PMID- 22508334
OWN - NLM
STAT- MEDLINE
DCOM- 20130930
LR  - 20240322
IS  - 1476-5497 (Electronic)
IS  - 0307-0565 (Print)
IS  - 0307-0565 (Linking)
VI  - 37
IP  - 3
DP  - 2013 Mar
TI  - 1,25-Dihydroxyvitamin D3 inhibits the cytokine-induced secretion of MCP-1 and 
      reduces monocyte recruitment by human preadipocytes.
PG  - 357-65
LID - 10.1038/ijo.2012.53 [doi]
AB  - BACKGROUND: Adipose tissue expansion during obesity is associated with a state of 
      low-grade inflammation and an increase in macrophage infiltration, which 
      predisposes to insulin resistance and vascular malfunction. Growing evidence 
      suggests that vitamin D3 has immunoregulatory effects and adipose tissue could be 
      a target for vitamin D3 action. Preadipocytes, one of the major cell types in 
      adipose tissue, are actively involved in inflammatory processes. OBJECTIVES: This 
      study investigated whether the active form of vitamin D3 (1,25(OH)2D3) affects 
      the production of proinflammatory chemokines/cytokines and the monocyte 
      recruitment by human preadipocytes. METHODS/RESULTS: The secretion levels of 
      monocyte chemoattractant proteint-1 (MCP-1), IL-8 and IL-6 were significantly 
      higher in preadipocytes than in differentiated adipocytes, suggesting that 
      preadipocytes could be a major source of proinflammatory mediators. Cytokine 
      profile analysis revealed that 1,25(OH)2D3 (10 nM) markedly reduced the release 
      of MCP-1, IL-6 and IL-8 by preadipocytes. The involvement of NFkappaB signalling was 
      shown by the upregulation of IkappaBalpha protein abundance by 1,25(OH)2D3 in 
      preadipocytes. In addition, 1,25(OH)2D3 was able to decrease the migration of 
      THP-1 monocytes. Treatment with proinflammatory stimuli, including 
      macrophage-conditioned (MC) medium, TNFalpha and IL-1beta, led to a marked increase in 
      protein release of MCP-1 and IL-6 by preadipocytes. Pretreatment with 1,25(OH)2D3 
      (10 nM and 100 nM) significantly decreased the stimulatory effects of MC medium, 
      TNFalpha and IL-1beta on MCP-1 expression and protein release, although the effect on 
      stimulated release of IL-6 was less potent. CONCLUSIONS: These results 
      demonstrate that 1,25(OH)2D3 decreases the production of MCP-1 and other 
      proinflammatory mediators by preadipocytes and reduces monocyte migration. Thus, 
      vitamin D3 may protect against adipose tissue inflammation by disrupting the 
      deleterious cycle of macrophage recruitment.
FAU - Gao, D
AU  - Gao D
AD  - Obesity Biology Research Unit, Department of Obesity and Endocrinology, Institute 
      of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
FAU - Trayhurn, P
AU  - Trayhurn P
FAU - Bing, C
AU  - Bing C
LA  - eng
GR  - G0801226(87972)/MRC_/Medical Research Council/United Kingdom
GR  - G0801226/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120417
PL  - England
TA  - Int J Obes (Lond)
JT  - International journal of obesity (2005)
JID - 101256108
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (dihydroxy-vitamin D3)
RN  - 1406-16-2 (Vitamin D)
SB  - IM
MH  - Adipocytes/*drug effects/*metabolism
MH  - Adipose Tissue, White/*drug effects/immunology/metabolism
MH  - Adult
MH  - Blotting, Western
MH  - Cell Differentiation/drug effects
MH  - Chemokine CCL2/*antagonists & inhibitors/metabolism
MH  - Cytokines/*metabolism
MH  - Female
MH  - Humans
MH  - Inflammation/*drug therapy/immunology/metabolism
MH  - Inflammation Mediators/metabolism
MH  - Insulin Resistance/immunology
MH  - Interleukin-6/metabolism
MH  - Interleukin-8/metabolism
MH  - *Monocytes
MH  - NF-kappa B/metabolism
MH  - Obesity/*drug therapy/immunology/metabolism
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Vitamin D/*analogs & derivatives/pharmacology
PMC - PMC3428854
MID - UKMS47291
OID - NLM: UKMS47291
EDAT- 2012/04/18 06:00
MHDA- 2013/10/01 06:00
PMCR- 2013/09/01
CRDT- 2012/04/18 06:00
PHST- 2012/04/18 06:00 [entrez]
PHST- 2012/04/18 06:00 [pubmed]
PHST- 2013/10/01 06:00 [medline]
PHST- 2013/09/01 00:00 [pmc-release]
AID - ijo201253 [pii]
AID - 10.1038/ijo.2012.53 [doi]
PST - ppublish
SO  - Int J Obes (Lond). 2013 Mar;37(3):357-65. doi: 10.1038/ijo.2012.53. Epub 2012 Apr 
      17.