Importantly, TLR4 signaling is required for the activation of the inflammasome
(Bauernfeind et al.
The response of tissue macrophages to crystals involves the activation of the NALP3 inflammasome
, a multimolecular complex that employs the enzyme caspase 1 to convert the pro-form of IL-1[beta] into the active form (Fig.
NASDAQ: IDRA) today announced new data from preclinical studies showing that selective inhibition of Toll-like Receptors (TLRs) 7, 8, and 9, which play a key role in inflammation and immunity, also resulted in inhibition of inflammasome
activation and induction of Interleukin 1 beta (IL-1), a pro-inflammatory cytokine that has been shown to be involved in Beh[?
Despite the important role of IL-1 in host defence against infection, dysregulated inflammasome
activation and IL-1 production has a causal role in a number of acquired and hereditary auto-inflammatory conditions.
Spleen tyrosine kinase (Syk) is involved in the development of the adaptive immune system and has been recognized as being important in the function of additional cell types, including platelets, phagocytes, fibroblasts, and osteoclasts, and in the generation of the inflammasome
Recent studies have provided insights into the mechanisms through which uric acid crystals activate macrophages, in particular, the role of the NALP3 (NACHT, LRR and pyrin domain-containing protein) inflammasome
Signaling Lessons from Death Receptors: the Inflammasome
2008b) and evaluation of the Nod-like receptor protein 3 (NLRP3) inflammasome
activation with THP-1 cells (Hamilton et al.
In this study, researchers showed IL-18 produced by the Nlrp3 inflammasome
helped mice maintain healthy colon by triggering production of more epithelial cells to compensate for those damaged or destroyed by colitis.
17) Gouty inflammation is driven extracellularly by recognition and uptake of urate crystals by the Toll-like receptors TLR2 and TLR4 (18,19) and intracellularly by the pattern recognition receptor NALP3 (cryopyrin) in an inflammasome
protein complex that stimulates caspase-1 activation, with consequent IL-1[beta]-driven inflammation (20) mediated in part by the TLR and IL-1 receptor adaptor protein MyD88.
protein complex is an important regulator of IL-1[beta] and IL-18 maturation and release into the extracellular space (reviewed by Hoffman and Brydges 2011; Jin and Flavell 2010).
Epigallocatechin-3-gallate prevents lupus nephritis development in mice via enhancing the Nrf2 antioxidant pathway and inhibiting NLRP3 inflammasome