Metabolic regulation of inflammasomes in inflammation

Abstract

Summary Inflammasome activation and subsequent inflammatory cytokine secretion are essential for innate immune defence against multiple stimuli and are regarded as a link to adaptive immune responses. Dysfunction of inflammasome activation has been discovered at the onset or progression of infectious diseases, autoimmune diseases and cancer, all of which are also associated with metabolic factors. Furthermore, many studies concerning the metabolic regulation of inflammasome activation have emerged in recent years, especially regarding the activity of the NLRP3 inflammasome under metabolic reprogramming. In this review, we discuss the molecular mechanisms of the interactions between metabolic pathways and inflammasome activation, which exerts further important effects on various diseases.

Fatigue, Sleep, and Autoimmune and Related Disorders

“…A primary mechanism that activates IL-1β occurs through the activation of inflammasomes (109). Inflammasomes are large intracellular signaling protein complexes found within the cytoplasm of most nucleated cells including neurons, astrocytes, microglia, and perivascular macrophages in the brain (Figure 1) (44, 109, 110).…”

“…A primary mechanism that activates IL-1β occurs through the activation of inflammasomes (109). Inflammasomes are large intracellular signaling protein complexes found within the cytoplasm of most nucleated cells including neurons, astrocytes, microglia, and perivascular macrophages in the brain (Figure 1) (44, 109, 110). Inflammasome activation involves a priming step and a secondary step that induces the formation of the complex to activate caspase-1 to cleave the pro-forms of IL-1β and other IL-1 family members, such as IL-18 and IL-33, into their mature active forms (111).…”

“…JNKs and MAPK/extracellular signal regulated kinase (ERK) pathways, which can activate AP-1 mediated transcription, also are implicated in the activation of inflammasomes (115). Most inflammasomes contain a nucleotide-binding oligomerization domain-like receptor or an absent in melanoma 2 (AIM2)-like receptor (109). The nucleotide leucine-rich protein-3 (NLRP3) inflammasome is the most widely characterized inflammasome, although multiple types of inflammasomes exist with unique recognition abilities in response to specific pathogen-associated molecular patterns (PAMPS) or danger-associated molecular patterns (DAMPS) (111).…”

Type III Secretion Effector VopQ of Vibrio parahaemolyticus Modulates Central Carbon Metabolism in Epithelial Cells

“…immune cells (33,34). Several studies have suggested that inflammasome activation is modulated by several glycolytic enzymes (35). For example, inhibiting hexokinase-1 or pyruvate kinase (PKM2) suppresses NLRP3 inflammasome activation in macrophages (36,37).…”

Suppression of Glucagon-Like Peptide-1 Release by Inhibition of Intestinal NLRP3 Inflammasome Activation in Asc–/– and Nlrp3–/– Mice

“…It recruits the adapter protein ASC and pro-caspase-1 leading to caspase-1 activation and subsequent secretion of interleukin-1β (IL-1β), IL-18, or high mobility group box-1 protein (HMGB1) (Kamo et al, 2013). The NLRP3 inflammasome activation instigates tissue inflammatory response and thereby plays a significant role in the development of various inflammatory diseases (Yang et al, 2019). It has been reported that the NLRP3 inflammasome senses obesity-associated inducers of caspase-1 activation and thus regulates the magnitude of inflammation and its downstream effect on insulin signaling (Vandanmagsar et al, 2011).…”