PMID- 19781706
OWN - NLM
STAT- MEDLINE
DCOM- 20100604
LR  - 20220310
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Print)
IS  - 0021-9150 (Linking)
VI  - 209
IP  - 1
DP  - 2010 Mar
TI  - Anti-inflammatory effects of nicotinic acid in adipocytes demonstrated by 
      suppression of fractalkine, RANTES, and MCP-1 and upregulation of adiponectin.
PG  - 89-95
LID - 10.1016/j.atherosclerosis.2009.08.045 [doi]
AB  - OBJECTIVE: A major site of action for the atheroprotective drug nicotinic acid 
      (NA) is adipose tissue, via the G-protein-coupled receptor, GPR109A. Since, 
      adipose tissue is an active secretory organ that contributes both positively and 
      negatively to systemic inflammatory processes associated with cardiovascular 
      disease, we hypothesized that NA would act directly upon adipocytes to alter the 
      expression of pro-inflammatory chemokines, and the anti-inflammatory adipokine 
      adiponectin. METHODS AND RESULTS: TNF-alpha treatment (1.0ng/mL) of 3T3-L1 
      adipocytes resulted in an increase in gene expression of fractalkine 
      (9+/-3.3-fold, P<0.01); monocyte chemoattractant protein-1 (MCP-1) 
      (24+/-1.2-fold, P<0.001), 'regulated upon activation, normal T cell expressed and 
      secreted' (RANTES) (500+/-55-fold, P<0.001) and inducible nitric oxide synthase 
      (iNOS) (200+/-70-fold, P<0.05). The addition of NA (10(-4)M) to TNF-alpha-treated 
      adipocytes attenuated expression of fractalkine (50+/-12%, P<0.01); MCP-1 
      (50+/-6%, P<0.01), RANTES (70+/-3%, P<0.01) and iNOS (60+/-16%). This pattern was 
      mirrored in protein released from the adipocytes into the surrounding media. The 
      effect on gene expression was neutralised by pre-treatment with pertussis toxin. 
      NA attenuated macrophage chemotaxis (by 27+/-3.5%, P<0.001) towards adipocyte 
      conditioned media. By contrast, NA, (10(-6)-10(-3)M) increased, in a 
      dose-dependent manner, mRNA of the atheroprotective hormone adiponectin (3-5-fold 
      n=6, P<0.01). CONCLUSIONS: NA suppresses pro-atherogenic chemokines and 
      upregulates the atheroprotective adiponectin through a G-protein-coupled pathway. 
      Since adipose tissue has the potential to contribute to both systemic and local 
      (perivascular) inflammation associated with atherosclerosis our results suggest a 
      new "pleiotropic" role for NA.
FAU - Digby, Janet E
AU  - Digby JE
AD  - Department of Cardiovascular Medicine, University of Oxford, Oxford, United 
      Kingdom.
FAU - McNeill, Eileen
AU  - McNeill E
FAU - Dyar, Oliver J
AU  - Dyar OJ
FAU - Lam, Vincent
AU  - Lam V
FAU - Greaves, David R
AU  - Greaves DR
FAU - Choudhury, Robin P
AU  - Choudhury RP
LA  - eng
GR  - British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090831
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Adiponectin)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemokine CX3CL1)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 2679MF687A (Niacin)
SB  - IM
MH  - 3T3 Cells
MH  - Adipocytes/*drug effects/metabolism
MH  - Adiponectin/antagonists & inhibitors/metabolism
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Atherosclerosis/metabolism/*prevention & control
MH  - Chemokine CCL2/antagonists & inhibitors/metabolism
MH  - Chemokine CCL5/antagonists & inhibitors/metabolism
MH  - Chemokine CX3CL1/antagonists & inhibitors/metabolism
MH  - Culture Media, Conditioned/metabolism
MH  - Mice
MH  - Niacin/*pharmacology
MH  - Receptors, G-Protein-Coupled/antagonists & inhibitors/metabolism
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Up-Regulation
PMC - PMC2839075
EDAT- 2009/09/29 06:00
MHDA- 2010/06/05 06:00
PMCR- 2010/03/01
CRDT- 2009/09/29 06:00
PHST- 2009/05/19 00:00 [received]
PHST- 2009/08/06 00:00 [revised]
PHST- 2009/08/25 00:00 [accepted]
PHST- 2009/09/29 06:00 [entrez]
PHST- 2009/09/29 06:00 [pubmed]
PHST- 2010/06/05 06:00 [medline]
PHST- 2010/03/01 00:00 [pmc-release]
AID - S0021-9150(09)00707-2 [pii]
AID - 10.1016/j.atherosclerosis.2009.08.045 [doi]
PST - ppublish
SO  - Atherosclerosis. 2010 Mar;209(1):89-95. doi: 
      10.1016/j.atherosclerosis.2009.08.045. Epub 2009 Aug 31.