Scientific Reports | 6:34533

 

Monosodium urate crystal-induced pro-interleukin-1β production is post-transcriptionally regulated via the p38 signaling pathway in human monocytes

Yeon-Ho Chung, Dong-Hyun Kim & Won-Woo Lee

 

Abstract

IL-1β is a key mediator of sterile inflammation in response to endogenous particulates, a type of
damage-associated molecular pattern (DAMPs) molecule derived from damaged cells. Despite the wellknown
role of sterile particulates such as monosodium urate (MSU) crystals as inflammasome inducers
in monocytes/macrophages, little is known regarding how pro-IL-1β synthesis is induced under sterile
inflammatory conditions. We provide evidence that MSU crystals post-transcriptionally induce the
rapid production of pro-IL-1β in human primary monocytes. Metabolic labeling and pull-down assays
for newly-synthesized proteins clearly showed that MSU crystals rapidly, within 30 min, induce the
synthesis of pro-IL-1β as well as global proteins. Notably, MSU crystal-induced pro-IL-1β synthesis is
selectively dependent on the p38 MAPK pathway, whereas global protein synthesis is mediated via
the mTOR, ERK1/2, and p38 pathways. Furthermore, inhibition of Mnk1, a substrate of p38, blocked
MSU crystal-induced pro-IL-1β synthesis downstream of eIF4E phosphorylation. In addition, the p38
MAPK pathway leading to phosphorylation of MK2 was also critical for stabilization of pro-IL-1β mRNA
following MSU stimulation. Our findings demonstrate that post-transcriptional regulation via p38
MAPK plays a central role in the rapid synthesis of pro-IL-1β in response to MSU crystals, which is an
essential step for IL-1β production in human monocytes.