Initiation of an inflammatory response requires the co-ordinated participation of proteins within a scaffold in the cytosol of responding cells. The scaffold proteins contain members of a newly discovered family of pyrin-domain adaptor proteins that regulate complex assembly for initiation of nuclear factor kappaB and interleukin-1beta signalling. A paper in this issue of the Biochemical Journa...

Sir, Familial Mediterranean fever (FMF) is an auto-inflammatory disease with an autosomal recessive inheritance. Defects in the protein pyrin cause the characteristic attacks of the disease. 1,2 More than 20 mutations have been identified in the gene coding pyrin. Booth et al. 3 recently presented their studies in an interesting mutation, the E148Q mutation, in different populations. They have ...

Upon activation Nod-like receptors (NLRs) assemble into multi-protein complexes such as the NODosome and inflammasome. This process relies upon homo domain interactions between the structurally related Pyrin and caspase-recruitment (CARD) domains and adaptor proteins, such as ASC, or effector proteins, such as caspase-1. Although a variety of NLRP and NLRC complexes have been described along wi...

Zusammenfassung Das familiäre Mittelmeerfieber (FMF) ist die häufigste autoinflammatorische Erkrankung und gehört zu den monogenetischen Fiebersyndromen. Die beruht auf einer Mutation des MEFV -Gens; dieses dem kurzen Arm von Chromosom 16 lokalisiert kodiert für das Protein Pyrin. Pyrin aktiviert über mehrere Schritte eine erhöhte Ausschüttung der proinflammatorischen Zytokine Interleukin (IL)‑...

The innate immune response depends on the ability of immune cells to detect pathogens through germline-encoded pattern recognition receptors (PRRs). Recently discovered PRRs include some members of the Pyrin and HIN domain (PYHIN) family, which are encoded on an interferon-inducible gene cluster located on chromosome 1q23. There are five human PYHIN proteins; Absent in melanoma 2 (AIM2), IFN-γ ...

Microbial agents can aggravate inflammatory diseases, such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). An example is pertussis toxin (PTX), a bacterial virulence factor commonly used as an adjuvant to promote EAE, but whose mechanism of action is unclear. We have reported that PTX triggers an IL-6-mediated signaling cascade that increases th...

Familial Mediterranean Fever (FMF) is an inherited autoinflammatory disorder characterized by unprovoked episodes of fever and inflammation. The associated gene, MEFV (Mediterranean Fever), is expressed primarily by cells of myeloid lineage and encodes the protein pyrin/TRIM20/Marenostrin. The mechanism by which mutations in pyrin alter protein function to cause episodic inflammation is controv...

Apoptosis-associated speck-like protein containing a Caspase recruitment domain (ASC) belongs to a large family of proteins that contain a Pyrin, AIM, ASC, and death domain-like (PAAD) domain (also known as PYRIN, DAPIN, Pyk). Recent data have suggested that ASC functions as an adaptor protein linking various PAAD-family proteins to pathways involved in nuclear factor (NF)-kappaB and pro-Caspas...