Abstract
Aberrant NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome activation in innate immune cells, triggered by diverse cellular danger signals, leads to the production of inflammatory cytokines (IL-1β and IL-18) and cell death by pyroptosis. These processes are involved in the pathogenesis of a wide range of diseases such as autoimmune, neurodegenerative, renal, metabolic, vascular diseases and cancer, and during physiological processes such as aging. Epigenetic dynamics mediated by changes in DNA methylation patterns, chromatin assembly and non-coding RNA expression are key regulators of the expression of inflammasome components and its further activation. Here, we review the role of the epigenome in the expression, assembly, and activation of the NLRP3 inflammasome, providing a critical overview of its involvement in the disease and discussing how targeting these mechanisms by epigenetic treatments could be a useful strategy for controlling NLRP3-related inflammatory diseases.
Highlights
Inflammation-Related Processes.Inflammation is a defense mechanism developed by our own immune system to fight infections, endogenous signals and tissue damage, and to restore cellular homeostasis
NLRP3 inflammasome activation initiates an inflammatory response that, when constant and persistent over time, produces a chronic inflammatory state that is difficult to reverse and that aggravates the outcome of many inflammationrelated diseases
Activation of the NLRP3 inflammasome affects the development of a wide range of diseases but is crucial to the host’s defense against bacterial infections and to the elimination of tumors
Summary
Inflammasomes are multiprotein complexes located within those innate immune cells that act as central nodules of the inflammatory response [1] They can sense the danger signals, integrate them in the cell and respond by producing specific pro-inflammatory cytokines (IL-1β and IL-18) and a caspase-dependent form of cell death called pyroptosis. We will review the epigenetic mechanisms (DNA methylation, histone modifications and miRNAs) that are directly or indirectly involved in the expression of the components of NLRP3 inflammasome and the consequences of their modulation Understanding these mechanisms highlights the potential value of epigenetic drugs for treating chronic inflammatory diseases in which NLRP3 inflammasome activation plays an essential role
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