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The inflammasome is a potentially massive complex of proteins that assembles in response to a variety of intracellular danger signals. Once activated, inflammasomes catalyze the activation of the inflammatory cytokines IL-1β and IL-18, and they activate a cell death pathway called pyroptosis through the activation of a pore-forming protein called gasdermin D (GSDMD).
Inflammasomes are best studied in macrophages, but they are active in many other immune and non-immune cells. Likewise, IL-1β, IL-18, and pyroptosis are important in many different kinds of inflammatory responses.
Mutations in several proteins known to “nucleate” an inflammasome have been associated with autoinflammatory diseases. Foremost among these are MEFV, the gene associated with familial Mediterranean fever; NLRP3, the gene associated with neonatal onset multisystem inflammatory disease; and NLRC4, a gene associated with macrophage activation syndrome. Although mutations in any of these genes can cause increased inflammasome activation, the diseases are distinct.
This begs the question as to what makes these inflammasomes different. Our research team aims to leverage patient samples and various model systems to find out.
Spontaneous aggregation of ASC as a readout for inflammasome formation in an individual with NLRC4-associated macrophage activation syndrome.
Children's Hospital's main campus is located in the Lawrenceville neighborhood. Our main hospital address is:
Children’s Hospital of Pittsburgh of UPMC
One Children’s Hospital Way
4401 Penn Ave.
Pittsburgh, PA 15224
In addition to the main hospital, Children's has many convenient locations in other neighborhoods throughout the greater Pittsburgh region.
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