Peroxisome proliferator-activated receptor alpha, delta, gamma1 and gamma2 expressions are present in human monocyte-derived dendritic cells and modulate dendritic cell maturation by addition of subtype-specific ligands.
It has recently been shown by Chang et al. (J Immunol 2000;165:3584-91) that the maturation of dendritic cells (DC) in the presence of long-chain fatty acids redirects DC into Th0/Th2-inducing cells suggesting the involvement of a receptor for long-chain fatty acids like members of the peroxisome proliferator-activated receptors (PPAR) superfamily. Here, we show that immature and mature monocyte-derived DC (Mo-DC) express PPARalpha, PPARdelta, PPARgamma1 and PPARgamma2 mRNA with the highest level of PPARgamma1 mRNA. We were only able to observe the expression of PPARgamma1 protein by Western blotting probably because the protein level of the other subtypes is below the detection limit. Synthetic ligands specific for PPARalpha, PPARdelta or PPARgamma added at day 0-6 have similar effect on the maturation of Mo-DC driving the maturation of Mo-DC with atypical phenotype, reduced expression of IL-10, IL-12 p35 and IL-12 p40 mRNA and with reduced stimulatory effects in mixed leucocyte reaction (MLR). Our data suggest that naturally occurring PPAR ligands like fatty acids and fatty acid derivates have anti-inflammatory effects by redirecting DC into a less stimulatory mode.
Jakobsen
M A
MA
Department of Clinical Immunology, Odense University Hospital, Odense, Denmark. marianne.jakobsen@ouh.fyns-amt.dk
Petersen
R K
RK
Kristiansen
K
K
Lange
M
M
Lillevang
S T
ST
D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation; D005227:Fatty Acids / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D008024:Ligands; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000166:cytology; D047493:PPAR alpha / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D047494:PPAR delta / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism
D005227:Fatty Acids; C508858:IL12A protein, human; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D008024:Ligands; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D021122:Protein Subunits; D016753:Interleukin-10; D018664:Interleukin-12