scholarly journals Focus on the Role of NLRP3 Inflammasome in Diseases

2020 ◽  
Vol 21 (12) ◽  
pp. 4223 ◽  
Author(s):  
Roberta Fusco ◽  
Rosalba Siracusa ◽  
Tiziana Genovese ◽  
Salvatore Cuzzocrea ◽  
Rosanna Di Paola
Keyword(s):  
Immune System ◽  
Nlrp3 Inflammasome ◽  
Neurologic Disorders ◽  
Evolutionarily Conserved ◽  
The Family ◽  
Bowel Diseases ◽  
Protective Reaction ◽  
Inflammatory Bowel

Inflammation is a protective reaction activated in response to detrimental stimuli, such as dead cells, irritants or pathogens, by the evolutionarily conserved immune system and is regulated by the host. The inflammasomes are recognized as innate immune system sensors and receptors that manage the activation of caspase-1 and stimulate inflammation response. They have been associated with several inflammatory disorders. The NLRP3 inflammasome is the most well characterized. It is so called because NLRP3 belongs to the family of nucleotide-binding and oligomerization domain-like receptors (NLRs). Recent evidence has greatly improved our understanding of the mechanisms by which the NLRP3 inflammasome is activated. Additionally, increasing data in animal models, supported by human studies, strongly implicate the involvement of the inflammasome in the initiation or progression of disorders with a high impact on public health, such as metabolic pathologies (obesity, type 2 diabetes, atherosclerosis), cardiovascular diseases (ischemic and non-ischemic heart disease), inflammatory issues (liver diseases, inflammatory bowel diseases, gut microbiome, rheumatoid arthritis) and neurologic disorders (Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis and other neurological disorders), compared to other molecular platforms. This review will provide a focus on the available knowledge about the NLRP3 inflammasome role in these pathologies and describe the balance between the activation of the harmful and beneficial inflammasome so that new therapies can be created for patients with these diseases.

scholarly journals CD1d1 intrinsic signaling in macrophages controls NLRP3 inflammasome expression during inflammation

2020 ◽  
Vol 6 (43) ◽  
pp. eaaz7290
Author(s):  
Shan Cui ◽  
Chenhui Wang ◽  
Weizhi Bai ◽  
Jiao Li ◽  
Yue Pan ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Epithelial Proliferation ◽  
Intrinsic Signals ◽  
Peroxiredoxin 1 ◽  
Natural Ligand ◽  
Transcriptional Inhibition ◽  
Bowel Diseases ◽  
Lipid Antigen ◽  
Inflammatory Bowel

Dysregulation of immune responses in the gut often associates with inflammatory bowel diseases (IBD). Mouse CD1d1, an ortholog of human CD1d mainly participating in lipid-antigen presentation to NKT cells, is able to generate intrinsic signals upon stimulation. Mice with macrophage-specific CD1d1 deficiency (LymCD1d1−/−) acquire resistance to dextran sodium sulfate (DSS)–induced colitis, attributing to the transcriptional inhibition of NLRP3 inflammasome components. The hyperactivation of NLRP3 inflammasome accounts for gut epithelial proliferation and intestine-blood barrier integrity. Mechanistically, occupancy by the natural ligand glycosphingolipid iGb3, CD1d1 responds with intracellular Ser330 dephosphorylation thus to reduce the Peroxiredoxin 1 (PRDX1)–associated AKT-STAT1 phosphorylation and subsequent NF-κB activation, eventually causing transcriptional down-regulation of Nlrp3 and its immediate substrates Il1b and Il18 in macrophages. Therefore, the counterbalancing role of CD1d1 in macrophages appears to determine severity of DSS-mediated colitis in mice. These findings propose new intervention strategies for treating IBD and other inflammatory disorders.

scholarly journals Role of NLRP3 inflammasome in inflammatory bowel diseases

2019 ◽  
Vol 25 (33) ◽  
pp. 4796-4804 ◽  
Author(s):  
Evanthia Tourkochristou ◽  
Ioanna Aggeletopoulou ◽  
Christos Konstantakis ◽  
Christos Triantos
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Nlrp3 Inflammasome ◽  
Bowel Diseases ◽  
Inflammatory Bowel

scholarly journals Host–microbe interactions in the gut: lessons learned from models of inflammatory bowel diseases

2014 ◽  
Vol 1 (2) ◽  
pp. 61-76
Author(s):  
Eytan Wine
Keyword(s):  
Immune System ◽  
Animal Models ◽  
Patient Care ◽  
Inflammatory Bowel Diseases ◽  
Gut Microbes ◽  
Bowel Diseases ◽  
Microbe Interactions ◽  
Inflammatory Bowel ◽  
Host Microbe Interactions

The mammalian gut is the richest immune organ in the body and serves as a central location for immune system development, processing, and education. Inflammatory bowel diseases (IBD) provide excellent models for studying both innate and adaptive responses to gut microbes and the host-immune system – microbe interactions in the gut. Microbes are linked to almost all of the known disease-associated genetic polymorphisms in IBD and are critical mediators of environmental effects (through food, hygiene, and infection). Human and animal-based research supports the central role of microbes in IBD pathogenesis at multiple levels. Animal models of IBD only develop in the presence of microbes, and co-housing mice that are genetically susceptible to gut inflammation with normal mice can lead to the development of bowel injury. Recent advances in research technologies, such as deep-sequencing that enables detailed compositional analyses, have revolutionized the study of host–microbe interactions in the gut; however, knowing which bacteria are present in the bowel is likely not sufficient. The function of the microbiota as a community is recognized as a critical factor for gut homeostasis. Animal models of IBD have provided critical insight into basic biology and disease pathogenesis, especially regarding the role of microbes in IBD pathogenesis. Although many of these recent discoveries on host–microbe interactions are not yet applied to patient care, these basic observations will certainly revolutionize patient care in the future. Using such data, we may be able to predict risk of disease, define biological subtypes, establish tools for prevention, and even cure IBD using microbes or their products. A broad spectrum of therapeutic tools spanning from fecal transplantation, probiotics, prebiotics, and microbial products to microbe-tailored diets may supplement current IBD treatments.

Gut Mycobiota and Fungal Metabolites in Human Homeostasis

2018 ◽  
Vol 20 (2) ◽  
pp. 232-240 ◽  
Author(s):  
Izabella Mogilnicka ◽  
Marcin Ufnal
Keyword(s):  
Wide Spectrum ◽  
Biological Effects ◽  
Fungal Species ◽  
Fungal Metabolites ◽  
Human Gut ◽  
Fecal Transplantation ◽  
Bacterial Microbiota ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Background:Accumulating evidence suggests that microbiota play an important role in host’s homeostasis. Thus far, researchers have mostly focused on the role of bacterial microbiota. However, human gut is a habitat for several fungal species, which produce numerous metabolites. Furthermore, various types of food and beverages are rich in a wide spectrum of fungi and their metabolites.Methods:We searched PUBMED and Google Scholar databases to identify clinical and pre-clinical studies on fungal metabolites, composition of human mycobiota and fungal dysbiosis.Results:Fungal metabolites may serve as signaling molecules and exert significant biological effects including trophic, anti-inflammatory or antibacterial actions. Finally, research suggests an association between shifts in gut fungi composition and human health. Changes in mycobiota composition have been found in obesity, hepatitis and inflammatory bowel diseases.Conclusion:The influence of mycobiota and dietary fungi on homeostasis in mammals suggests a pharmacotherapeutic potential of modulating the mycobiota which may include treatment with probiotics and fecal transplantation. Furthermore, antibacterial action of fungi-derived molecules may be considered as a substitution for currently used antibacterial agents and preservatives in food industry.

Role of MicroRNAs in Colon Cancer Progression and Metastasis

2020 ◽  
Vol 20 ◽  
Author(s):  
Shruthi Sanjitha Sampath ◽  
Sivaramakrishnan Venkatabalsubramanian ◽  
Satish Ramalingam
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Tumour Progression ◽  
Intestinal Barrier ◽  
Colon Cancer Progression ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Novel Therapeutic Strategies

: MicroRNAs regulate gene expression at the posttranscriptional level by binding to the mRNA of their target genes. The dysfunction of miRNAs is strongly associated with the inflammation of the colon. Besides, some microRNAs are shown to suppress tumours while others promote tumour progression and metastasis. Inflammatory bowel diseases include Crohn’s disease and Ulcerative colitis which increase the risk factor for inflammation-associated colon cancer. MicroRNAs are shown to be involved in gastrointestinal pathologies, by targeting the transcripts encoding proteins of the intestinal barrier and their regulators that are associated with inflammation and colon cancer. Detection of these microRNAs in the blood, serum, tissues, faecal matter, etc will enable us to use these microRNAs as biomarkers for early detection of the associated malignancies and design novel therapeutic strategies to overcome the same. Information on MicroRNAs can be applied for the development of targeted therapies against inflammation-mediated colon cancer.

scholarly journals The Role of Enterobacteriaceae in Gut Microbiota Dysbiosis in Inflammatory Bowel Diseases

2021 ◽  
Vol 9 (4) ◽  
pp. 697
Author(s):  
Valerio Baldelli ◽  
Franco Scaldaferri ◽  
Lorenza Putignani ◽  
Federica Del Chierico
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Inflammatory Diseases ◽  
Species Level ◽  
Unknown Etiology ◽  
Gut Dysbiosis ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Symbiotic Microbiota ◽  
Gut Microbiota Dysbiosis

Inflammatory bowel diseases (IBDs) are a group of chronic gastrointestinal inflammatory diseases with unknown etiology. There is a combination of well documented factors in their pathogenesis, including intestinal microbiota dysbiosis. The symbiotic microbiota plays important functions in the host, and the loss of beneficial microbes could favor the expansion of microbial pathobionts. In particular, the bloom of potentially harmful Proteobacteria, especially Enterobacteriaceae, has been described as enhancing the inflammatory response, as observed in IBDs. Herein, we seek to investigate the contribution of Enterobacteriaceae to IBD pathogenesis whilst considering the continuous expansion of the literature and data. Despite the mechanism of their expansion still remaining unclear, their expansion could be correlated with the increase in nitrate and oxygen levels in the inflamed gut and with the bile acid dysmetabolism described in IBD patients. Furthermore, in several Enterobacteriaceae studies conducted at a species level, it has been suggested that some adherent-invasive Escherichia coli (AIEC) play an important role in IBD pathogenesis. Overall, this review highlights the pivotal role played by Enterobacteriaceae in gut dysbiosis associated with IBD pathogenesis and progression.

scholarly journals Functions of Dendritic Cells and Its Association with Intestinal Diseases

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 583
Author(s):  
Ze-Jun Yang ◽  
Bo-Ya Wang ◽  
Tian-Tian Wang ◽  
Fei-Fei Wang ◽  
Yue-Xin Guo ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dendritic Cells ◽  
Immune System ◽  
Regulatory Mechanism ◽  
Intestinal Tumors ◽  
Regulatory Relationship ◽  
Intestinal Diseases ◽  
Inflammatory Bowel ◽  
Plasmacytoid Dcs

Dendritic cells (DCs), including conventional DCs (cDCs) and plasmacytoid DCs (pDCs), serve as the sentinel cells of the immune system and are responsible for presenting antigen information. Moreover, the role of DCs derived from monocytes (moDCs) in the development of inflammation has been emphasized. Several studies have shown that the function of DCs can be influenced by gut microbes including gut bacteria and viruses. Abnormal changes/reactions in intestinal DCs are potentially associated with diseases such as inflammatory bowel disease (IBD) and intestinal tumors, allowing DCs to be a new target for the treatment of these diseases. In this review, we summarized the physiological functions of DCs in the intestinal micro-environment, their regulatory relationship with intestinal microorganisms and their regulatory mechanism in intestinal diseases.

scholarly journals The role of epigenetic modifications for the pathogenesis of Crohn's disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
M. Hornschuh ◽  
E. Wirthgen ◽  
M. Wolfien ◽  
K. P. Singh ◽  
O. Wolkenhauer ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
New Biomarkers ◽  
Insight Into ◽  
Specific Evaluation

AbstractEpigenetics has become a promising field for finding new biomarkers and improving diagnosis, prognosis, and drug response in inflammatory bowel disease. The number of people suffering from inflammatory bowel diseases, especially Crohn's disease, has increased remarkably. Crohn's disease is assumed to be the result of a complex interplay between genetic susceptibility, environmental factors, and altered intestinal microbiota, leading to dysregulation of the innate and adaptive immune response. While many genetic variants have been identified to be associated with Crohn's disease, less is known about the influence of epigenetics in the pathogenesis of this disease. In this review, we provide an overview of current epigenetic studies in Crohn's disease. In particular, we enable a deeper insight into applied bioanalytical and computational tools, as well as a comprehensive update toward the cell-specific evaluation of DNA methylation and histone modifications.

Sign in / Sign up

Export Citation Format

Share Document