Article Text

SAT0385 Monosodium Urate Crystal-Induced Interleukin-1Beta Expression is Related to P62 Level in Autophagy Process
  1. S.-K. Kim1,
  2. J.-Y. Choe1,
  3. H. J. Kim2
  1. 1Division of Rheumatology, Department of Internal Medicine, Arthritis and Autoimmunity Research Center, Catholic University of Daegu School of Medicine, Daegu
  2. 2Division of Rheumatology, Department of Internal Medicine, Arthritis and Autoimmunity Research Center, Dong Kang General Hospital, Ulsan, Korea, Republic Of


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

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