Regulatory Role of Non-canonical Inflammasomes in AtherosclerosisAuthor: Young-Su Yi
Inflammation is an innate immune response consisting of a series of complex biological processes to protect our body from the invading pathogens, such as bacteria, viruses, fungi, parasites and protozoan’s and cellular danger signals and is characterized by redness, heat, swelling, pain and loss of functions [1,2]. Although inflammation is a host defense mechanism, the repeated and prolonged inflammation, known as chronic inflammation, has been considered as one of the major critical risks to cause a variety of human diseases, including inflammatory autoimmune diseases, cardiovascular diseases, neuronal diseases, degenerative diseases and even cancers . Therefore, enormous efforts have been made to demonstrate the molecular and cellular mechanism of inflammatory responses in inflammatory cells and to develop various strategies modulating inflammatory responses to cure inflammation-mediated human diseases. Inflammatory response is initiated through recognizing Pathogen-Associated Molecular Patterns (PAMPs) and Danger-Associated Molecular Patterns (DAMPs) by Pattern Recognition Receptors (PRRs) expressed on the cell surfaces or inside the cells . Traditionally, researches regarding the recognition of PAMPs or DAMPs and the mechanisms of inflammatory responses has largely focused on extracellular PRRs, including toll-like receptors, scavenging receptors and c-type lectins . Recent studies have demonstrated that inflammatory responses are induced by intracellular PRRs, such as nucleotide-binding oligomerization Domain-Like Receptors (NLRs) and Absent in Melanoma 2 (AIM2) inflammasomes as well as caspase-4, -5 and -11 by assembling inflammasomes, an intracellular protein complexes consisting of PRRs and inflammatory effector molecules, such as pro-caspase-1 and an bipartite adaptor molecule, ASC [6,7]. The activation of inflammasomes subsequently induces maturation and activation of pro-caspase-1, resulting in Gasdermin-D (GSDMD)-mediated pyroptosis, an inflammatory form of apoptotic cell death and the secretion of pro-inflammatory cytokines, such as IL-1β and IL-18 [6,7].