Pharmacological and genetic strategies limiting NLRP3 inflammasome activation have been shown to be beneficial in a wide range of experimental models, from common pathologies such as arthritis, cardiovascular disease, and metabolic syndromes to rare genetic disorders such as cryopyrin-associated periodic syndrome.
Glucosamine is widely used as a dietary supplement to promote the health of cartilage tissue and is expected to exert anti-inflammatory activity in joint inflammation, which is a nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome-associated complication.
In fact, above responses have been identified to be involved in the development of autoimmunity, specifically, the NLRP3 inflammasome could promote inflammation in massive autoimmune diseases and TG2, as well as cathepsin may contribute to joint destruction and degeneration in inflammatory arthritis.
Neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurologic, cutaneous, and arthritis (CINCA) syndrome is the most severe clinical phenotype in the spectrum of cryopyrin- (NLRP3/NALP3) associated periodic syndromes (CAPS).
Here, we show that ASC(-/-) mice were protected from arthritis, whereas Nlrp3(-/-) and caspase-1(-/-) mice were susceptible to collagen-induced arthritis.
Cryopyrinopathies are a group of conditions associated to mutations of the gene Cryopyrin that are responsible for a spectrum of diseases (familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological cutaneous and articular syndrome) characterized by a chronic or recurrent systemic inflammation variably associated with a number of clinical features, such as urticarial-like rash, arthritis, sensorineural deafness, and central nervous system and bone involvement.
We undertook this study to determine whether a patient with arthritis and antibiotic-resistant fever carried mutations in the genes encoding the NALP3 inflammasome.
Sequencing of six family members' CIAS1-gene exon 3 identified a heterozygous mutation, c.1043C > T. Pertinently, this CAPS is distinct from chronic infantile neurological cutaneous and arthritis syndrome/neonatal onset multisystemic inflammatory disease syndrome and Muckle-Wells syndrome (MWS), which also result from exon 3 mutations in this gene.