Journal
CELL DEATH AND DIFFERENTIATION
Volume 13, Issue 2, Pages 236-249Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cdd.4401734
Keywords
inflammation; inflammasome; pyrin; cryopyrin; caspase-1; ASC; interleukin-1 beta; NF-kappa B
Categories
Funding
- NIA NIH HHS [AG14357, AG13487] Funding Source: Medline
Ask authors/readers for more resources
Mutations in cryopyrin and pyrin proteins are responsible for several autoinflammatory disorders in humans, suggesting that these proteins play important roles in regulating inflammation. Using a HEK293 cell-based reconstitution system that stably expresses ASC and procaspase-1 we demonstrated that neither cryopyrin nor pyrin or their corresponding disease-associated mutants could significantly activate NF-kappa B in this system. However, both cryopyrin and two disease-associated cryopyrin mutants induced ASC oligomerization and ASC-dependent caspase-1 activation, with the disease-associated mutants being more potent than the wild-type (WT) cryopyrin, because of increased self-oligomerization. Contrary to the proposed anti-inflammatory activity of WT pyrin, our results demonstrated that pyrin, like cryopyrin, can also assemble an inflammasome complex with ASC and procaspase-1 leading to ASC oligomerization, caspase-1 activation and interleukin-1 beta processing. Thus, we propose that pyrin could function as a proinflammatory molecule.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available