Shedding of the type II IL-1 decoy receptor requires a multifunctional XXXX , @entity2965 regulator of TNF receptor type 1 shedding.

@entity10732 @entity1356 @entity8460 @entity4515 @entity10496 @entity10497 @entity1360 @entity2965
Proteolytic cleavage of the extracellular domain of the type II IL-1 decoy receptor ( @entity10732 ) generates soluble IL-1-binding proteins that prevent excessive bioactivity by binding free IL-1. In this study we report that an @entity2965 , @entity8460 ( @entity8460 ), is required for @entity10732 shedding. Coimmunoprecipitation experiments demonstrate an association between endogenous membrane-associated @entity8460 and a 47-kDa @entity10732 , consistent with ectodomain cleavage of the membrane-bound receptor. A direct correlation exists between @entity8460 protein expression and @entity10732 shedding, as cell lines overexpressing @entity8460 have increased @entity10732 shedding and decreased membrane-associated @entity10732 . Basal @entity10732 shedding is absent from @entity8460 knockout cell lines, demonstrating that @entity8460 is required for constitutive @entity10732 shedding. Similarly, @entity4515 -mediated @entity10732 shedding is almost entirely @entity8460 -dependent. @entity8460 expression also enhances @entity1360 -induced @entity10732 shedding. @entity8460 did not alter levels of membrane-associated IL-1RI or @entity10496 antagonist release from @entity8460 cell lines, which suggests that the ability of @entity8460 to promote shedding of @entity10496 family members may be specific for @entity10732 . Further, increased @entity10732 shedding by @entity8460 -overexpressing cells attenuates the biological activity of @entity1356 . We conclude that the ability of @entity8460 to enhance @entity10732 shedding represents a new mechanism by which IL-1-induced cellular events can be modulated. As @entity8460 also promotes the shedding of the structurally unrelated 55-kDa, type I TNF receptor and the @entity10497 , we propose that @entity8460 may play an important role in regulating innate immune and inflammatory responses by increasing cytokine receptor shedding.
