PMID- 27694988
OWN - NLM
STAT- MEDLINE
DCOM- 20180615
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Oct 3
TI  - Monosodium urate crystal-induced pro-interleukin-1beta production is 
      post-transcriptionally regulated via the p38 signaling pathway in human 
      monocytes.
PG  - 34533
LID - 10.1038/srep34533 [doi]
LID - 34533
AB  - IL-1beta 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 well-known role of sterile particulates 
      such as monosodium urate (MSU) crystals as inflammasome inducers in 
      monocytes/macrophages, little is known regarding how pro-IL-1beta synthesis is 
      induced under sterile inflammatory conditions. We provide evidence that MSU 
      crystals post-transcriptionally induce the rapid production of pro-IL-1beta 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-1beta as well as global proteins. Notably, MSU crystal-induced 
      pro-IL-1beta 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-1beta synthesis downstream of eIF4E phosphorylation. In addition, the p38 
      MAPK pathway leading to phosphorylation of MK2 was also critical for 
      stabilization of pro-IL-1beta 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-1beta in response to MSU crystals, which is an 
      essential step for IL-1beta production in human monocytes.
FAU - Chung, Yeon-Ho
AU  - Chung YH
AD  - Department of Biomedical Sciences, and BK21Plus Biomedical Science Project, Seoul 
      National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, 
      South Korea.
FAU - Kim, Dong-Hyun
AU  - Kim DH
AD  - Department of Biomedical Sciences, and BK21Plus Biomedical Science Project, Seoul 
      National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, 
      South Korea.
FAU - Lee, Won-Woo
AU  - Lee WW
AD  - Department of Biomedical Sciences, and BK21Plus Biomedical Science Project, Seoul 
      National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, 
      South Korea.
AD  - Department of Microbiology and Immunology, Seoul National University College of 
      Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, South Korea.
AD  - Cancer Research Institute, Ischemic/Hypoxic Disease Institute, and Institute of 
      Infectious Diseases, Seoul National University College of Medicine; Seoul 
      National University Hospital Biomedical Research Institute, 103 Daehak-ro, 
      Jongno-gu, Seoul 110-799, South Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161003
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Interleukin-1)
RN  - 0 (Protein Precursors)
RN  - 0 (interleukin 1 precursor)
RN  - 268B43MJ25 (Uric Acid)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Female
MH  - Humans
MH  - Interleukin-1/*biosynthesis
MH  - MAP Kinase Signaling System/*drug effects
MH  - Male
MH  - Monocytes/*metabolism
MH  - Protein Precursors/*biosynthesis
MH  - Uric Acid/*pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
PMC - PMC5046103
EDAT- 2016/10/04 06:00
MHDA- 2018/06/16 06:00
PMCR- 2016/10/03
CRDT- 2016/10/04 06:00
PHST- 2016/04/14 00:00 [received]
PHST- 2016/09/15 00:00 [accepted]
PHST- 2016/10/04 06:00 [entrez]
PHST- 2016/10/04 06:00 [pubmed]
PHST- 2018/06/16 06:00 [medline]
PHST- 2016/10/03 00:00 [pmc-release]
AID - srep34533 [pii]
AID - 10.1038/srep34533 [doi]
PST - epublish
SO  - Sci Rep. 2016 Oct 3;6:34533. doi: 10.1038/srep34533.