Identification of small-molecule elastase inhibitors as antagonists of IL-36 cytokine activation.

ABSTRACT: IL-1 family cytokines act as apical initiators of inflammation in many settings and can promote the production of a battery of inflammatory cytokines, chemokines and other inflammatory mediators in diverse cell types. IL-36α, IL-36β and IL-36γ, which belong to the extended IL-1 family, have been implicated as key initiators of skin inflammation in psoriasis. IL-36γ is highly upregulated in lesional skin from psoriatic individuals, and heritable mutations in the natural IL-36 receptor antagonist result in a severe form of psoriasis. IL-36 family cytokines are initially expressed as inactive precursors that require proteolytic processing for activation. The neutrophil granule-derived protease elastase proteolytically processes and activates IL-36α and IL-36γ, increasing their biological acti

SUBMITTER: Sullivan GP 

PROVIDER: S-EPMC5929933 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature