PMID- 19563447
OWN - NLM
STAT- MEDLINE
DCOM- 20100416
LR  - 20090923
IS  - 1365-2362 (Electronic)
IS  - 0014-2972 (Linking)
VI  - 39
IP  - 10
DP  - 2009 Oct
TI  - Fatty acids as metabolic mediators in innate immunity.
PG  - 924-33
LID - 10.1111/j.1365-2362.2009.02185.x [doi]
AB  - BACKGROUND: Increasing data support the hypothesis of a local and systemic 
      crosstalk between adipocytes and monocytes mediated by fatty acids. The aim of 
      this study was to characterize the immunomodulatory effects of a large panel of 
      fatty acids on cytokines and chemokines in monocytic THP-1 cells and primary 
      human monocytes. We tested whether anti-inflammatory fatty acids are able to 
      inhibit the binding of lipopolysaccharide (LPS) to its receptor, toll-like 
      receptor/MD-2 (TLR4/MD-2). MATERIALS AND METHODS: Resistin, monocyte 
      chemoattractant protein-1 (MCP-1) and tumour necrosis factor (TNF) were measured 
      by enzyme-linked immunosorbent assay. Proteins were analysed by Western blot. A 
      designed Flag-tagged TLR4/MD-2 fusion protein (LPS trap) was used to investigate 
      the effect of fatty acids on binding of LPS to its receptor. In 30 patients with 
      type 2 diabetes mellitus (T2D), the correlation of serum triglyceride levels with 
      LPS-induced monocyte activation was analysed. RESULTS: Eleven fatty acids 
      investigated exerted differential effects on the monocytic release of cytokines 
      and chemokines. Eicosapentaenoic acid had potent anti-inflammatory effects on 
      human primary monocytes and THP-1 cells; 100 and 200 microM eicosapentaenoic acid 
      dose-dependently inhibited LPS binding to the LPS trap. LPS-induced release of 
      monocytic MCP-1 and TNF was significantly and positively correlated with serum 
      triglyceride levels in 30 patients with T2D. CONCLUSIONS: Monocytic activation is 
      differentially regulated by fatty acids and depends on triglyceride levels in 
      T2D. The main finding of the present study shows that eicosapentaenoic acid 
      inhibits the specific binding of LPS to TLR4/MD-2. Eicosapentaenoic acid 
      represents a new anti-inflammatory LPS-antagonist.
FAU - Kopp, A
AU  - Kopp A
AD  - Regensburg University Hospital, Regensburg, Germany.
FAU - Gross, P
AU  - Gross P
FAU - Falk, W
AU  - Falk W
FAU - Bala, M
AU  - Bala M
FAU - Weigert, J
AU  - Weigert J
FAU - Buechler, C
AU  - Buechler C
FAU - Neumeier, M
AU  - Neumeier M
FAU - Scholmerich, J
AU  - Scholmerich J
FAU - Schaffler, A
AU  - Schaffler A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090626
PL  - England
TA  - Eur J Clin Invest
JT  - European journal of clinical investigation
JID - 0245331
RN  - 0 (Chemokine CCL2)
RN  - 0 (Fatty Acids)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Lymphocyte Antigen 96)
RN  - 0 (Resistin)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adipocytes/drug effects/metabolism
MH  - Blotting, Western
MH  - Chemokine CCL2/*metabolism/pharmacology
MH  - Diabetes Mellitus, Type 2/*immunology
MH  - Fatty Acids/*metabolism
MH  - Female
MH  - Humans
MH  - Immunity, Innate/*immunology
MH  - Lipopolysaccharides/metabolism
MH  - Lymphocyte Antigen 96/metabolism
MH  - Male
MH  - Middle Aged
MH  - Monocytes/drug effects/metabolism
MH  - Resistin/*metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism/pharmacology
EDAT- 2009/07/01 09:00
MHDA- 2010/04/17 06:00
CRDT- 2009/07/01 09:00
PHST- 2009/07/01 09:00 [entrez]
PHST- 2009/07/01 09:00 [pubmed]
PHST- 2010/04/17 06:00 [medline]
AID - ECI2185 [pii]
AID - 10.1111/j.1365-2362.2009.02185.x [doi]
PST - ppublish
SO  - Eur J Clin Invest. 2009 Oct;39(10):924-33. doi: 10.1111/j.1365-2362.2009.02185.x. 
      Epub 2009 Jun 26.