Immunomodulating effects of 3-thia fatty acids in activated peripheral blood mononuclear cells.
BACKGROUND
3-thia fatty acids such as tetradecylthioacetic acid (TTA) are modified fatty acids that have been suggested to change the plasma profile from atherogenic to cardio protective. Because of its interaction with peroxisome proliferator activated receptor (PPAR) we hypothesized that TTA also could have immunomodulatory properties. Based on the suggested role of inflammation in atherogenesis, any immunomodulating effects of TTA would be of particular interest for the potential use of this fatty acid in atherosclerotic disorders.


METHODS
We examined if TTA could modulate proliferation and the release of cytokines from peripheral mononuclear cells (PBMCs) taken from five healthy blood donors.


RESULTS
Our main findings were: (i) TTA had several effects on cytokine release from activated PBMCs with a marked increase in interleukin (IL)-10 accompanied by a reduction in IL-2 possibly favouring anti-inflammatory net effects. (ii) These cytokine-modifying effects were found in both T cells and monocytes when cultured separately. (iii) Tetradecylthioacetic acid increased the cytokine stimulating effects of tumour necrosis factor alpha with a particularly enhancing effect on IL-10. (iv) Tetradecylthioacetic acid significantly suppressed PBMC proliferation, and this antiproliferative property did not involve enhanced apoptosis or necrosis. (v) These immunomodulatory effects of TTA were accompanied by a marked down-regulation of PPARoad mRNA expression, the most abundant PPAR subtype in PBMCs.


CONCLUSIONS
Our findings show potent immunomodulatory effects of TTA in activated PBMCs, possibly involving PPAR-related mechanisms.
Aukrust
P
P
Section of Clinical Immunology and Infectious Diseases, Research Institute for Internal Medicine, Rikshospitalet, Oslo, Norway.
Wergedahl
H
H
Müller
F
F
Ueland
T
T
Dyrøy
E
E
Damås
J K
JK
Frøland
S S
SS
Berge
R K
RK
D000328:Adult; D017209:Apoptosis / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013440:Sulfides / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D016207:Cytokines; D007376:Interleukin-2; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C062078:1-(carboxymethylthio)tetradecane