The immunomodulatory molecule pidotimod induces the expression of the NOD-like receptor NLRP12
and attenuates TLR-induced inflammation.
Exons 1-9 of nucleotide-bind domain and leucine-rich repeat containing family pyrin-domain containing ( NLRP ) 3 gene and exon 3 of NLRP12
were amplified by polymerase chain reaction (PCR).
The NLR family, pyrin domain-containing 1 , 3 , 4 , and 12  (NLRP1, NLRP3, NLRP4, and NLRP12
, resp.), are NLRs that have been shown to be involved in inflammasome assembly, while AIM2 is the most well-characterized ALR.
There have been seven established NLRs that form an inflammasome complex: NLRP1 (NALP1), NLRP3 (NALP3 or cryopyrin), NLRP6, NLRP12
, NLRC4 (with caspase recruitment domain or IPAF), AIM2 (absent in melanoma-2), and RIG-1 (retinoic acid inducible gene-1); however, the NLRP3 inflammasome is the best characterized in relation with renal diseases .
Each NLR molecule (NLRP1, NLRP3, NLRP6, NLRP7, NLRP12
, or NAIP/NLRC4) recognizes specific ligands that activate the assembly of the inflammasome.
ATP binding by monarch-1/ NLRP12
is critical for its inhibitory function.
Investigators showed that the protein NLRP12
works in T cells to limit production of chemical messengers or cytokines that fuel inflammation.
Con respecto a las NLRs, son una familia de 23 proteinas codificadas en el genoma humano, las cuales contienen un dominio de union de nucleotidos y un dominio repetido rico en leucina (que incluye: NALP, NOD, PYPAF y CATERPILLER); hasta ahora, se han identificado 8 miembros de estas 23 proteinas con capacidad para formar los inflamasomas, a saber: la proteina NLRP1, la NLRP3, la NLRP6, la NLRP12
, la NLRP2, la NLRC4, la ALR (receptor tipo AIM-2 o ausente en melanoma 2) y el sensor citoplasmatico RIG-1.
Recently, an increasing number of papers concerning human inflammatory diseases have focused on NLRP12
, a member of the NLR gene family.
This is an autosomal dominant disease caused by mutations in the NLRP12
gene encoding for the protein NLRP12
(or "monarch-1"), which plays a crucial role in immune system mechanisms against pathogenic agents (Table 1).
In addition to NLR inflammasomes (NLRP1, NLRP3, NLRP6, NLRP12
, and NLRC4), there are four additional inflammasomes (AIM2, RIG-I, IFI6, and PYRIN) which form by non-NLR sensor proteins .