title: Effect of activated platelets on expression of cytokines in peripheral blood mononuclear cells - potential role of prostaglandin E2.
abstract: 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.
authors.affiliation: Research Institute of Internal Medicine, Rikshospitalet University Hospital, N-0027 Oslo, Norway.
authors.forename: Torgun
authors.initials: T
authors.lastname: Waehre
authors.forename: Jan Kristian
authors.initials: JK
authors.lastname: Damås
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.forename: Kjetil
authors.initials: K
authors.lastname: Taskén
authors.forename: Turid M
authors.initials: TM
authors.lastname: Pedersen
authors.forename: Camilla
authors.initials: C
authors.lastname: Smith
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.forename: Stig S
authors.initials: SS
authors.lastname: Frøland
authors.forename: Nils O
authors.initials: NO
authors.lastname: Solum
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
mesh_terms: 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
chemical_list: 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