Contradictory Effects of NLRP3 Inflammasome Regulatory Mechanisms in Colitis

The inflammasome is an intracellular molecular complex, which is mainly involved in innate immunity. Inflammasomes are formed in response to danger signals, associated with infection and injury, and mainly regulate the secretion of interleukin-1β and interleukin-18. Inflammasome dysregulation is known to be associated with various diseases and conditions, and its regulatory mechanisms have become of great interest in recent years. In the colon, inflammasomes have been reported to be associated with autophagy and the microbiota, and their dysregulation contributes to colitis and. However, the detailed role of inflammasomes in inflammatory bowel disease is still under debate because the mechanisms that regulate the inflammasome are complex and the inflammasome components and cytokines show seemingly contradictory multiple effects. Herein, we comprehensively review the literature on inflammasome functioning in the colon and describe the complex interactions of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome components with inflammatory cytokines, autophagy, and the microbiota in experimental colitis models and patients with inflammatory bowel disease.

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S1716 A Positive Role of CHOP, a Transcription Factor Involved in ER Stress Response, in Development of Inflammatory Bowel Disease (IBD)-Related Experimental Colitis

Gastroenterology ◽

10.1016/s0016-5085(08)61187-7 ◽

2008 ◽

Vol 134 (4) ◽

pp. A-256

Author(s):

Takushi Namba ◽

Tohru Mizushima

Keyword(s):

Inflammatory Bowel Disease ◽

Transcription Factor ◽

Stress Response ◽

Er Stress ◽

Bowel Disease ◽

Experimental Colitis ◽

Positive Role ◽

Er Stress Response ◽

Inflammatory Bowel

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PPARγin Inflammatory Bowel Disease

PPAR Research ◽

10.1155/2012/620839 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 39

Author(s):

Vito Annese ◽

Francesca Rogai ◽

Alessia Settesoldi ◽

Siro Bagnoli

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Potential Role ◽

Intestinal Inflammation ◽

Experimental Colitis ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Beneficial Effects ◽

Inflammatory Bowel

Peroxisome proliferator-activated receptor gamma (PPARγ) is member of a family of nuclear receptors that interacts with nuclear proteins acting as coactivators and corepressors. The colon is a major tissue which expresses PPARγin epithelial cells and, to a lesser degree, in macrophages and lymphocytes and plays a role in the regulation of intestinal inflammation. Indeed, both natural and synthetic PPARγligands have beneficial effects in different models of experimental colitis, with possible implication in the therapy of inflammatory bowel disease (IBD). This paper will specifically focus on potential role of PPARγin the predisposition and physiopathology of IBD and will analyze its possible role in medical therapy.

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Inflammasome Regulation: Therapeutic Potential for Inflammatory Bowel Disease

Molecules ◽

10.3390/molecules26061725 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1725

Author(s):

Qiuyun Xu ◽

Xiaorong Zhou ◽

Warren Strober ◽

Liming Mao

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Therapeutic Potential ◽

Experimental Colitis ◽

Inflammasome Activation ◽

Nlrp3 Inflammasome Activation ◽

Genetic Abnormalities ◽

Inflammatory Bowel ◽

Inflammatory Caspases

Inflammasomes are multiprotein complexes formed to regulate the maturation of pro-inflammatory caspases, in response to intracellular or extracellular stimulants. Accumulating studies showed that the inflammasomes are implicated in the pathogenesis of inflammatory bowel disease (IBD), although their activation is not a decisive factor for the development of IBD. Inflammasomes and related cytokines play an important role in the maintenance of gut immune homeostasis, while its overactivation might induce excess immune responses and consequently cause tissue damage in the gut. Emerging studies provide evidence that some genetic abnormalities might induce enhanced NLRP3 inflammasome activation and cause colitis. In these cases, the colonic inflammation can be ameliorated by blocking NLRP3 activation or its downstream cytokine IL-1β. A number of natural products were shown to play a role in preventing colon inflammation in various experimental colitis models. On the other hand, lack of inflammasome function also causes intestinal abnormalities. Thus, an appropriate regulation of inflammasomes might be a promising therapeutic strategy for IBD intervention. This review aims at summarizing the main findings in these studies and provide an outline for further studies that might contribute to our understanding of the role of inflammasomes in the pathogenesis and therapeutic treatment of IBD.

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Role of MicroRNA in Inflammatory Bowel Disease: Clinical Evidence and the Development of Preclinical Animal Models

Cells ◽

10.3390/cells10092204 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2204

Author(s):

Kanika Suri ◽

Jason A. Bubier ◽

Michael V. Wiles ◽

Leonard D. Shultz ◽

Mansoor M. Amiji ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Animal Models ◽

Mirna Expression ◽

Bowel Disease ◽

Therapeutic Potential ◽

Genetically Engineered ◽

Complex Interactions ◽

Inflammatory Bowel ◽

Preclinical Animal Models

The dysregulation of microRNA (miRNA) is implicated in cancer, inflammation, cardiovascular disorders, drug resistance, and aging. While most researchers study miRNA’s role as a biomarker, for example, to distinguish between various sub-forms or stages of a given disease of interest, research is also ongoing to utilize these small nucleic acids as therapeutics. An example of a common pleiotropic disease that could benefit from miRNA-based therapeutics is inflammatory bowel disease (IBD), which is characterized by chronic inflammation of the small and large intestines. Due to complex interactions between multiple factors in the etiology of IBD, development of therapies that effectively maintain remission for this disease is a significant challenge. In this review, we discuss the role of dysregulated miRNA expression in the context of clinical ulcerative colitis (UC) and Crohn’s disease (CD)—the two main forms of IBD—and the various preclinical mouse models of IBD utilized to validate the therapeutic potential of targeting these miRNA. Additionally, we highlight advances in the development of genetically engineered animal models that recapitulate clinical miRNA expression and provide powerful preclinical models to assess the diagnostic and therapeutic promise of miRNA in IBD.

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The Interplay Between Genetic Risk Factors and Proteolytic Dysregulation in the Pathophysiology of Inflammatory Bowel Disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa033 ◽

2020 ◽

Vol 14 (8) ◽

pp. 1149-1161 ◽

Cited By ~ 2

Author(s):

Núria Solà-Tapias ◽

Nathalie Vergnolle ◽

Alexandre Denadai-Souza ◽

Frédérick Barreau

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Experimental Colitis ◽

Functional Proteomics ◽

Tissue Samples ◽

Intestinal Microbes ◽

Abnormal Immune Response ◽

Inflammatory Bowel ◽

Cellular Pathways

Abstract Crohn’s disease [CD] and ulcerative colitis [UC] are the two main forms of inflammatory bowel disease [IBD]. Previous studies reported increased levels of proteolytic activity in stool and tissue samples from IBD patients, whereas the re-establishment of the proteolytic balance abrogates the development of experimental colitis. Furthermore, recent data suggest that IBD occurs in genetically predisposed individuals who develop an abnormal immune response to intestinal microbes once exposed to environmental triggers. In this review, we highlight the role of proteases in IBD pathophysiology, and we showcase how the main cellular pathways associated with IBD influence proteolytic unbalance and how functional proteomics are allowing the unambiguous identification of dysregulated proteases in IBD, paving the way to the development of new protease inhibitors as a new potential treatment.

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The role of osteopontin (OPN/SSP1) gene variants in inflammatory bowel disease

Zeitschrift für Gastroenterologie ◽

10.1055/s-0029-1241334 ◽

2009 ◽

Vol 47 (09) ◽

Author(s):

J Glas ◽

J Seiderer ◽

HP Török ◽

B Göke ◽

T Ochsenkühn ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Gene Variants ◽

Inflammatory Bowel

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Nutrition in inflammatory bowel disease

Orvosi Hetilap ◽

10.1556/oh.2009.28599 ◽

2009 ◽

Vol 150 (18) ◽

pp. 839-845 ◽

Cited By ~ 2

Author(s):

János Banai

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Fast Food ◽

Optimal Growth ◽

Developed Countries ◽

Aetiological Factor ◽

Artificial Nutrition ◽

Food Preservatives ◽

Inflammatory Bowel

Aetiology of inflammatory bowel disease (IBD) is complex and probably multifactorial. Nutrition has been proposed to be an important aetiological factor for development of IBD. Several components of the diet (such as sugar, fat, fibre, fruit and vegetable, protein, fast food, preservatives etc.) were examined as possible causative agents for IBD. According to some researchers infant feeding (breast feeding) may also contribute to the development of IBD. Though the importance of environmental factors is evidenced by the increasing incidence in developed countries and in migrant population in recent decades, the aetiology of IBD remained unclear. There are many theories, but as yet no dietary approaches have been proved to reduce the risk of developing IBD. The role of nutrition in the management of IBD is better understood. The prevention and correction of malnutrition, the provision of macro- and micronutrients and vitamins and the promotion of optimal growth and development of children are key points of nutritional therapy. In active disease, the effective support of energy and nutrients is a very important part of the therapy. Natural and artificial nutrition or the combination of two can be choosen for supporting therapy of IBD. The author summarises the aetiological and therapeutic role of nutrition in IBD.

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