Negative regulation of NLRP3 inflammasome signaling

Abstract

Infl ammasomes are multiprotein complexes that serve as a platform for caspase-1 activation and interleukin-1β (IL-1β) maturation as well as pyroptosis. Though a number of infl ammasomes have been described, the NLRP3 infl ammasome is the most extensively studied. NLRP3 infl ammasome is triggered by a variety of stimuli, including infection, tissue damage and metabolic dysregulation, and then activated through an integrated cellular signal. Many regulatory mechanisms have been identifi ed to attenuate NLRP3 infl ammasome signaling at multiple steps. Here, we review the developments in the negative regulation of NLRP3 inflammasome that protect host from inflammatory damage.

Inflammasome Priming in Sterile Inflammatory Disease

“…For example, miRNA-223 has been shown to suppress NLRPγ priming by binding to a conserved site in the γ′-untranslated region (UTR) of the NLRP3 transcript, thereby reducing downstream signaling [145,146,147] . In addition, inhibition of several other miRNAs involved in NLRP3 activation, miR115, miR133a-1, and miR-377, may be beneficial for suppression of NLRP3 function [148,149,150].…”

Cell death offers exceptional cellular and molecular windows for pharmacological interventions in protozoan parasites

“…In addition, recent research work shows the implication of inflammasomes in the induction of programmed cell death, such as apoptosis via recruit procaspase-8 [107]. Inflammasomes have now been described in details, and are reviewed elsewhere [108][109][110][111]. Inflammasomes counter parasite replication and clear infected cells through an inflammatory cell death program termed pyroptosis.…”

NLRP3 Inflammasome Activation Is Essential for Paraquat-Induced Acute Lung Injury

“…The NLRP3 inflammasome, one of the inflammasome complexes, has a basic structure consisting of nucleotide-binding-domain, leucine-rich repeat domain containing protein (NLRP), and the adaptor protein ASC (apoptosis-associated speck-like protein containing caspase-1 activator domain), which recruit and activate procaspase-1 [7]. The NLRP3 inflammasome is expressed in many inflammatory cells, including macrophages and neutrophils, and also activated by many factors including environmental irritants, endogenous danger signals, pathogens, and distinct pathogenassociated molecular patterns (PAMPs) [8,9]. Moreover, it is proposed that a lot of the cellular signals are responsible for NLRP3 activation, including potassium (K + ) efflux, pore formation in cell membranes, lyposomes damage, the elevation of ROS, and damage in the mitochondria [9][10][11].…”

“…The NLRP3 inflammasome is expressed in many inflammatory cells, including macrophages and neutrophils, and also activated by many factors including environmental irritants, endogenous danger signals, pathogens, and distinct pathogenassociated molecular patterns (PAMPs) [8,9]. Moreover, it is proposed that a lot of the cellular signals are responsible for NLRP3 activation, including potassium (K + ) efflux, pore formation in cell membranes, lyposomes damage, the elevation of ROS, and damage in the mitochondria [9][10][11].…”