PMID- 25646371
OWN - NLM
STAT- MEDLINE
DCOM- 20150528
LR  - 20150306
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Linking)
VI  - 74
IP  - 4
DP  - 2015 Apr
TI  - Role of miR-146a in regulation of the acute inflammatory response to monosodium 
      urate crystals.
PG  - 786-90
LID - 10.1136/annrheumdis-2014-205409 [doi]
AB  - OBJECTIVES: MicroRNAs (miRNA) are small non-coding RNAs that function as 
      post-transcriptional repressors of gene expression. We hypothesised that miRNA 
      regulate gene expression of proinflammatory cytokines in response to monosodium 
      urate (MSU) crystals. METHODS: We stimulated human monocytic THP-1 cells with MSU 
      crystals and examined miRNA and proinflammatory cytokine gene expression. The 
      effects of miR-146a overexpression were examined by transfecting THP-1 cells with 
      miR-146a precursor. miR-146a expression was examined in the urate peritonitis 
      model, in peripheral blood mononuclear cells from people with gout and control 
      participants, and in gouty tophus samples. RESULTS: MSU crystals increased 
      miR-146a expression in THP-1 cells, but not other miRNA implicated in interleukin 
      (IL)-1beta regulation. Overexpression of miR-146a expression reduced MSU 
      crystal-induced IL-1beta, tumour necrosis factor-alpha (TNFalpha), monocyte chemoattractant 
      protein-1 (MCP-1) and IL-8 gene expression. In the urate peritonitis model, 
      reduced miR-146a expression was observed during the acute inflammatory response 
      to MSU crystal injection. In people with intercritical gout, peripheral blood 
      mononuclear cells expressed significantly higher levels of miR-146a, compared 
      with normouricaemic and hyperuricaemic control participants and those with acute 
      gout flares. Expression of miR-146a was also observed in all tophus samples. 
      CONCLUSIONS: Collectively, these data suggest that miR-146a is a transcriptional 
      brake that is lost during the acute inflammatory response to MSU crystals.
CI  - Published by the BMJ Publishing Group Limited. For permission to use (where not 
      already granted under a licence) please go to 
      http://group.bmj.com/group/rights-licensing/permissions.
FAU - Dalbeth, Nicola
AU  - Dalbeth N
AD  - Bone and Joint Research Group, Department of Medicine, University of Auckland, 
      Auckland, New Zealand.
FAU - Pool, Bregina
AU  - Pool B
AD  - Bone and Joint Research Group, Department of Medicine, University of Auckland, 
      Auckland, New Zealand.
FAU - Shaw, Odette M
AU  - Shaw OM
AD  - Malaghan Institute for Medical Research, Wellington, New Zealand.
FAU - Harper, Jacquie L
AU  - Harper JL
AD  - Malaghan Institute for Medical Research, Wellington, New Zealand.
FAU - Tan, Paul
AU  - Tan P
AD  - Bone and Joint Research Group, Department of Medicine, University of Auckland, 
      Auckland, New Zealand.
FAU - Franklin, Christopher
AU  - Franklin C
AD  - Bone and Joint Research Group, Department of Medicine, University of Auckland, 
      Auckland, New Zealand.
FAU - House, Meaghan E
AU  - House ME
AD  - Bone and Joint Research Group, Department of Medicine, University of Auckland, 
      Auckland, New Zealand.
FAU - Cornish, Jillian
AU  - Cornish J
AD  - Bone and Joint Research Group, Department of Medicine, University of Auckland, 
      Auckland, New Zealand.
FAU - Naot, Dorit
AU  - Naot D
AD  - Bone and Joint Research Group, Department of Medicine, University of Auckland, 
      Auckland, New Zealand.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150202
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (Antioxidants)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-8)
RN  - 0 (MIRN146 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 268B43MJ25 (Uric Acid)
SB  - IM
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Case-Control Studies
MH  - Cell Line
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression/drug effects
MH  - Gout/*genetics/metabolism
MH  - Humans
MH  - Hyperuricemia/genetics
MH  - Interleukin-1beta/metabolism
MH  - Interleukin-8/metabolism
MH  - Male
MH  - Mice
MH  - MicroRNAs/drug effects/*genetics
MH  - Monocytes/drug effects/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Uric Acid/pharmacology
OTO - NOTNLM
OT  - Cytokines
OT  - Gout
OT  - Inflammation
EDAT- 2015/02/04 06:00
MHDA- 2015/05/29 06:00
CRDT- 2015/02/04 06:00
PHST- 2015/02/04 06:00 [entrez]
PHST- 2015/02/04 06:00 [pubmed]
PHST- 2015/05/29 06:00 [medline]
AID - annrheumdis-2014-205409 [pii]
AID - 10.1136/annrheumdis-2014-205409 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2015 Apr;74(4):786-90. doi: 10.1136/annrheumdis-2014-205409. Epub 
      2015 Feb 2.