Rutin (22) reportedly reduces the levels of ROS, MDA, NLRP3 (NLR family
pyrin domain containing 3), ASC (apoptosis-associated speck-like protein containing a CARD), caspase-1, IL-1[beta], and IL-18 and attenuates histologic alteration as well as improving locomotion recovery [200].
Indeed, mtDNA acts as a Danger-Associated Molecular Pattern (DAMP) in animal models of sepsis [34] and triggers both intracellular inflammasome activation (through NOD-like receptor family,
pyrin domain containing 3, NLRP3 [35]) and remote organ injury (through Toll-like receptor 9 (TLR9) binding [36]).
(4,5)
Pyrin protein acts as a regulator of the inflammatory response in innate immune system.
(29,30) ATP stimulates purinergic receptor P2X7, which activates NOD-, leucine rich region repeat (LRR)-, and
pyrin domain-containing 3 (NLRP3).
These include the NOD-like receptor family,
pyrin domain containing 3 (NLRP3) inflammasome, autophagy-related 16-like 1 (ATG16L1), immunity-related GTPase family M protein (IRGM), and others, which are summarized in Table 1.
The disease is caused by mutations in the MEFV gene, which encodes a protein called
pyrin.
Pyrin is involved in inflammatory pathways (1).
The gene associated with FMF, MEFV, which encodes pyrin/marenostrin, a protein of 781 amino acids (12,13), belongs to the
pyrin family of genes that play a role in autoinflammatory diseases and inflammatory pathways (14,15).
Majority of patients with FMF have two homozygous or compound heterozygous mutations in the Mediterranean fever (MEFV) gene, which encodes the
pyrin protein (4, 5).
Based on the structural features, sensors can be classified into three types: NOD-like receptors (NLRs), AIM2-like receptors (ALRs), and
pyrin. The sensors have the ability to detect pathogen-associated molecular patterns (PAMPs) [6] or damage-associated molecular patterns (DAMPs) and cytosolic double-stranded DNA [7].
Kienes et al., "The NLR family
pyrin domain-containing 11 protein contributes to the regulation of inflammatory signaling," Journal of Biological Chemistry, vol.
Upon sensing stimuli, NLRP3 nucleotide-binding domain (NBD) oligomerizes the
pyrin domain (PYD), which serves to nucleate apoptosis-associated speck-like protein containing a CARD (ASC) proteins through PYD-PYD interactions.
Inflammasomes, multiprotein complexes consisting of proinflammatory caspase, nucleotide-binding oligomerization domain-like receptor family members containing
pyrin domain (NLRP), and the adaptor molecule apoptosisassociated speck-like protein, have proved their vital role in the process of the generation of the IL-1[beta] [10, 11].
