SAT0385 Monosodium Urate Crystal-Induced Interleukin-1Beta Expression is Related to P62 Level in Autophagy Process

Objectives It has demonstrated that functional impairment of autophagy-related (Atg) genes including Atg16L1 and Atg5 enhanced interleukin-1b (IL-1b) expression response to monosodium urate (MSU) crystals. This study investigated whether process of autophagosome formation involved in IL-1b production in MSU crystal-induced inflammation Methods IL-1b, tumor necrosis factor-a (TNF-a), and IL-6 mRNA expressions were measured by quantitative real time-polymerase chain reaction (qRT-PCR). Expression for p62, Cullin-3, microtubule-associated protein 1 light-chain 3 (LC3)-I/II, ubiquitin, and mitogen-activated protein kinase (MAPK)-related proteins was measured by immunoblotting. This study used siRNAs for Atg16L1, IL-1b, and p62 for silencing each target gene. Results MSU crystals lead to accumulation of p62, which is related with suppression of proteasomal degradation, whereas MSU crystals itself induce LC3-II rather than LC3-I, implicating enhanced autophagosome formation. Enhanced p62 by MSU crystals results in IL-1b expression through ERK signal out of MAPK pathway. Impaired autophagosome formation by siRNA Atg16L1 enhanced more p62 levels and then amplified IL-1b expression. IL-1b also induces p62 protein, and IL-1b blockade reduced p62 levels. Conclusions This study demonstrated that MSU crystal-induced IL-1b expression might be related to p62 level through the regulation of proteasomal and autophagolysosomal degradation in autophagy process. It suggests that p62 could be a potent therapeutic target for gout inflammation. Disclosure of Interest None Declared