PMID- 24831058
OWN - NLM
STAT- MEDLINE
DCOM- 20150123
LR  - 20140918
IS  - 1462-0332 (Electronic)
IS  - 1462-0324 (Linking)
VI  - 53
IP  - 10
DP  - 2014 Oct
TI  - The effect of diet-induced obesity on the inflammatory phenotype of 
      non-adipose-resident macrophages in an in vivo model of gout.
PG  - 1901-5
LID - 10.1093/rheumatology/keu174 [doi]
AB  - OBJECTIVE: Gout is strongly associated with obesity. The aim of this study was to 
      determine if obesity altered the inflammatory phenotype of non-adipose 
      tissue-resident macrophages in response to the gout-causing agent monosodium 
      urate (MSU) crystals. METHODS: C57BL/6J mice were fed a high-fat diet for 12 
      weeks. Resident peritoneal macrophages were stimulated ex vivo with MSU crystals 
      (200 microg/ml for 18 h) and the supernatants were collected. Mice were challenged 
      with MSU crystals in vivo (3 mg, intraperitonal) and the peritoneal lavage fluid 
      was collected (8 and 16 h). Cytokine and chemokine levels were analysed by 
      multiplex bead array and peritoneal cell populations were analysed by flow 
      cytometry. RESULTS: Peritoneal macrophages from obese mice produced elevated 
      background levels of IL-6, monocyte chemoattractant protein 1 (MCP-1) and 
      keratinocyte-derived cytokine (KC) that decreased following MSU crystal 
      stimulation ex vivo. MSU-induced IL-1beta production was higher for macrophages from 
      obese mice compared with controls. High background levels of IL-6, MCP-1, KC and 
      GM-CSF, but not IL-1beta, were measured in the peritoneal fluid of unchallenged 
      obese mice. MSU crystal challenge in vivo raised IL-1beta levels equally in both 
      control and obese mice, whereas elevated background levels of IL-6, MCP-1, KC and 
      GM-CSF levels dropped in obese mice. There was a consistent trend towards lower 
      numbers of naive peritoneal resident macrophages and MSU-recruited monocytes and 
      neutrophils in obese mice. CONCLUSION: Obesity induces a background 
      pro-inflammatory environment orchestrated by non-adipose tissue-resident 
      macrophages. However, this may not automatically translate into exacerbation of 
      MSU crystal-induced inflammation in gout.
CI  - (c) The Author 2014. Published by Oxford University Press on behalf of the British 
      Society for Rheumatology. All rights reserved. For Permissions, please email: 
      journals.permissions@oup.com.
FAU - Shaw, Odette M
AU  - Shaw OM
AD  - Arthritis and Inflammation Group, Malaghan Institute of Medical Research, 
      Wellington and Bone and Joint Research Group, Department of Medicine, Faculty of 
      Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
FAU - Pool, Bregina
AU  - Pool B
AD  - Arthritis and Inflammation Group, Malaghan Institute of Medical Research, 
      Wellington and Bone and Joint Research Group, Department of Medicine, Faculty of 
      Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
FAU - Dalbeth, Nicola
AU  - Dalbeth N
AD  - Arthritis and Inflammation Group, Malaghan Institute of Medical Research, 
      Wellington and Bone and Joint Research Group, Department of Medicine, Faculty of 
      Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
FAU - Harper, Jacquie L
AU  - Harper JL
AD  - Arthritis and Inflammation Group, Malaghan Institute of Medical Research, 
      Wellington and Bone and Joint Research Group, Department of Medicine, Faculty of 
      Medical and Health Sciences, University of Auckland, Auckland, New Zealand. 
      jharper@malaghan.org.nz.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140515
PL  - England
TA  - Rheumatology (Oxford)
JT  - Rheumatology (Oxford, England)
JID - 100883501
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 147037-79-4 (keratinocyte-derived chemokines)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/metabolism
MH  - Chemokines/metabolism
MH  - *Diet, High-Fat
MH  - Disease Models, Animal
MH  - Gout/complications/*metabolism/pathology
MH  - Inflammation/metabolism/pathology
MH  - Interleukin-1beta/metabolism
MH  - Interleukin-6/metabolism
MH  - Macrophages/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Obesity/complications/*metabolism/pathology
OTO - NOTNLM
OT  - cytokines
OT  - gout
OT  - inflammation
OT  - metabolic syndrome
OT  - monocytes
OT  - neutrophils
OT  - obesity
OT  - resident macrophages
EDAT- 2014/05/17 06:00
MHDA- 2015/01/24 06:00
CRDT- 2014/05/17 06:00
PHST- 2014/05/17 06:00 [entrez]
PHST- 2014/05/17 06:00 [pubmed]
PHST- 2015/01/24 06:00 [medline]
AID - rheumatology/keu174 [pii]
AID - 10.1093/rheumatology/keu174 [doi]
PST - ppublish
SO  - Rheumatology (Oxford). 2014 Oct;53(10):1901-5. doi: 10.1093/rheumatology/keu174. 
      Epub 2014 May 15.