scholarly journals Inflammasome Regulation: Therapeutic Potential for Inflammatory Bowel Disease

Molecules ◽  
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.

scholarly journals The Multifaceted Role of the Inflammasome in Inflammatory Bowel Diseases

2011 ◽  
Vol 11 ◽  
pp. 1536-1547 ◽  
Author(s):  
Donata Lissner ◽  
Britta Siegmund
Keyword(s):  
Inflammatory Bowel Disease ◽  
Inflammatory Bowel Diseases ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Inflammasome Activation ◽  
Specific Cell ◽  
Epithelial Regeneration ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammasomes are intracellular multiprotein complexes that coordinate the maturation of interleukin (IL)-1β and IL-18 in response to pathogens and metabolic danger. Both cytokines have been linked to intestinal inflammation. However, recently evolving concepts ascribe a major role to the inflammasome in maintaining intestinal homeostasis. This review recapitulates its position in the development of inflammatory bowel disease, thereby outlining a model in which hypo- as well as hyperfunctionality can lead to an imbalance of the system, depending on the specific cell population affected. In the epithelium, the inflammasome is essential for regulation of permeability and epithelial regeneration through sensing of commensal microbes, while excessive inflammasome activation within the lamina propria contributes to severe intestinal inflammation.

scholarly journals PPARγin Inflammatory Bowel Disease

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
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.

scholarly journals ADP/P2Y1 aggravates inflammatory bowel disease through ERK5-mediated NLRP3 inflammasome activation

2020 ◽  
Vol 13 (6) ◽  
pp. 931-945
Author(s):  
Chengfei Zhang ◽  
Juliang Qin ◽  
Su Zhang ◽  
Na Zhang ◽  
Binhe Tan ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Inflammatory Bowel

The Role of Peroxisome Proliferator–Activated Receptor γ in Colon Cancer and Inflammatory Bowel Disease

2003 ◽  
Vol 127 (9) ◽  
pp. 1121-1123
Author(s):  
Arthur W. Bull
Keyword(s):  
Inflammatory Bowel Disease ◽  
Colon Cancer ◽  
Bowel Disease ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Inflammatory Bowel

Abstract Objective.—Review the role and therapeutic potential of peroxisome proliferator–activated receptor (PPAR) γ in colonic disorders. Data Sources.—Recent peer-reviewed scientific literature focusing on PPAR γ in the colon. Study Selection.—Research reports using animal models, cultured cell lines, and clinical material were examined for content related to the role of PPAR γ in normal colon cell function, colon cancer, and inflammatory bowel disease. Issues concerned with potential therapeutic use were also considered. Data Synthesis.—Key points pertaining to PPAR function and involvement in colon pathology were extracted and noted. Potential compromises to therapeutic utility are identified. Conclusions.—The emerging important role of PPAR γ in normal tissue homeostasis and pathologic outcomes suggests this receptor is a good candidate as a drug target. Several potential problems with this approach will require further investigation prior to widespread recommendations for modulation of PPAR as an efficacious therapy for cancer, chemoprevention of colon cancer, or treatment of inflammatory bowel disease. The widespread use of PPAR γ ligands for management of type 2 diabetes (such as the glitazone class of drugs including rosiglitazone and pioglitazone) may provide a fortuitous assessment of the efficacy of long-term PPAR modulation.

Isoorientin Alleviates Inflammatory Bowel Disease by Inhibiting NLRP3 Inflammasome Activation through Nrf2/NQO1 Pathway

2020 ◽  
Vol 18 (4) ◽  
pp. 392-397
Author(s):  
Qirun Cheng ◽  
Xianjin Yu ◽  
Rong Zhang ◽  
Lipeng Chen
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Sulfonic Acid ◽  
Tissue Injury ◽  
Biological Activities ◽  
Trinitrobenzene Sulfonic Acid ◽  
Inflammasome Activation ◽  
Nucleotide Binding Domain ◽  
Nlrp3 Inflammasome Activation ◽  
Inflammatory Bowel

Inflammatory bowel disease comprises a series of related conditions characterized by idiopathic inflammation of the gastrointestinal tract. To develop therapeutic agents to combat these conditions, a better understanding of the inflammatory mechanisms is of paramount importance. Isoorientin is a c-glycosylflavone common to plants such as Phyllostachys japonicus and buckwheat. While it has been documented to exhibit multiple biological activities, its effects on inflammatory bowel disease, and the potential regulatory mechanism remain to be explored. We have shown here that isoorientin relieves the intestinal tissue injury and decreases the activity and expression of myeloperoxidase in trinitrobenzene sulfonic acid-exposed rats. Furthermore, isoorientin alleviated cytokine secretion in rats after trinitrobenzene sulfonic acid exposure. Also, isoorientin suppressed the levels of the nucleotide-binding domain and leucine-rich repeat-containing protein family and enhanced the Nrf2/NQO1 pathway in trinitrobenzene sulfonic acid-induced bowel disease. In conclusion, isoorientin could serve as a promising drug for the treatment of chronic enteritis.

scholarly journals The Functions and Therapeutic Potential of Heat Shock Proteins in Inflammatory Bowel Disease—An Update

2019 ◽  
Vol 20 (21) ◽  
pp. 5331 ◽  
Author(s):  
Abdullah Hoter ◽  
Hassan Y. Naim
Keyword(s):  
Inflammatory Bowel Disease ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Bowel Disease ◽  
Therapeutic Potential ◽  
Inflammatory Bowel ◽  
Targeted Inhibition ◽  
Shock Proteins ◽  
Lines Of Evidence

Inflammatory bowel disease (IBD) is a multifactorial human intestinal disease that arises from numerous, yet incompletely defined, factors. Two main forms, Crohn’s disease (CD) and ulcerative colitis (UC), lead to a chronic pathological form. Heat shock proteins (HSPs) are stress-responsive molecules involved in various pathophysiological processes. Several lines of evidence link the expression of HSPs to the development and prognosis of IBD. HSP90, HSP70 and HSP60 have been reported to contribute to IBD in different aspects. Moreover, induction and/or targeted inhibition of specific HSPs have been suggested to ameliorate the disease consequences. In the present review, we shed the light on the role of HSPs in IBD and their targeting to prevent further disease progression.

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

Cells ◽  
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.

scholarly journals Contradictory Effects of NLRP3 Inflammasome Regulatory Mechanisms in Colitis

2020 ◽  
Vol 21 (21) ◽  
pp. 8145
Author(s):  
Kohei Wagatsuma ◽  
Hiroshi Nakase
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Nlrp3 Inflammasome ◽  
Experimental Colitis ◽  
Regulatory Mechanisms ◽  
Pyrin Domain ◽  
Complex Interactions ◽  
Inflammatory Bowel ◽  
Receptor Family

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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