MARCH3 attenuates IL-1β-triggered inflammation by mediating K48-linked polyubiquitination and degradation of IL-1RI.

ABSTRACT: The proinflammatory cytokine IL-1β plays critical roles in inflammatory and autoimmune diseases. IL-1β signaling is tightly regulated to avoid excessive inflammatory response. In this study, we identified the E3 ubiquitin ligase membrane-associated RING-CH-type finger 3 (MARCH3) as a critical negative regulator of IL-1β-triggered signaling. Overexpression of MARCH3 inhibited IL-1β-triggered activation of NF-κB as well as expression of inflammatory genes, whereas MARCH3 deficiency had the opposite effects. MARCH3-deficient mice produced higher levels of serum inflammatory cytokines and were more sensitive to inflammatory death upon IL-1β injection or Listeria monocytogenes infection. Mechanistically, MARCH3 was associated with IL-1 receptor I (IL-1RI) and mediated its K48-linked poly

SUBMITTER: Lin H 

PROVIDER: S-EPMC6298087 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature