Effect of activated platelets on expression of cytokines in peripheral blood mononuclear cells - potential role of prostaglandin E2.
Platelets may act as inflammatory cells. To study the effects of soluble and cell-bound platelet factors on the expression of several cytokines and related mediators in leukocytes, peripheral blood mononuclear cells (PBMC) were incubated with platelet-free supernatants from SFLLRN-activated platelet-rich plasma (PRP) or SFLLRN-activated PRP in itself. Our main findings were: (i) the gene expression of several chemokines and some cytokines were markedly increased by both activated PRP and supernatants, as also confirmed at the protein level for IL-6, IL-8 and MIP-1alpha; (ii) the selective protein kinase A type I (PKAI) antagonist Rp-8-Br-cAMP reduced this platelet-induced expression of IL-6, IL-8 and MIP-1alpha in PBMC, suggesting a role of cAMP/PKAI mediated mechanisms in this interaction; (iii) PGE(2) dose-dependently increased the release of IL-6, IL-8 and MIP-1alpha from PBMC mimicking the effect of activated platelets. Furthermore, activated platelets released comparable amounts of PGE(2), suggesting that platelet-derived PGE2 could interact with PBMC in co-cultures; (iv) IL-10 inhibited the platelet-inducing effect on IL-6, IL-8 and MIP-1alpha in PBMC, and notably, the addition PGE2 totally abolished this IL-10 effect suggesting that the suppressive effect of IL-10 on the plateletinduced activation of PBMC might at least partly involve PGE(2) related mechanisms. The present study supports a view of platelets as inflammatory cells, and suggests a potential role of platelet-derived PGE(2) in platelet-induced inflammatory responses.
Waehre
Torgun
T
Research Institute of Internal Medicine, Rikshospitalet University Hospital, N-0027 Oslo, Norway.
Damås
Jan Kristian
JK
Yndestad
Arne
A
Taskén
Kjetil
K
Pedersen
Turid M
TM
Smith
Camilla
C
Halvorsen
Bente
B
Frøland
Stig S
SS
Solum
Nils O
NO
Aukrust
Pål
P
D000328:Adult; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines / Q000096:biosynthesis*; D018076:DNA, Complementary / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation; D016753:Interleukin-10 / Q000378:metabolism / Q000502:physiology; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015539:Platelet Activation; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines; D018076:DNA, Complementary; D015850:Interleukin-6; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D016753:Interleukin-10; D015232:Dinoprostone