J Biomed Res.  2013 Dec;14(4):195-200.

Inflammasomes, multi-cellular protein complex in myeloid cells, induce several metabolic diseases via interleukin-1beta maturation

• Lee GS

Abstract

Inflammation mainly mediated by innate immune cells as the first line of host defense against pathogens is an acute response that limits tissue damage and eliminates pathogens in the body. In triggering inflammation, several pattern recognition receptors work together; membrane-associated Toll-like receptors, c-type lectin receptors, retinoic acid-inducible gene-like helicase receptors, absent in melanoma-like receptors, and cytosolic nucleotide-binding domain and leucine-rich repeat receptors. Among them, inflammasome is a newly trigger of inflammation in response to exogenous and endogenous stimuli and its activation leads to the assembly of multiprotein platforms composed of NLRP3 (NOD-like receptor family, pyrin domain containing 3), ASC (apoptosis associated speck-like protein containing a CARD), and procaspase 1. Thus, the activated inflammasome activates caspase 1, resulting in processing and secretion of interleukin (IL)-1beta. Recent emerging data suggest that dysregulated metabolites, i.e., amyloids, ceramides, and cholesterol crystals, have been classified as inflammasome activators. In addition, IL-1beta may play a critical role in the pathogenesis of chronic inflammation-induced disorders such as Alzheimer's diseases, type 2 diabetes, and atheriosclerosis. This review introduces the basic concept of inflammasome activation and auto-inflammatory diseases. In addition, it discusses the updated signaling models of inflammasome activation that link metabolic dysfunction in order to outline future therapeutic approaches to inflammasome-mediating diseases.

Keyword

inflammasome; inflammation; interleukin-1beta; macrophages; metabolic dysfunction

MeSH Terms

Amyloid
Caspase 1
Ceramides
Cholesterol
Cytosol
Humans
Inflammasomes*
Inflammation
Interleukin-1beta*
Interleukins
Lectins, C-Type
Macrophages
Metabolic Diseases*
Myeloid Cells*
Receptors, Pattern Recognition
Toll-Like Receptors
Amyloid
Caspase 1
Ceramides
Cholesterol
Inflammasomes
Interleukin-1beta
Interleukins
Lectins, C-Type
Receptors, Pattern Recognition
Toll-Like Receptors