniello et al., Stem Cells International, 2017, 1–16). Vitamin B3 aids in maintaining healthy intestinal homeostasis and reducing gut inflammation by participating in the rapamycin signaling pathway (Kumar et al., The American Journal of Physiology‐Gastrointestinal and Liver Physiology, 2013). In this study, vitamin C and vitamin B3 (600 and 1,200 μg/mL) have been explored as potential new biomaterials to study their effects on four types of intestinal stem cells which are isolated from mice bearing different microbiota. We observed that C3H ASF and 129 ASF IL‐10 are more sensitive towardB7 600 μg/mL vitamin B3 and 1,200 μg/mL vitamin C. The lowest growth rate and viability for all types of organoids was with 1,200 μg/mL vitamin C. From quantitative polymerase chain reaction analysis (qPCR analysis), MUC2 was upregulated for 129 ASF and C3H Conv when exposed to 600 μg/mL and 1,200 μg/mL vitamin C. It suggests that large amounts of glycoprotein may be produced after adding high concentrations of vitamin C. Since inflammatory bowel disease has low level of MUC2, this finding may be helpful in restoring mucosal health by upregulating the MUC2 gene while altering patient's microbiota (Sibila et al., Annals of the American Thoracic Society, 2016). These results are expected to have a positive translational impact because this bottom‐up strategy would be instrumental in developing Vitamin C and B3 based orally available therapeutic strategies and formula for advancing the fields of gastrointestinal regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Vitamin C and B₃ as new biomaterials to alter intestinal stem cells

Lohman

Bratlie

et al. 2019

J Biomedical Materials Res

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“…The innate immune receptors, pattern recognition receptors (PRRs), are the key factors to trigger the inflammatory response [5]. In addition to regulating inflammation development, some PRRs also play an important role in the process of cell proliferation and apoptosis [6]. These receptors mainly include Toll like receptors (TLRs), Nod-like receptor (NLRs), RIG-I like receptor (RLRs), AIM2 like receptor (ALRs), and C-type lectin receptor (CLRs).…”

Section: Introductionmentioning

confidence: 99%

DNA sensors, crucial receptors to resist pathogens, are deregulated in colorectal cancer and associated with initiation and progression of the disease

He¹,

Liu²,

Lai³

et al. 2020

J. Cancer

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Background: DNA sensors are innate immune receptors that detect intracellular endogenous or exogenous DNA. They are critical to trigger immune response against DNA viral and intracellular bacterial infection, and are involved in inflammatory diseases and tumorigenesis. Recent accumulating evidences indicated that DNA sensors are also crucial for controlling the development of colorectal cancer (CRC). However, a systematic study on the expression profile of DNA sensors in CRC and their clinical significance are still lacking. Methods: We investigated the expression profile of DNA sensors in CRC and their clinical significance by taking advantage of clinical CRC samples, mouse AOM/DSS treatment model, and Oncomine ® bioinformatics platform. Results: Our study identified that the expression of DNA sensors, including AIM2, DAI, as well as inflammasome molecules ASC/IL-18, TLR9 and adaptor MyD88, and DDX60 decreased in human CRC, whereas the expression of DHX9, DHX36, and DDX41 significantly increased. Among them, the expression of AIM2/ASC/IL-18, MyD88, DAI, DHX36, and DDX60 were associated with cancer stages. In addition, we also performed correlation analysis between DNA sensors and their main signaling molecules to explore the possible mechanisms. The results showed that there were positive correlations between AIM2 and ASC/IL-18, DHX9 and MAVS, and TLR9 and MyD88 expression. In addition, the gene expression patterns of some DNA sensors were confirmed by Western-blot analysis. Conclusions: Our study revealed that the expression of multiple DNA sensors was deregulated in CRC and might be involved in tumor development. More importantly, the study identified that, among all these DNA sensors, AIM2, DAI, and DDX60 could be potentially critical for diagnosis, prognosis, and therapy of CRC and deserve further investigation.

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“…In particular, NLRP3 and NLRC4 sense a variety of enteric pathogens and pathobionts and initiate immune responses against these pathogens. 7, 8, 9 In addition, several ASC-containing inflammasomes are involved in the maintenance of intestinal homeostasis and the prevention of dysbiosis; consequently, they are also involved in the pathology of IBD and colitis-linked colorectal cancer. 3, 4, 10 Initial studies suggested that inflammasome activation and the production of downstream effectors is detrimental for colitis.…”

Section: Introductionmentioning

confidence: 99%

The AIM2 inflammasome is a central regulator of intestinal homeostasis through the IL-18/IL-22/STAT3 pathway

et al. 2016

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Inflammasomes are important for maintaining intestinal homeostasis, and dysbiosis contributes to the pathology of inflammatory bowel disease (IBD) and increases the risk for colorectal cancer. Inflammasome defects contribute to chronic intestinal inflammation and increase the susceptibility to colitis in mice. However, the inflammasome sensor absent in melanoma 2 (AIM2) protects against colorectal cancer in an inflammasome-independent manner through DNA-dependent protein kinase and Akt pathways. Yet, the roles of the AIM2 inflammasome in IBD and the early phases of colorectal cancer remain ill-defined. Here we show that the AIM2 inflammasome has a protective role in the intestine. During steady state, Aim2 deletion results in the loss of IL-18 secretion, suppression of the IL-22 binding protein (IL-22BP) in intestinal epithelial cells and consequent loss of the STAT3-dependent antimicrobial peptides (AMPs) Reg3β and Reg3γ, which promotes dysbiosis-linked colitis. During dextran sulfate sodium-induced colitis, a dysfunctional IL-18/IL-22BP pathway in Aim2−/− mice promotes excessive IL-22 production and elevated STAT3 activation. Aim2−/− mice further exhibit sustained STAT3 and Akt activation during the resolution of colitis fueled by enhanced Reg3b and Reg3g expression. This self-perpetuating mechanism promotes proliferation of intestinal crypt cells and likely contributes to the recently described increase in susceptibility of Aim2−/− mice to colorectal cancer. Collectively, our results demonstrate a central role for the AIM2 inflammasome in preventing dysbiosis and intestinal inflammation through regulation of the IL-18/IL-22BP/IL-22 and STAT3 pathway and expression of select AMPs.

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NOD-Like Receptors in Intestinal Homeostasis and Epithelial Tissue Repair

Cited by 65 publications

References 291 publications

Vitamin C and B₃ as new biomaterials to alter intestinal stem cells

Vitamin C and B₃ as new biomaterials to alter intestinal stem cells

DNA sensors, crucial receptors to resist pathogens, are deregulated in colorectal cancer and associated with initiation and progression of the disease

The AIM2 inflammasome is a central regulator of intestinal homeostasis through the IL-18/IL-22/STAT3 pathway

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NOD-Like Receptors in Intestinal Homeostasis and Epithelial Tissue Repair

Cited by 65 publications

References 291 publications

Vitamin C and B3 as new biomaterials to alter intestinal stem cells

Vitamin C and B3 as new biomaterials to alter intestinal stem cells

DNA sensors, crucial receptors to resist pathogens, are deregulated in colorectal cancer and associated with initiation and progression of the disease

The AIM2 inflammasome is a central regulator of intestinal homeostasis through the IL-18/IL-22/STAT3 pathway

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Vitamin C and B₃ as new biomaterials to alter intestinal stem cells

Vitamin C and B₃ as new biomaterials to alter intestinal stem cells